ESMO Supporter 2018

Displaying One Session

ICM - Room 14b Poster Discussion session
Date
19.10.2018
Time
14:00 - 15:00
Location
ICM - Room 14b
Chairs
  • Raffaele Califano (Manchester, GB)
  • Pasi A. Janne (Boston, US)
  • Fedor Moiseyenko (St.-Petersburg, RU)
Poster Discussion session - NSCLC, metastatic 1 Poster Discussion session

LBA57 - Overall survival results of ceritinib in ALKi-naïve patients with ALK-rearranged NSCLC (ASCEND-3)

Presentation Number
LBA57
Lecture Time
14:00 - 14:00
Speakers
  • Enriqueta Felip (Barcelona, ES)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:00

Abstract

Background

The previous analysis of phase 2, ASCEND-3 study (NCT01685138; data cutoff: November 15, 2015) demonstrated prolonged median progression-free survival (mPFS) with ceritinib 750 mg/d (fasted) in ALKi-naïve patients with ALK+ NSCLC, who had received ≤3 prior lines of chemotherapy. The current analysis (data cutoff: January 22, 2018) from ASCEND-3 study reports the final safety and efficacy results including overall survival (OS).

Methods

ASCEND-3 is a multicenter, single-arm, open-label, phase 2 study in ALKi-naïve patients (aged, ≥18 years) with locally advanced or metastatic ALK+ NSCLC, who had received ≤3 lines of chemotherapy. Patients received oral ceritinib 750 mg/d (fasted). Primary endpoint was overall response rate (ORR) per RECIST v1.1 (by investigator). Secondary endpoints were ORR (by blinded independent review committee [BIRC]); overall intracranial response rate (OIRR), duration of response (DOR), disease control rate (DCR), PFS (by investigator and BIRC); OS; and safety.

Results

Of 124 ceritinib-treated patients, 123 (99.2%) had received prior antineoplastic regimens (31 patients [25.0%], ≥3 regimens), and 49 (39.5%) had baseline brain metastases. Median follow-up time was 52.14 months (range, 48.4-60.1). Median duration of drug exposure was 23.2 months (range, 0.1-55.2). Median OS was 51.3 months (95% CI: 42.7, 55.3). Other efficacy results are shown in the table below. The most common adverse events (AEs [all grades], ≥60% of patients), suspected to be drug related, were diarrhