Displaying One Session

Cordoba Auditorium (Hall 7) Poster Discussion session
Date
29.09.2019
Time
16:30 - 17:45
Location
Cordoba Auditorium (Hall 7)
Chairs
  • Fiona H. Blackhall (Manchester, United Kingdom)
  • Ross Soo (Singapore, Singapore)
  • Federico Cappuzzo (Ravenna, Italy)
Poster Discussion – NSCLC, metastatic Poster Discussion session

1483PD - Pembrolizumab (pembro) plus platinum-based chemotherapy (chemo) in NSCLC with brain metastases: Pooled analysis of KEYNOTE-021, 189, and 407 (ID 4597)

Presentation Number
1483PD
Lecture Time
16:30 - 16:30
Speakers
  • Steven F. Powell (Sioux Falls, United States of America)
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
16:30 - 17:45

Abstract

Background

Historically, pts with NSCLC and brain metastases have had poor prognosis. Randomized studies have shown OS and PFS benefit and manageable safety with pembro plus chemo vs chemo alone in pts with advanced NSCLC. We present a pooled analysis of outcomes in pts with NSCLC and stable brain metastases at baseline who were enrolled in randomized clinical trials evaluating pembro plus platinum-based chemo as first-line therapy for advanced/metastatic NSCLC.

Methods

This post hoc analysis pooled data for pts with stable, treated or untreated brain metastases from KEYNOTE-021 cohort G (nonsquamous; NCT02039674), 189 (nonsquamous; NCT02578680), and 407 (squamous; NCT02775435). Pts were randomly assigned to platinum-doublet chemo (pemetrexed-carboplatin/cisplatin for nonsquamous NSCLC and carboplatin-paclitaxel/nab-paclitaxel for squamous NSCLC) with/without pembro; KEYNOTE-189 and 407 were placebo-controlled. Response (systemic, including in brain) was assessed per RECIST v1.1 by blinded, independent central review.

Results

Of 1298 pts included, 171 (13%) had baseline brain metastases. Median (range) follow-up was 10.9 (0.1–35.1) mo and 11.0 (0.1–34.9) mo in pts with and without brain metastases, respectively. HRs for OS and PFS were improved with pembro plus chemo vs chemo irrespective of baseline brain metastasis status (Table). ORR was higher and duration of response (DOR) was longer with pembro plus chemo vs chemo alone. All-cause grade 3–5 AEs with pembro plus chemo vs chemo alone occurred in 81.4% vs 70.3% of pts with brain metastases and 68.3% vs 65.6% without brain metastases.

1483PD

NOS HR (95% CI)PFS HR (95% CI)ORR, %Median DOR, mo (range)
Brain metastasesPembro plus chemo1050.48 (0.32–0.70)0.44 (0.31–0.62)39.011.3 (1.1+ to 27.9+)
Chemo6619.76.8 (1.3+ to 9.4)
No brain metastasesPembro plus chemo6430.63 (0.53–0.75)0.55 (0.48–0.63)54.612.2 (1.1+ to 29.3+)
Chemo48431.86.0 (1.4+ to 30.1+)

, response ongoing at data cutoff.

Conclusions

Pembro plus chemo provided clinical benefit for pts with NSCLC pts, regardless of presence/absence of stable brain metastases. The toxicity profile was manageable. Pembro plus chemo is standard of care therapy for pts with advanced NSCLC, including those with baseline brain metastases.

Clinical trial identification

NCT02039674; NCT02578680; NCT02775435.

Editorial acknowledgement

Rozena Varghese, PharmD, of C4 MedSolutions, LLC (Yardley, PA, USA), a CHC Group company, funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

S.F. Powell: Research grant / Funding (institution): Merck; Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Vyriad; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Novartis. D. Rodriguez Abreu: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Speaker Bureau / Expert testimony: Roche. C.J. Langer: Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): OSI (Astellas); Research grant / Funding (institution): Merck; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Nektar; Research grant / Funding (institution): Advantage; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): Inovio; Research grant / Funding (institution): Ariad; Research grant / Funding (institution): StemCentrx; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Guardant Health; Advisory / Consultancy: Merck; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Bayer/Onyx; Advisory / Consultancy: Abbott; Advisory / Consultancy: Morphotek; Advisory / Consultancy: Biodesix; Advisory / Consultancy: Clarient; Advisory / Consultancy: Caris Diagnostics; Advisory / Consultancy: Vertex; Advisory / Consultancy: Synta Pharmaceuticals; Advisory / Consultancy: Celgene; Advisory / Consultancy: Boehringer-Ingelheim; Advisory / Consultancy: Hospira; Advisory / Consultancy: Helsinn; Advisory / Consultancy: Synta Pharmaceuticals; Advisory / Consultancy: Clovis; Advisory / Consultancy: Ariad (Takeda); Advisory / Consultancy: Takai; Advisory / Consultancy: Regeneron;Officer / Board of Directors (data and safety monitoring committee member): Eli Lilly; Officer / Board of Directors (data and safety monitoring committee member): Amgen; Officer / Board of Directors (data and safety monitoring committee member): Synta Pharmaceuticals; Officer / Board of Directors (data and safety monitoring committee member): Agennix; Officer / Board of Directors (data and safety monitoring committee member): SWOG; Officer / Board of Directors (data and safety monitoring committee member): Peregrine Pharmaceuticals; Officer / Board of Directors (data and safety monitoring committee member): Incyte; Speaker Bureau / Expert testimony (CME presenter): PIK; Speaker Bureau / Expert testimony (CME presenter): PER; Speaker Bureau / Expert testimony (CME presenter): NOCR; Speaker Bureau / Expert testimony (CME presenter): Imedex; Speaker Bureau / Expert testimony (CME presenter): CCO; Speaker Bureau / Expert testimony (CME presenter): RTP; Speaker Bureau / Expert testimony (CME presenter): MLG; Speaker Bureau / Expert testimony (CME presenter): TRM; Speaker Bureau / Expert testimony (CME presenter): Web-MD. L. Paz-Ares: Honoraria (self), Spouse / Financial dependant: Roche; Honoraria (self), Spouse / Financial dependant: Lilly; Honoraria (self), Spouse / Financial dependant: Boehringer Ingelheim; Honoraria (self), Spouse / Financial dependant: AstraZeneca; Honoraria (self), Spouse / Financial dependant: Novartis; Honoraria (self), Spouse / Financial dependant: Pfizer; Honoraria (self), Spouse / Financial dependant: Amgen; Honoraria (self), Spouse / Financial dependant: BMS; Honoraria (self), Spouse / Financial dependant: MSD; Honoraria (self), Spouse / Financial dependant: Merck; Honoraria (self), Spouse / Financial dependant: Sanofi; Honoraria (self), Spouse / Financial dependant: PharmaMar; Honoraria (self), Spouse / Financial dependant: Servier; Honoraria (self), Spouse / Financial dependant: Sysmex; Honoraria (self), Spouse / Financial dependant: Incyte; Honoraria (self), Spouse / Financial dependant: Ipsen; Honoraria (self), Spouse / Financial dependant: Adacap; Honoraria (self), Spouse / Financial dependant: Bayer; Honoraria (self), Spouse / Financial dependant: Blueprint Medicines; Honoraria (self), Spouse / Financial dependant: Celgene; Officer / Board of Directors: Genómica; Research grant / Funding (institution): MSD; Research grant / Funding (institution): BMS; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Pfizer. H. Kopp: Honoraria (self), Travel / Accommodation / Expenses: MSD; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Travel / Accommodation / Expenses: Sanofi; Honoraria (self): Roche; Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Amgen. J. Rodríguez-Cid: Research grant / Funding (institution): MSD; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Celgene. D. Kowalski: Research grant / Funding (institution): MSD. Y. Cheng: Research grant / Funding (institution): MSD. T. Kurata: Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self): Eli Lilly; Honoraria (self): Chugai; Honoraria (self): Ono; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim. M.M. Awad: Advisory / Consultancy: Merck. J. Lin: Full / Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. B. Zhao: Full / Part-time employment: Merck Sharp & Dohme Corp. M.C. Pietanza: Full / Part-time employment: Merck Sharp & Dohme Corp. B. Piperdi: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck Sharp & Dohme Corp. M.C. Garassino: Honoraria (self), Research grant / Funding (institution): Merck; Honoraria (self), Research grant / Funding (institution): BMS; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): Celgene; Honoraria (self), Research grant / Funding (institution): MedImmune; Honoraria (self): Incyte; Honoraria (self): Ignyta. All other authors have declared no conflicts of interest.

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Poster Discussion – NSCLC, metastatic Poster Discussion session

LBA82 - Pembrolizumab (pembro) + chemotherapy (chemo) in metastatic squamous NSCLC: Final analysis and progression after the next line of therapy (PFS2) in KEYNOTE-407 (ID 4134)

Presentation Number
LBA82
Lecture Time
16:30 - 16:30
Speakers
  • Luis Paz-Ares (Madrid, Spain)
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
16:30 - 17:45

Abstract

Background

In the randomized KEYNOTE-407 study (NCT02775435), pembro + carboplatin and paclitaxel/nab-paclitaxel (chemo) significantly improved OS, PFS, and ORR compared with placebo + chemo in patients (pts) with previously untreated metastatic squamous NSCLC. Benefit was observed irrespective of PD-L1 TPS. We report updated OS from the protocol-specified final analysis and, for the first time, PFS2.

Methods

Eligible pts were randomized 1:1 to pembro (n = 278) or placebo (n = 281) + 4 cycles of carboplatin and paclitaxel/nab-paclitaxel. Randomization was stratified by PD-L1 TPS (≥1%/<1%), choice of taxane (paclitaxel/nab-paclitaxel), and region (East Asia/rest of world). Pts in the placebo + chemo arm could crossover to pembro monotherapy at the time of confirmed PD. After positive results from IA2, pts on the placebo arm were unblinded to stop placebo. Response was assessed by RECIST v1.1 by blinded central review. Primary endpoints were OS and PFS. PFS2 was an exploratory endpoint and defined as time from randomization to time of PD per investigator or death after start of 2L therapy, whichever occurred first.

Results

With median follow-up of 14.3 mo (range, 0.1–31.3) and 365 total deaths, pembro + chemo continued to improve OS (median [95% CI], 17.1 [14.4–19.9] vs 11.6 [10.1–13.7] mo), PFS (median [95% CI], 8.0 [6.3–8.4] vs 5.1 [4.3–6.0]; Table) and ORR (62.6% vs 38.4%). 2L+ therapy was received by 32.0% in the pembro + chemo arm and 59.4% (49.1% 2L+ antiPD[L]1) in the placebo + chemo arm. PFS2 was longer for 1L pembro + chemo (median [95% CI], 13.8 [12.2–15.9] mo vs 9.1 [8.2–10.2] mo), with no difference by PD-L1 TPS.

LBA82

All Patients N = 559PD-L1 TPS ≥50% N = 146PD-L1 TPS 1–49% N = 207PD-L1 TPS <1% N = 194
OS, HR (95% CI)0.71 (0.58–0.88)0.79 (0.52–1.21)0.59 (0.42–0.84)0.79 (0.56–1.11)
PFS, HR (95% CI)0.57 (0.47–0.69)0.43 (0.29–0.63)0.52 (0.38–0.71)0.67 (0.49–0.91)
PFS2, HR (95% CI)0.59 (0.49–0.72)0.61 (0.40–0.91)0.51 (0.37–0.72)0.61 (0.44–0.85)

Conclusions

Pembro + chemo continued to demonstrate improved outcomes, including OS, PFS, ORR and PFS2, compared with placebo + chemo for previously untreated metastatic squamous NSCLC, with a manageable safety profile. These results support first-line pembro + chemo in pts with metastatic squamous NSCLC.

Clinical trial identification

NCT02775435.

Editorial acknowledgement

Writing support was provided by Sheri Arndt, PharmD, of C4 MedSolutions, LLC (Yardley, PA, USA), a CHC Group company, funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

L. Paz-Ares: Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Roche; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Lilly; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Boehringer Ingelheim; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: AstraZeneca; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Novartis; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Pfizer; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Amgen; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: BMS; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: MSD; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Merck; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Sanofi; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: PharmaMar; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Servier; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Sysmex; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Incyte; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Ipsen; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Adacap; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Bayer; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Blueprint Medicines; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Celgene; Honoraria to self/spouse for scientific advice or as a speaker for Roche, Lilly, Boehringer Ingelheim, AstraZeneca, Novartis, Pfizer, Amgen, BMS, MSD, Merck, Sanofi, PharmaMar, Servier, Sysmex, Incyte, Ipsen, Adacap, Bayer, Blueprint Medicines, and Celgene; board member for Genómica; grants to institution from MSD, BMS, AstraZeneca, and Pfizer. D. Vicente: Honoraria (self), Self/spouse for scientific advice or as a speaker: Boehringer Ingelheim, AstraZeneca, Pfizer, BMS, and MSD . A. Robinson: Research grant / Funding (institution), funding for clinical trials: Merck, AstraZeneca, Roche, and Pfizer; Advisory / Consultancy: Merck. H. Soto Parra: Advisory / Consultancy: AstraZeneca, MSD, BMS, Roche, and Eli Lilly. J. Mazières: Honoraria (institution): Roche, AstraZeneca, Boehringer Ingelheim, Pfizer, BMS, MSD, Merck, Pierre Fabre, PharmaMar, Bayer, and Blueprint; Research grant / Funding (institution): Roche, MSD, BMS, and AstraZeneca. B. Hermes: Travel / Accommodation / Expenses: PharmaMar and Eli Lilly; Honoraria (institution), honoraria for lectures: BMS and Pfizer; Research grant / Funding (institution): MSD, Novartis, BMS, Bayer, Roche, Eli Lilly, and PharmaMar. I. Cicin: Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, F. Hoffmann-La Roche, and Pfizer; Research grant / Funding (self), personal fees for lectures: Eli Lilly, MSD, Novartis, Pfizer, Quintiles, and Roche; Research grant / Funding (institution), funding to the institution to support trial conduct: Astellas, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Parexel, Pfizer, Quintiles, Taiho, and Merck Serono. J. Rodríguez Cid: Research grant / Funding (institution), funding to the institution during conduct of this trial: MSD; Research grant / Funding (institution), funding to the institution to support trial conduct: Bayer, BMS, Celgene, Eli Lilly, MSD, Novartis, and Roche. I. Okamoto: Research grant / Funding (self), grants and personal fees: AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, MSD Oncology, Eli Lilly, BMS, Chugai Pharma; Research grant / Funding (self), personal fees : Pfizer; Research grant / Funding (institution), grants: Astellas Pharma, Novartis, and AbbVie. R. Ramlau: Honoraria (self), honoraria to self/spouse for scientific advice or as a speaker: Roche, Eli Lilly, Boehringer Ingelheim, AstraZeneca, Novartis, Pfizer, Amgen, BMS, MSD, Merck, and Sanofi; Officer / Board of Directors, board member: Boehringer Ingelheim, Pfizer, MSD, BMS, Novartis, Takeda, AbbVie, AstraZeneca, Eli Lilly, and Roche. X. Deng: Full / Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.. T. Bas: Full / Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.. B. Piperdi: Full / Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.. B. Halmos: Research grant / Funding (institution): Merck, BMS, Boehringer Ingelheim, Eli Lilly, Novartis, GSK, Pfizer, AbbVie, AstraZeneca, Mirati, Takeda, and Guardant Health; Advisory / Consultancy, consultant : Merck, Novartis, Boehringer Ingelheim, AstraZeneca, Novartis, Pfizer, Guardant Health, Spectrum, BMS, and Genentech. All other authors have declared no conflicts of interest.

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Poster Discussion – NSCLC, metastatic Poster Discussion session

LBA83 - Final efficacy results from B-F1RST, a prospective phase II trial evaluating blood-based tumour mutational burden (bTMB) as a predictive biomarker for atezolizumab (atezo) in 1L non-small cell lung cancer (NSCLC) (ID 2239)

Presentation Number
LBA83
Lecture Time
16:30 - 16:30
Speakers
  • Mark Socinski (Orlando, PA, United States of America)
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
16:30 - 17:45

Abstract

Background

bTMB assays determine TMB using a noninvasive blood test. B-F1RST (ITT, n = 152) is the first prospective trial to evaluate bTMB as a biomarker to predict benefit of 1L atezo monotherapy in advanced NSCLC. bTMB high (score of ≥ 16; ≥ 14.5 mut/Mb) predicted better ORR with atezo vs bTMB low (< 16; 28.6% vs 4.4%) in the biomarker evaluable population (BEP) with ≥ 6 mo follow up in the primary analysis. Numerical benefit for bTMB high was seen in median (m)PFS and mOS. Here we report the B-F1RST final analysis.

Methods

Eligibility criteria included untreated stage IIIB-IVB NSCLC and ECOG PS 0/1. Pts received atezo 1200 mg IV q3w until PD, intolerance or loss of benefit. Co-primary endpoints were investigator assessed ORR for efficacy (ITT) and PFS for biomarker analysis (BEP) at a prespecified bTMB cutoff of 16 for high (≥ 16) vs low (< 16). PFS and OS, a secondary endpoint, were further evaluated at various bTMB cutoffs. Serum C-reactive protein (CRP), an inflammation marker in cancer, was evaluated as a surrogate biomarker, ratio of CRP at C3D1 to CRP at screening, to predict PFS and OS.

Results

With ≥ 18 mo follow up (data cutoff, 14 May 2019) in ITT pts, ORR was 17% (95% CI: 12, 24), mPFS was 4.1 mo (95% CI: 2.8, 4.9) and mOS was 14.8 mo (95% CI: 12.7, 21.3). In bTMB ≥ 16 vs < 16, mPFS was 5.0 vs 3.5 mo and mOS was 23.9 vs 13.4 mo (Table). For CRP ratio < 0.5 vs ≥ 0.5, mPFS was 14.1 vs 4.6 mo (HR, 0.43 [90% CI: 0.24, 0.77]), and mOS was NE vs 15.9 mo (HR, 0.30 [90% CI: 0.13, 0.72]). 14% of pts had treatment-related (TR) serious AEs, and 20% had Gr 3-4 TRAEs. 18% of pts had AEs that led to discontinuation.

LBA83

PFS results
Median (95% CI), mo
ITT (N = 152)4.1 (2.8, 4.9)
BEP (n = 119)bTMB High (≥ bTMB cutoff)bTMB Low (< bTMB cutoff)HR90% CI
bTMB cutoffMedian, mo (n)Median, mo (n)
122.6 (44)4.1 (75)1.160.83, 1.64
165.0 (28)3.5 (91)0.800.54, 1.18
206.9 (19)2.9 (100)0.590.37, 0.93
OS results
Median (95% CI), mo
ITT (N = 152)14.8 (12.7, 21.3)
BEP (n = 119)bTMB High (≥ bTMB cutoff)bTMB Low (< bTMB cutoff)HR90% CI
bTMB cutoffMedian, mo (n)Median, mo (n)
1215.7 (44)13.8 (75)0.950.62, 1.46
1623.9 (28)13.4 (91)0.660.40, 1.10
2023.9 (19)13.1(100)0.440.23, 0.85

Conclusions

B-F1RST shows the clinical utility of bTMB as a predictive biomarker for pts receiving 1L atezo monotherapy. The final analysis confirmed that pts with bTMB ≥ 16 had numerical benefit for PFS and OS. Decrease in serum CRP over 6 wk predicted PFS and OS benefit. No new safety signals were seen.

Clinical trial identification

NCT02848651.

Editorial acknowledgement

Medical writing assistance was provided by Chris Lum, PhD, of Health Interactions, and funded by F. Hoffmann-La Roche, Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche, Ltd.

Funding

F. Hoffmann-La Roche, Ltd.

Disclosure

M. Socinski: Research grant / Funding (institution), Non-remunerated activity/ies: F. Hoffmann-La Roche. V. Velcheti: Advisory / Consultancy, Speaker Bureau / Expert testimony: Genentech, Inc.; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Foundation Medicine. T. Mekhail: Speaker Bureau / Expert testimony: Roche/Genentech. Y.K. Chae: Advisory / Consultancy: Foundation Medicine; Advisory / Consultancy: Guardant Health; Advisory / Consultancy: Biodesix; Honoraria (self): F. Hoffmann La Roche; Honoraria (self): AstraZeneca; Honoraria (self): Merck; Research grant / Funding (institution): BMS. T.A. Leal: Advisory / Consultancy: Genentech, Inc.; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Advisory / Consultancy: Bayer; Travel / Accommodation / Expenses, Non-remunerated activity/ies: Mirati Therapeutics. J.E. Dowell: Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Trizell. V. Shen: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche/Genentech. S. Hu: Full / Part-time employment: Genentech, Inc.. S.M. Paul: Full / Part-time employment: Genentech, Inc.. D.S. Shames: Full / Part-time employment: Genentech, Inc.. E. Schleifman: Full / Part-time employment: Genentech, Inc.. D.A. Fabrizio: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine, Inc. M. Nowicki: Shareholder / Stockholder / Stock options, Full / Part-time employment: F. Hoffmann-La Roche. C. Yun: Full / Part-time employment: Genentech, Inc.. S. Phan: Full / Part-time employment: Genentech, Inc.. E.S. Kim: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Takeda. All other authors have declared no conflicts of interest.

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Poster Discussion – NSCLC, metastatic Poster Discussion session

LBA84 - Primary results from TAIL, a global single-arm safety study of atezolizumab (atezo) monotherapy in a diverse population of patients with previously treated advanced non-small cell lung cancer (NSCLC) (ID 2584)

Presentation Number
LBA84
Lecture Time
16:30 - 16:30
Speakers
  • Andrea Ardizzoni (Bologna, Italy)
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
16:30 - 17:45

Abstract

Background

Atezo treatment (tx) has demonstrated improved survival and a manageable safety in advanced NSCLC. TAIL (NCT03285763) is a phase III/IV study evaluating the safety and efficacy of atezo in patients (pts) with previously treated advanced NSCLC, including those who are generally excluded from pivotal trials.

Methods

TAIL enrolled pts with Stage IIIb/IV NSCLC who experienced disease progression after 1-2 lines of standard chemotherapy. Eligible subgroups included prior anti–PD-1 therapy, ECOG PS 2, renal impairment and pre-existing autoimmune disease. Atezo was given at 1200 mg IV q3w. The primary endpoint is safety as measured by the incidences of treatment-related (TR) serious AEs (SAEs) and TR immune-related AEs (irAEs). Secondary endpoints are OS and PFS, ORR and duration of response (DOR) per investigator assessment.

Results

Of the 619 pts enrolled between Oct 2017 and Dec 2018, 615 received atezo. Median age was 64 y, 60% of pts were male and 90% had ECOG PS 0/1. At data cutoff (4 Jun 2019), median follow-up was 12.7 mo (95% CI 11.9, 13.1); 133 pts (21.5%) remained on tx and 316 pts (51.1%) had died. Co-primary endpoints: TR SAEs occurred in 7.8% of pts and TR irAEs occurred in 8.3% (Table). Median OS was 11.1 mo (95% CI 8.9, 12.9), ORR was 11.1% (95% CI 8.7, 13.8) and median DOR was 14.6 mo (95% CI 8.4, 15.4). In a subgroup of pts similar to those in the phase III OAK study (n = 406), mOS was 13.7 mo (95% CI 11.6, 15.5), ORR was 13.6% (95% CI 10.4, 17.3) and mDOR was 14.6 mo (95% CI 7.7, NE). Safety and efficacy data in subgroups, including PD-L1 expression, prior anti–PD-1 therapy, ECOG PS 2, renal impairment and autoimmune disease will be presented.

LBA84

All pts N = 615
Median treatment duration (range), mo3.2 (0–18.6)
TR SAE, n (%)48 (7.8)
TR irAE, n (%)51 (8.3)
Most common any-grade TR SAEs (in ≥ 3 pts), n (%)
Pneumonitis10 (1.6)
Infusion-related reaction5 (0.8)
Pyrexia4 (0.7)
Colitis3 (0.5)
Pericarditis3 (0.5)
Most common any-grade TR irAEs (in ≥ 3 pts), n (%)
Pneumonitis18 (2.9)
Hypothyroidism7 (1.1)
Rash7 (1.1)
Colitis4 (0.7)
Hyperthyroidism4 (0.7)

Conclusions

TAIL confirmed the safety profile of atezo monotherapy in a diverse, previously treated NSCLC population. The safety and efficacy data may inform treatment decisions for pts generally excluded from pivotal trials.

Clinical trial identification

NCT03285763.

Editorial acknowledgement

Medical writing assistance for this abstract was provided by Kia C. E. Walcott, PhD, of Health Interactions, and funded by F. Hoffmann-La Roche, Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche, Ltd.

Funding

F. Hoffmann-La Roche, Ltd.

Disclosure

A. Ardizzoni: Honoraria (self): Eli-Lilly; Honoraria (self): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: MSD; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: AstraZeneca; Research grant / Funding (institution): Celgene. S. Azevedo: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Celgene; Honoraria (self), Research grant / Funding (institution): Lilly; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: MSD. D. Rodriguez Abreu: Full / Part-time employment: Insular University Hospital in Gran Canaria, Spain; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca. J. Alatorre-Alexander: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck-Sharp & Domme; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Leadership role: Head of Oncology in National Institute of Respiratory Diseases Mexico ; Full / Part-time employment: Medical oncologist National Institute of Respiratory Diseases. H.J. Smit: Advisory / Consultancy: MSD; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Leadership role: Secretary section oncology NVALT (Dutch lung phycisions organasation); Leadership role: president DLCA (Dutch Lung Cancer Audit). K. Syrigos: Speaker Bureau / Expert testimony: MSD; Research grant / Funding (institution): ROCHE; Research grant / Funding (institution): NOVARTIS; Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: GENESIS. H. Patel: Full / Part-time employment: Genentech/Roche. J. Tolson: Full / Part-time employment: Roche. A. Cardona: Honoraria (institution), Full / Part-time employment: F. Hoffmann-La Roche . P. Perez Moreno: Full / Part-time employment: Roche/Genentech. T. Newsom-Davis: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZenca,; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS,; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eli Lilly,; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD,; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Otsuka,; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche,; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Takeda; Advisory / Consultancy: Amgen,; Advisory / Consultancy: Pfizer,; Leadership role: Vice-Chair, British Thoracic Oncology Group. All other authors have declared no conflicts of interest.

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Poster Discussion – NSCLC, metastatic Poster Discussion session

Invited Discussant 1483PD, LBA82, LBA83 and LBA84 (ID 6910)

Lecture Time
16:30 - 16:45
Speakers
  • Federico Cappuzzo (Ravenna, Italy)
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
16:30 - 17:45
Poster Discussion – NSCLC, metastatic Poster Discussion session

Q&A led by Discussant (ID 6915)

Lecture Time
16:45 - 16:55
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
16:30 - 17:45
Poster Discussion – NSCLC, metastatic Poster Discussion session

1484PD - Final PFS, updated OS and safety data from the randomised, phase III ALEX study of alectinib (ALC) versus crizotinib (CRZ) in untreated advanced ALK+ NSCLC (ID 3850)

Presentation Number
1484PD
Lecture Time
16:55 - 16:55
Speakers
  • Tony S.K. Mok (Shatin, Hong Kong PRC)
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
16:30 - 17:45

Abstract

Background

We report mature PFS, updated OS and safety data from the global phase III ALEX study (NCT02075840) of ALC vs CRZ in patients (pts) with untreated ALK+ NSCLC after a further 12 months (m) of follow-up (cutoff date: 30 Nov 2018).

Methods

Eligible pts had stage IIIB/IV ALK+ NSCLC (by central IHC), ECOG PS 0–2 and no prior systemic therapy for advanced NSCLC. Asymptomatic CNS metastases (mets) were allowed. Pts were randomised 1:1 to twice-daily ALC 600mg (n = 152) or CRZ 250mg (n = 151). Primary endpoint: investigator (INV)-assessed PFS (RECIST v1.1), with q8w CNS imaging in all pts.

Results

Mature, median INV-assessed PFS: 34.8 m (95% CI 17.7–NR) ALC vs 10.9 m (95% CI 9.1–12.9) CRZ (ITT stratified HR 0.43, 95% CI 0.32–0.58; p < 0.0001); pts with event, 53.3% ALC vs 80.8% CRZ. Median duration of follow-up: 37.8 m ALC vs 23.0 m CRZ. Median INV-assessed PFS was longer with ALC vs CRZ in pts with baseline (BL) CNS mets (25.4 m vs 7.4 m, respectively, HR 0.37, 95% CI 0.23–0.58) and in those without (38.6 m vs 14.8 m, respectively, HR 0.46, 95% CI 0.31–0.68). PFS event-free rate was higher with ALC vs CRZ regardless of BL CNS mets status, with 43.7% of ALC pts event-free at 4 years (Table). OS data remain immature (events: 32%; stratified HR 0.69, 95% CI 0.47–1.02). OS in pts with CNS mets at BL, HR 0.60 (95% CI 0.34–1.05) and in pts without CNS mets at BL, HR 0.77 (95% CI 0.45–1.32). The 4-year OS rate was 64.5% (95% CI 55.6–73.4) with ALC vs 52.2% (95% CI 42.6–64.8) with CRZ. Despite longer median treatment duration with ALC vs CRZ (27.7 m vs 10.8 m), the safety profile for ALC remains favourable; fewer ALC-treated pts experienced grade 3–5 AEs (48.7% vs 55.0% CRZ).

1484PD

PFS event-free rate, % (95% CI)
OS event-free rate, % (95% CI)
ALC (n = 152)
CRZ (n = 151)
ALC (n = 152)CRZ (n = 151)
Duration (years)OverallBaseline CNS mets
OverallBaseline CNS mets
OverallOverall
YesNoYesNo
167.8 (60.3–75.3)58.574.548.0 (39.7–56.2)32.557.284.3 (78.4–90.2)82.5 (76.1–88.9)
256.6 (48.6–64.6)52.059.824.8 (17.6–32.1)6.335.772.5 (65.1–79.9)65.1 (56.7–73.4)
346.4 (38.2–54.5)40.550.613.5 (7.7–19.3)2.120.266.9 (59.0–74.8)56.7 (47.8–65.6)
443.7 (35.4–51.9)38.047.6NE (NE–NE)NENE64.5 (55.6–73.4)52.2 (42.6–61.8)

NE, not estimable

Conclusions

This final updated PFS analysis confirms the superior efficacy and favourable tolerability of ALC compared with CRZ in pts with untreated ALK+ NSCLC. OS data remain immature (stratified HR 0.69, 95% CI 0.47–1.02), with a 4-year OS rate of 64.5% (95% CI 55.6–73.4) with ALC.

Clinical trial identification

NCT02075840.

Editorial acknowledgement

Nicola Griffin of Gardiner-Caldwell Communications; funded by F. Hoffmann-La Roche.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

T.S.K. Mok: Leadership role: Sanonics Ltd.; Honoraria (self), Advisory / Consultancy: ACEA Biosciences, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Chimed, Cirina, Fishawack Facilitate, Ignyta, Janssen, Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, OncoGenex, Pfizer, F. Hoffmann-La Roche Ltd/Genentech, SFJ Pharm; Research grant / Funding (self): AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Merck Sharp & Dohme, Novartis, Pfizer, F. Hoffmann-La Roche Ltd, SFJ Pharmaceutical and XCovery. A.T. Shaw: Honoraria (self), Advisory / Consultancy: F. Hoffmann-La Roche Ltd, Genentech, Pfizer, Novartis, Ariad, Ignyta, Daiichi-Sankyo, Taiho, Blueprint medicines, LOXO, EMD Serono and Foundation medicine. R.D. Camidge: Honoraria (self), Advisory / Consultancy: AbbVie, Ariad, Array, Celgene, Clovis Oncology, Eli Lilly, Genoptix, G1 Therapeutics, Novartis, Orion, and F. Hoffmann-La Roche Ltd/Genentech. S.M. Gadgeel: Honoraria (self), Advisory / Consultancy: Ariad, AstraZeneca, Bristol-Myers Squibb, Pfizer and F. Hoffmann-La Roche Ltd/Genentech. R. Dziadziuszko: Honoraria (self), Advisory / Consultancy: F. Hoffmann-La Roche Ltd, Pfizer, Boehringer Ingelheim, Clovis Oncology, Novartis, AstraZeneca and Tesaro. D. Kim: Travel / Accommodation / Expenses: F. Hoffmann-La Roche Ltd, Pfizer, Boehringer Ingelheim, Clovis Oncology, Novartis, AstraZeneca and Tesaro; Travel / Accommodation / Expenses: Novartis Oncology; Research grant / Funding (institution): Alpha Biopharma, AstraZeneca/MedImmune, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery and Yuhan. M. Perol: Honoraria (self), Advisory / Consultancy: F. Hoffmann-La Roche Ltd/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, Clovis Oncology, Merck Sharp & Dohme, Chugai, Bristol-Myers Squibb, Amgen, Novartis, Pierre Fabre, AstraZeneca, Takeda ; Research grant / Funding (institution): F. Hoffmann-La Roche Ltd, AstraZeneca, Chugai and Takeda. S. Ou: Honoraria (self): ARIAD, AstraZeneca, Pfizer, F. Hoffmann-La Roche Ltd/Genentech and TP Therapeutics; Speaker Bureau / Expert testimony: ARIAD, AstraZeneca and F. Hoffmann-La Roche Ltd/Genentech; Research grant / Funding (self): ARIAD, AstraZeneca, Daiichi Sankyo, Pfizer and F. Hoffmann-La Roche Ltd/Genentech; Shareholder / Stockholder / Stock options: TP Therapeutics. W. Bordogna: Full / Part-time employment: F. Hoffmann-La Roche Ltd. V. Smoljanović: Full / Part-time employment: F. Hoffmann-La Roche Ltd. M. Hilton: Full / Part-time employment: F. Hoffmann-La Roche Ltd. S. Peters: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche Ltd, Foundation Medicine, Illumina, Janssen, Merck Sharp and Dohme, Merck Serono, Merrimack, Nova. All other authors have declared no conflicts of interest.

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Poster Discussion – NSCLC, metastatic Poster Discussion session

1485PD - Safety and efficacy of WX-0593 in ALK-positive or ROS1-positive non-small cell lung cancer (ID 6131)

Presentation Number
1485PD
Lecture Time
16:55 - 16:55
Speakers
  • Yuan-Kai Shi (Beijing, China)
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
16:30 - 17:45

Abstract

Background

WX-0593 is a potent ALK inhibitor against ALK and ROS1 rearrangement and a series of crizotinib (CRZ)-resistant mutants. We explored the safety and efficacy of WX-0593 in patients (pts) diagnosed with ALK+ or ROS-1+ malignancies, including non-small cell lung cancer (NSCLC).

Methods

In this ongoing phase I, dose-escalation, multicenter trial (NCT03389815), 54 pts (third-grade class-A hospital confirmed ALK+ or ROS-1+) received WX-0593 (30, 60, 90, 120, 180, 240 or 300 mg) orally once daily until disease progression or unacceptable toxicity. Activity and safety were evaluated.

Results

From 25 September 2017 to 26 December 2018, 54 pts were enrolled, including 46 with ALK+ NSCLC, 10 with ROS1+ NSCLC (2 with both ALK+ and ROS1+, 38.9% with prior CRZ, 9.3% with prior CRZ and second generation ALK inhibitors). Grade 3 QTc prolongation reported in 300 mg cohort was identified as dose-limiting toxicity (DLT). Treatment-emergent adverse events (TAEs) associated with WX-0593 in > 20% of pts include: hypercholesterolemia (40.7%), nausea (40.7%), hypertension (37.0%) increased ALT (31.5%), increased AST (29.6%), hypertriglyceridemia (25.9%), hyperlipidemia (25.9%), vomiting 25.9%. Serious adverse events (SAE) occurred in 6 pts (11.1%). No treatment related death occurred. 2 pts (3.7%) had SAE related with WX-0593 treatment, including increased ALT (dose of 180 mg), increased AST (dose of 180 mg) and chronic heart failure (dose of 300 mg). For ALK+ NSCLC (n=46), objective response rate (ORR) was 29/44 (65.9%). The ORR in CRZ-naive pts was 17/21 (81.0%), 8/18 (44.4%) in CRZ pre-treated pts. ORR was 3/10 (30.0%) in ROS1+ NSCLC pts. By 26 December 2018, median progression-free survival was not reached, 39 patients remained on WX0593 treatment.

1485PD Objective response rate in ALK-positive and ROS1-positive NSCLC patients

ORR, n / m (%)30mg N = 360mg N = 390mg N = 8120mg N = 11180mg N = 13240mg N = 13300mg N = 3total
ALK+NSCLC
all pts2/2 (100.0)2/3 (66.7)2/5 (40.0)8/10 (80.0)7/10 (70.0)7/11 (63.6)1/3 (33.3)29/44 (65.9)
CRZ-naive pts2/2 (100.0)2/3 (66.7)06/7 (85.7)3/4 (75.0)3/4 (75.0)1/1 (100.0)17/21 (81.0)
pts with prior CRZ002/4 (50.0)1/2 (50.0)3/5 (60.0)2/5 (40.0)0/28/18 (44.4)
pts with prior CRZ and other ALK inhibitor000/11/1 (100.0)1/1 (100.0)2/2 (100.0)04/5 (80.0)
ROS1+NSCLC
all pts0/101/3 (33.3%)0/12/3 (66.7%)0/203/10 (30.0%)

Conclusions

This study revealed the antitumor activity of WX-0593 in ALK- or ROS-positive NSCLC. Safety profile was acceptable. A phase II trial to evaluate the ORR of 120 mg and 180 mg once daily is ongoing.

Clinical trial identification

NCT03389815.

Legal entity responsible for the study

Qilu Pharmaceutical Co., Ltd.

Funding

Qilu Pharmaceutical Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.

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Poster Discussion – NSCLC, metastatic Poster Discussion session

1486PD - Exposure-response analyses of ALK-inhibitors crizotinib and alectinib in NSCLC patients (ID 1906)

Presentation Number
1486PD
Lecture Time
16:55 - 16:55
Speakers
  • Steffie L. Groenland (Amsterdam, Netherlands)
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
16:30 - 17:45

Abstract

Background

Crizotinib and alectinib are first and second generation ALK-inhibitors, respectively, indicated for the treatment of ALK+ NSCLC. At the currently used fixed doses, interpatient variability in exposure is high (40%), while the registration studies suggest that exposure might be linked to efficacy (FDA Reviews). Therefore, the aim of this study was to explore whether exposure to crizotinib and alectinib is related to efficacy in a real life patient (pt) cohort.

Methods

A retrospective observational study was performed. ALK+ NSCLC pts who were treated with crizotinib or alectinib and of whom pharmacokinetic (PK) samples were drawn as part of routine care were included. Calculated minimum plasma concentration (Cmin) was taken as a measure of exposure. Efficacy endpoint was progression free survival (PFS). Univariable and multivariable exposure-response analyses were performed using previously proposed thresholds of 235 µg/L for crizotinib and 435 µg/L for alectinib (Verheijen 2017). Variables taken into account were WHO performance status (PS) and previous lines of therapy for crizotinib, and WHO PS and previous treatment with ALK-inhibitors for alectinib.

Results

In total, 100 pts were included in this study (48 crizotinib, 52 alectinib), of whom 376 PK samples were eligible for analysis (235 crizotinib, 141 alectinib). Median number of samples per pt was 3 (range 1 – 15). Median Cmin per pt was 244 µg/L (IQR 176 – 344 µg/L) for crizotinib and 517 µg/L (IQR 369 – 659 µg/L) for alectinib. For crizotinib, median PFS was 5.7 vs 17.4 months (mo) for pts with median Cmin < 235 µg/L (48%) and ≥ 235 µg/L, respectively (log rank test, p = 0.08). In multivariable analysis Cmin < 235 µg/L resulted in a HR of 1.79 (95% CI 0.90 – 3.59, p = 0.10). For alectinib, median PFS was 12.6 mo vs not reached yet after 20 mo for pts with Cmin < 435 µg/L (37%) and ≥ 435 µg/L, respectively (log rank test, p = 0.04). Multivariable analysis resulted in a HR of 3.86 (95% CI 1.19 – 12.58, p = 0.025). Thus far, this could not be explained by bias.

Conclusions

This study shows that exposure to alectinib is associated with efficacy in a real life patient cohort. Therefore, therapeutic drug monitoring might be appropriate to individualize treatment and improve treatment outcomes.

Legal entity responsible for the study

Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital.

Funding

Has not received any funding.

Disclosure

S.A. Burgers: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche Advisory / Consultancy: MSD. N. Steeghs: Research grant / Funding (institution): AstraZeneca/MedImmune; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): AB Science; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Merck Sharp & Dohme; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Merus; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Incyte. All other authors have declared no conflicts of interest.

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Poster Discussion – NSCLC, metastatic Poster Discussion session

1487PD - Intracranial and extracranial efficacy of lorlatinib in the post second-generation ALK tyrosine kinase inhibitor (TKI) setting (ID 2577)

Presentation Number
1487PD
Lecture Time
16:55 - 16:55
Speakers
  • D. Ross Camidge (Aurora, CO, United States of America)
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
16:30 - 17:45

Abstract

Background

The selective, potent, brain-penetrant 3rd-generation (gen) ALK TKI lorlatinib is approved for the treatment of patients (pts) with ALK+ metastatic non-small cell lung cancer (NSCLC) whose disease has progressed following 2nd-gen ALK TKIs.

Methods

In this ongoing ph 2 study (NCT01970865), 139 pts with ALK+ advanced NSCLC with ≥1 prior 2nd-gen ALK TKI, ± chemotherapy (CT), were enrolled in expansion cohorts—EXP3B, EXP4 and EXP5—based on treatment history. Overall, intracranial (IC) and extracranial (EC) antitumor activity were assessed by independent central review, per modified RECIST v1.1. Recurrent event analysis on within-patient time to progression (TTP) was conducted comparing TTP on lorlatinib with TTP on the last prior 2nd-gen ALK TKI.

Results

Of the 139 pts with ≥1 prior 2nd-gen ALK TKI (EXP3B–5), 28 had 1 prior 2nd-gen ALK TKI as their only ALK TKI (EXP3B), 65 had 2 prior ALK TKIs (EXP4) and 46 had 3 prior ALK TKIs (EXP5). As of data cutoff (02 Feb 2018), the ORR in EXP3B–5 was 40% (95% CI 32–49), median duration of response (DOR) was 7.1 mo (95% CI 5.6–24.4) and median PFS was 6.9 mo (95% CI 5.4–8.2). Responses were observed in pts who had also received prior CT (n/N=40/93; ORR 43% [95% CI 33–54]) as well as in CT-naïve pts (n/N=16/46; ORR 35% [95% CI 21–50]). IC- and EC-ORR in EXP3B–5 and individual cohorts are shown in the table. In EXP3B–5, median IC DOR was 12.4 mo (95% CI 5.8–NR) and median EC DOR was 9.7 mo (95% CI 6.1–NR). Based on 121 evaluable pts, no significant differences were observed in terms of TTP between lorlatinib and last prior 2nd-gen ALK TKI (HR 0.86, 95% CI 0.64–1.16).

1487PD

IC ORR
EC ORR
N*% (95% CI)N% (95% CI)
EXP3B–55754 (41–68)13937 (29–46)
EXP3B967 (30–93)2832 (16–52)
EXP42458 (37–78)6538 (27–51)
EXP52446 (26–67)4639 (25–55)

Patients with ≥1 measurable CNS metastases at baseline

EC, extracranial; IC, intracranial; ORR, objective response rate

Conclusions

In the post 2nd-gen ALK TKI setting, lorlatinib showed clinically meaningful antitumor activity in both IC and EC compartments, with a trend towards elevated IC vs EC ORR particularly in pts with fewer lines of therapy. Despite pts having a worse prognosis at a later line, lorlatinib showed a similar TTP compared with the last 2nd-gen ALK TKI.

Clinical trial identification

NCT01970865.

Editorial acknowledgement

Jade Drummond of inScience Communications, Springer Healthcare, Chester, UK; funded by Pfizer Inc.

Legal entity responsible for the study

Pfizer Inc.

Funding

Pfizer Inc.

Disclosure

D.R. Camidge: Honoraria (self): Roche; Honoraria (self): G1 Therapeutics; Honoraria (self): Mersana; Honoraria (self), Research grant / Funding (self): Takeda; Honoraria (self): AstraZeneca; Honoraria (self): Genoptix; Honoraria (self): Ignyta; Honoraria (self): Daiichi Sankyo; Honoraria (self): Hansoh; Honoraria (self): Lycera; Honoraria (self): Biothera; Honoraria (self): Revolution Medicines. B.J. Solomon: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Eisai; Licensing / Royalties: Veristrat (Biodesix); Licensing / Royalties: UpToDate; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Merck; Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Institution: Merck Sharp & Dohme; Advisory / Consultancy, Research grant / Funding (institution), Institution: Pfizer; Advisory / Consultancy, Institution: Genentech. E. Felip: Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy: Celgene; Advisory / Consultancy: Guardant Health; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: AbbVie; Advisory / Consultancy: Blueprint Medicines; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Dohme; Research grant / Funding (institution): Fundación Merck Salud; Research grant / Funding (institution): EMD Serono. B. Besse: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Onxeo; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Inivata; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Biogen; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Ignyta; Research grant / Funding (institution): Ipsen; Research grant / Funding (institution): Merck; Research grant / Funding (institution): MSD Oncology; Research grant / Funding (institution): Nektar; Research grant / Funding (institution): PharmaMar; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Spectrum Pharmaceuticals; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Tiziana Therapeutics. A. Bearz: Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis. S. Peters: Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca. F. Toffalorio: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. A. Abbattista: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. H. Thurm: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. G. Peltz: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. R. Wiltshire: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. A.T. Shaw: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Genentech; Honoraria (self): Foundation Medicine; Honoraria (self): Guardant Health; Advisory / Consultancy: Roche; Advisory / Consultancy, Research grant / Funding (institution): ARIAD Pharmaceuticals; Advisory / Consultancy, Research grant / Funding (institution): Ignyta; Advisory / Consultancy: Blueprint Medicines; Advisory / Consultancy, Research grant / Funding (institution): Daiichi Sankyo; Advisory / Consultancy: EMD Serono; Advisory / Consultancy: Taiho Pharmaceutical; Advisory / Consultancy: KSQ Therapeutics; Advisory / Consultancy: Natera; Advisory / Consultancy: Loxo Pharmaceuticals; Advisory / Consultancy: Takeda; Advisory / Consultancy: Bayer; Advisory / Consultancy: Chugai Pharma; Research grant / Funding (institution): TP Therapeutics.

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Poster Discussion – NSCLC, metastatic Poster Discussion session

Invited Discussant 1484PD, 1485PD, 1486PD and 1487PD (ID 6911)

Lecture Time
16:55 - 17:10
Speakers
  • Fiona H. Blackhall (Manchester, United Kingdom)
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
16:30 - 17:45
Poster Discussion – NSCLC, metastatic Poster Discussion session

Q&A led by Discussant (ID 6914)

Lecture Time
17:10 - 17:20
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
16:30 - 17:45
Poster Discussion – NSCLC, metastatic Poster Discussion session

1488PD - Entrectinib in locally advanced/metastatic ROS1 and NTRK fusion-positive non-small cell lung cancer (NSCLC): Updated integrated analysis of STARTRK-2, STARTRK-1 and ALKA-372-001 (ID 4178)

Presentation Number
1488PD
Lecture Time
17:20 - 17:20
Speakers
  • Filippo Guglielmo Maria M. De Braud (Milan, Italy)
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
16:30 - 17:45

Abstract

Background

Entrectinib is a systemic and central nervous system (CNS)-active potent inhibitor of ROS1 and TRKA/B/C. Primary data showed that entrectinib was tolerable and achieved high objective response rates (ORR) in patients (pts) with ROS1-positive (ROS1+), ROS1 inhibitor-naïve NSCLC, and in pts with NTRK fusion-positive (NTRK+) NSCLC, including pts with baseline CNS disease. We present data from an additional 5 months of follow-up.

Methods

Pts with locally advanced/metastatic ROS1+ or NTRK+ tumours (with or without baseline CNS disease) confirmed by nucleic acid-based methods, enrolled in global phase I/II entrectinib trials (ALKA-372-001 [EudraCT 2012-000148-88], STARTRK-1 [NCT02097810], STARTRK-2 [NCT02568267]) were included. Disease burden was assessed per blinded independent central review (BICR) using RECIST v1.1, after cycle 1 (4 wks) then every 8 wks. Primary endpoints were ORR and duration of response (DOR) by BICR. Secondary endpoints included ORR and DOR in pts with or without baseline CNS disease, and safety. Intracranial (IC) ORR and DOR were evaluated in pts with baseline CNS disease.

Results

There were 53 efficacy-evaluable pts with treatment-naïve, ROS1+ NSCLC and 10 pts with NTRK+ NSCLC. As of 30 Oct 2018 (additional 5 months’ follow-up), BICR ORR: ROS1+ 79.2% (95% CI 65.9–89.2) and NTRK+ 70.0% (95% CI 34.75–93.33) with complete responses in 5 (9.4%) pts and 1 (10.0%) pt, respectively. In ROS1+ NSCLC, median DOR: 24.6 mo (95% CI 12.6–34.8); in pts with and without baseline CNS disease, ORR was 73.9% (95% CI 51.6–89.8) and 83.3% (95% CI 65.3–94.4); IC ORR was 55.0% (95% CI 31.5–76.9); and median IC DOR was 12.9 mo (95% CI 5.6–not estimable). Additional efficacy for NTRK+ NSCLC pts will be presented. Entrectinib was well tolerated with a safety profile consistent with that previously reported; there were no new or unexpected safety findings.

Conclusions

In line with the primary data, in pts with ROS1+ and NTRK+ NSCLC after an additional 5 months of follow-up, entrectinib was well tolerated and showed clinically meaningful, durable systemic and intracranial responses.

Clinical trial identification

ALKA-372-001 [EudraCT 2012-000148-88] STARTRK-1 [NCT02097810] STARTRK-2 [NCT02568267].

Editorial acknowledgement

Laura Vergoz and Charlotte Kennerley, PhD of Gardiner-Caldwell Communications; funded by F. Hoffmann-La Roche.

Legal entity responsible for the study

F. Hoffmanm-La Roche.

Funding

F. Hoffmann-La Roche.

Disclosure

F.G.M. De Braud: Advisory / Consultancy, Officer / Board of Directors: TizianaLife Sciences, BMS, Celgene, Novartis, Servier, Pharm Research Associated, Daiichi Sankyo, Ignyta, Amgen, Pfizer, Octimet Oncology, Incyte, Teofarma, Pierre Fabre, Roche, EMD Serono ; Honoraria (self), Speaker Bureau / Expert testimony, Speaker honoraria: BMS, Eli Lilly, Roche, Amgen, AstraZeneca, Gentili, Fondazione Menarini, Novartis, MSD, Ignyta, Bayer, Noema S.r.l., ACCMED, Dephaforum S.r.l., Nadirex, Roche, Biotechspert Ltd, PriME Oncology, Pfizer . S. Siena: Advisory / Consultancy: Amgen, Bayer, BMS, CheckmAb, Celgene, Daiichi-Sankyo, Incyte, Merck, Novartis, Roche-Genentech, Seattle Genetics. F. Barlesi: Research grant / Funding (institution), Institutional financial interests: AbbVie, ACEA, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer–Ingelheim, Eisai, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Genentech, Ipsen, Ignyta, Innate Pharma, Loxo, Novartis, MedImmune, Merck, MSD, Pierre Fabre, Pfizer, Sanofi-Aventis; Honoraria (self), Personal financial interests: AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer–Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer, Takeda; Non-remunerated activity/ies: Principal Investigator for AstraZeneca, BMS, Merck, Pierre Fabre and Roche sponsored trials (or ISR). A. Drilon: Honoraria (self), Advisory / Consultancy: Ignyta/Genentech/Roche, Loxo/Bayer/Lilly, Takeda/Ariad/Millenium, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Helsinn, Beigene, BergenBio, Hengrui Therapeutics, Exelixis, Tyra Biosciences, Verastem, MORE Health; Research grant / Funding (institution): Pfizer, Exelixis, GlaxoSmithKline, Teva, Taiho, PharmaMar; Research grant / Funding (self): Foundation Medicine; Licensing / Royalties: Wolters Kluwer; Non-remunerated activity/ies, Food/Beverages: Merck, Puma ; Honoraria (self), CME honoraria: Medscape, OncLive, PeerVoice, Physicians Education Resources, Targeted Oncology, Research to Practice. B.P. Simmons: Shareholder / Stockholder / Stock options: Roche (Genentech). X. Huang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech. C. Ye: Full / Part-time employment: Genentech. R.C. Doebele: Advisory / Consultancy: Pfizer, Trovagene, Ariad, Takeda, AstraZeneca, Genentech/Roche, Ignyta, Loxo, Rain; Advisory / Consultancy, Shareholder / Stockholder / Stock options, Chair of Scientific Advisory Board : Rain Therapeutics; Research grant / Funding (self), Research grant / Funding (institution): Ignyta, Loxo, Mirati; Licensing / Royalties: Abbott Molecular, Rain Therapeutics, GVKbio, Chugai, Loxo, Ignyta, Genentech, Ariad, Foundation Medicine, Black Diamond; Honoraria (self): Guardant.

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Poster Discussion – NSCLC, metastatic Poster Discussion session

1489PD - Secondary ROS1 mutations and lorlatinib sensitivity in crizotinib-refractory ROS1 positive NSCLC: Results of the prospective PFROST trial (ID 4899)

Presentation Number
1489PD
Lecture Time
17:20 - 17:20
Speakers
  • Lorenza Landi (Ravenna, Italy)
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
16:30 - 17:45

Abstract

Background

Lorlatinib, an ALK/ROS1 inhibitor, showed activity in ROS1+ NSCLC pretreated with crizotinib. However, molecular events predictive for tumor response during lorlatinib treatment are largely unknown.

Methods

The PFROST trial included ROS1+ NSCLCs refractory to crizotinib. Eligible patients received lorlatinib 100 mg daily until disease progression. Primary end point was response rate (RR). For all patients, pre-lorlatinib tumor tissue or blood sample collection was mandatory. At lorlatinib failure liquid biopsy was recommended. The samples were then run with the NEOliquid assay, specifically designed for liquid biopsies, or NEOselect, a panel optimized for formalin-fixed paraffin-embedded (FFPE) tumor tissue, covering 39 cancer related genes.

Results

From June 2017 to April 2019, 22 ROS1+ crizotinib refractory lung adenocarcinoma patients were included in 10 Institutions. Median age was 56 years (range 39-82); male/female: 8/14; ECOG PS 0 (N = 8; 36.4%), PS1 (N = 14; 63,6%); The majority had brain metastases at baseline (N = 15; 68.1%), were never smokers (N = 13; 59.1%) and received lorlatinib as third-line therapy (N = 16; 72.7%). In all cases crizotinib was the last therapy before lorlatinib. Accrual is completed and 13 patients are still receiving therapy. A total of 18 patients were evaluable for response and 7 had confirmed complete (N = 1) or partial (N = 6) responses for an overall RR of 38.8%. In 4 patients, response to therapy was not yet evaluated. A total of 10 tissue biopsies and 20 blood samples obtained after crizotinib and before lorlatinib therapy were collected. For 7 samples analyses are ongoing. Among responders, no patient harbored a secondary ROS1 mutation. Conversely, no response was observed among patients with secondary ROS1 mutations (N = 1 ROS1S1861I, N = 1 ROS1 V2054A, N = 3 ROS1G2032R). All patients harboring the ROS1G2032R mutation rapidly progressed and maintained this aberration in liquid biopsy at the time of of lorlatinib failure.

Conclusions

In our study lorlatinib confirmed its efficacy in crizotinib resistant ROS1+ NSCLC. Molecular profile of refractory patients suggests reduced efficacy in individuals harbouring crizotinib-induced secondary ROS1 mutations.

Clinical trial identification

EudraCT Number: 2016-001259-34.

Legal entity responsible for the study

Fondazione Ricerca Traslazionale.

Funding

Has not received any funding.

Disclosure

L. Landi: Advisory / Consultancy: Pzifer; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Boehringer Ingelheim. M. Tiseo: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Otsuka; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pierre Fabre. D.L. Cortinovis: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen. A. Delmonte: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Boehringer Ingelheim. D. Galetta: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim. R. Chiari: Advisory / Consultancy: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim; Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: Novartis. L. Crinò: Advisory / Consultancy: AbbVie; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Bristol; Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca. F. Cappuzzo: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim. All other authors have declared no conflicts of interest.

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Poster Discussion – NSCLC, metastatic Poster Discussion session

1490PD - A phase Ia/IIa trial of Sym015, a MET antibody mixture, in patients with advanced solid tumours (ID 1857)

Presentation Number
1490PD
Lecture Time
17:20 - 17:20
Speakers
  • D. Ross Camidge (Aurora, CO, United States of America)
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
16:30 - 17:45

Abstract

Background

MET gene amplification/mutation is implicated in oncogenesis of many tumor types. Sym015 is a recombinant antibody (Ab) mixture containing 2 humanized Abs binding non-overlapping epitopes on MET which has superior preclinical activity compared to other MET Abs. Here we present interim results from the First in Human study of Sym015.

Methods

In part 1 dose escalation, Sym015 was evaluated on every 2-week (q2w) schedule at 6/12/18/24 mg/kg doses in late line advanced solid tumor patients (pts). Based on PK/PD assessment, 18 mg/kg loading dose followed by 12 mg/kg q2w was selected as RP2D. The on-going Part 2 Dose expansion enrolls pts with MET amplification (METAmp >5 MET copies by Next Generation Sequencing (NGS) or FISH MET/CEP7 ratio >2.2 updated to ≥ 3.0) and/or MET exon 14 deletion (METEx14Δ) positive tumors. Central FISH confirmation of tumor MET status and longitudinal circulating tumor (ct)DNA profiling is performed.

Results

By April 2019, 51 pts (median age 61 yrs) have been treated, 12 pts in Part 1 and 39 pts in Part 2, the majority are non small cell lung cancer (NSCLC; 14 pts; 6 METAmp,7 METEx14Δ, 1 both) and gastric cancer (GC; 12 METAmp pts). Treatment-related adverse events (TRAE) occurred overall in 41,2%; TRAE ≥ gr3 in 9,8% (edema, colitis, septic shock, hypoalbuminemia, hypophosphatemia, increased amylase). No pts discontinued or died due to TRAE. The most common TRAE of ≥ 5% were fatigue 15.7%, peripheral edema 7,8%, nausea, decreased appetite, pruritus and abdominal pain reported by 5.9% of pts each. The table shows preliminary efficacy in NSCLC patients. Sym015 PK was slightly non-linear, with a dose-dependent t½ of 7-10 days for the first dose. 83% METAmp concordance (10/12 samples) between tumor and blood was observed.

1490PD

NSCLC PtMET Status (Local Assessment)Best Response (Best % Change From Baseline)Previous MET TKI therapyDuration of Response (weeks)
1METAmp NGS 6.8 CopiesPR (-53%)No80
2METAmp NGS >5 CopiesSD (-29%)No9, Ongoing
3METAmp NGS >5 CopiesSD (+3%)No9, Ongoing
4METEx14ΔSD (-28%)No7, Ongoing
5METAmp FISH MET/ CEP7:4.9SD (+6%)No11
6METEx14ΔSD (-4%)Yes8
7METEx14ΔSD (-21%)Yes15
8METEx14ΔSD (-20%)Yes8
9METAmp SISH MET/ CEP7: 15.2PendingNoOngoing
10METEx14ΔPendingYesOngoing
11METEx14Δ + METAmpPendingPendingOngoing
12METEx14ΔPendingNoOngoing
13METEx14ΔPendingNoOngoing
14METEx14ΔNot EvaluableYesNot Evaluable

Conclusions

Sym015 was well tolerated with early evidence of antitumor activity. Predictive biomarker analysis is underway. The study continues to enroll NSCLC patients with METAmp and/or METEx14Δ. MET screening in blood seems feasible and may be included in future trials.

Clinical trial identification

NCT02648724.

Legal entity responsible for the study

Symphogen A/S.

Funding

Symphogen A/S.

Disclosure

D.R. Camidge: Advisory / Consultancy: 2019: Takeda, CBT Pharmaceuticals, Daiichi-Sankyo (ILD adjudication committee), G1 Therapeutics (DSMB), Bio-Thera (DSMB), Blueprint; Advisory / Consultancy: 2018: AstraZeneca, Takeda, Arrys/Kyn, Regeneron, Hengrui, G1 Therapeutics (DSMB), Daiichi Sankyo (ILD adjudication committee), Hansoh (SRC), Bio-Thera (DSMB), Ribon, BMS, Blueprint, Roche/Genentech, Inivata; Advisory / Consultancy: 2017: Genoptix, G1 Therapeutics (DSMB), Mersana Therapeutics, Roche/Genentech, Takeda, Ignyta, Daiichi Sankyo (ILD adjudication committee), Hansoh SRC, Bio-Thera DSMB, Lycera, Revolution Med; Research grant / Funding (self), Research grant / Funding (institution): 2017: Takeda Investigator-initiated Trial; Research grant / Funding (self), Research grant / Funding (institution), Company Sponsored Trials at Institution: 2018/9: AbbVie, AstraZeneca, BMS, Hansoh, Lycera, MedImmune, Merck, Pfizer, Phosplatin, Roche/Genentech, Seattle Genetics, Symphogen, Takeda. F. Janku: Research grant / Funding (self): Novartis, Genentech, BioMed Valley Discoveries, Astellas, Agios, Plexxikon, Deciphera, Piqur, Symphogen, Bristol-Myers Squibb, Asana, Upsher-Smith Laboratories; Advisory / Consultancy: Guardant Health, IFM Therapeutics, Synlogic, Deciphera; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Trovagene; Advisory / Consultancy: Immunomet. D.V. Catenacci: Honoraria (self), Advisory / Consultancy: Merck, BMS, Lilly, Astellas, Gritstone, Taiho, Five Prime, Genentech Roche, Foundation Medicine, Guardant Health, Tempus. H.C. Chung: Honoraria (self): Merck-Serono, Lilly, Foundation Medicine; Advisory / Consultancy: Taiho, Celltrion, MSD, Lilly,Quintiles, BMS, Merck-Serono; Research grant / Funding (institution): Lilly, GSK, MSD, Merck-Serono, BMS-ONO, Taiho. A. Dowlati: Advisory / Consultancy: Seattle genetics, Takeda, AbbVie; Research grant / Funding (institution): Takeda, Taiho, Roche, EMD Serono, Bayer, Tesaro, Regeneron, Amgen, Mirati, BMS. K.S. Rohrberg: Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): Loxo Oncology, Orion Pharma, Pfizer, PUMA, Cantargia, Genmab, Novartis, Incyte, Bayer, AstraZeneca, Alligator, Merck, BMS; Travel / Accommodation / Expenses: Sanofi; Research grant / Funding (institution): Symphogen. T.T. Poulsen: Full / Part-time employment: Symphogen A/S. H. Rudbæk: Full / Part-time employment: Symphogen A/S. L. Alifrangis: Full / Part-time employment: Symphogen A/S. R.P. Dalal: Full / Part-time employment: Symphogen A/S. All other authors have declared no conflicts of interest.

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Poster Discussion – NSCLC, metastatic Poster Discussion session

LBA85 - Longitudinal circulating tumour DNA (ctDNA) monitoring for early detection of disease progression and resistance in advanced NSCLC in FLAURA (ID 2685)

Presentation Number
LBA85
Lecture Time
17:20 - 17:20
Speakers
  • Jhanelle E. Gray (Tampa, United States of America)
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
16:30 - 17:45

Abstract

Background

In the phase III FLAURA study (NCT02296125), the 3rd-generation EGFR-TKI osimertinib showed superior efficacy to comparator EGFR-TKIs in previously untreated EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC). Here we report results from an exploratory analysis of ctDNA for the early detection of disease progression (PD) in FLAURA.

Methods

Treatment-naïve patients (pts) with EGFRm (ex19del/L858R) locally advanced/metastatic NSCLC (n = 556) were randomised 1:1 (osimertinib 80 mg qd: comparator [gefitinib 250 mg qd/erlotinib 150 mg qd]). Plasma samples were collected on Days 1, 8 and 15, then every 21 days for weeks (W) 3–18, then every 6W thereafter. In pts who had a plasma sample on PD and/or discontinuation, ctDNA droplet digital PCR (ddPCR; Biodesix) for EGFRm (ex19del/L858R/T790M) was performed at all available time points and C797S for post-W6 time points. C797S and T790M were the only resistance mutations assayed. ctDNA progression was defined with respect to the nadir ctDNA result and its proximity to the ddPCR detection and quantification limits.

Results

The ctDNA progression analysis included 122/556 (22%) pts with valid longitudinal monitoring ddPCR data and RECIST PD by DCO1 (12 June 2017). Across both arms, ctDNA progression preceded or co-occurred with PD in 80/122 (66%) pts with 2.7 months (mo) median lead time; 9.5 mo median progression-free survival (mPFS; n = 80). Acquired C797S or T790M was detected in 57/122 (47%) pts with ctDNA progression (osimertinib 4/50 [8%] C797S, comparator 53/72 [74%] T790M); median time to detection was 16.7 and 8.4 mo for the osimertinib and comparator arms, respectively, mirroring overall mPFS. In pts with ctDNA progression and PD (n = 106), acquired T790M and C797S were detected either at the same time as, or earlier than PD in 41/106 (38%) pts (osimertinib 2/39 [5%], comparator 39/67 [58%]); median lead time was 1.4 mo.

Conclusions

ctDNA monitoring may allow for earlier identification of pts who progress on first-line EGFR-TKI therapy and the detection of EGFR-mediated resistance mechanisms in advance of PD in EGFRm NSCLC. Future work aims to explore early detection of non-EGFR-mediated resistance.

Clinical trial identification

NCT02296125.

Editorial acknowledgement

Writing support was provided by Donna Tillotson, PhD of iMed Comms, Macclesfield, UK, an Ashfield Company, part of UDG Healthcare plc, and funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

J.E. Gray: Research grant / Funding (institution): Array; Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Takeda. N. Peled: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Takeda; Advisory / Consultancy: Eli Lilly; Honoraria (self): Foundation Medicine; Shareholder / Stockholder / Stock options: NovellusDx; Honoraria (self): Gaurdant360. A. Markovets: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. N. Nogami: Honoraria (self): Pfizer Inc.; Honoraria (self): Chugai Pharmaceutical Co. Ltd; Honoraria (self): Eli Lilly; Honoraria (self): Taiho Pharmaceutical Co. Ltd; Honoraria (self): AstraZeneca; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self): Ono Pharmaceutical Co. Ltd; Honoraria (self): BMS; Honoraria (self): MSD. B.C. Cho: Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Bayer; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): MOGAM Institute; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Dong-A ST; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Licensing / Royalties: Champions Oncology; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Janssen; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Yuhan; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Ono; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Dizal Pharma; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): MSD; Honoraria (institution), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy: BMS; Honoraria (institution), Advisory / Consultancy: Pfizer; Honoraria (institution), Advisory / Consultancy: Eli Lilly; Honoraria (institution), Advisory / Consultancy: Takeda; Shareholder / Stockholder / Stock options: TheraCanVac Inc. B. Chewaskulyong: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca. M. Majem: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer; Advisory / Consultancy: Tesaro; Speaker Bureau / Expert testimony: Hellsin; Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pierre Fabre; Speaker Bureau / Expert testimony: Amgen. K. Vishwanathan: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. A. Todd: Full / Part-time employment: AstraZeneca. Y. Rukazenkov: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. M. Johnson: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. C. Barrett: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. J. Chmielecki: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. R. Hartmaier: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca; Shareholder / Stockholder / Stock options, Licensing / Royalties, Nfe2l2 exon 2 ano/or exon 3 loss from work conducted at Foundation Medicine; provisional patent filed: Foundation Medicine. S.S. Ramalingam: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy: Roche/Genentech; Honoraria (self), Advisory / Consultancy: Loxo; Honoraria (self), Advisory / Consultancy: Nektar; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): Advaxis; Research grant / Funding (institution): Takeda. All other authors have declared no conflicts of interest.

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Poster Discussion – NSCLC, metastatic Poster Discussion session

Invited Discussant 1488PD, 1489PD, 1490PD and LBA85 (ID 6912)

Lecture Time
17:20 - 17:35
Speakers
  • Ross Soo (Singapore, Singapore)
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
16:30 - 17:45
Poster Discussion – NSCLC, metastatic Poster Discussion session

Q&A led by Discussant (ID 6913)

Lecture Time
17:35 - 17:45
Location
Cordoba Auditorium (Hall 7), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
16:30 - 17:45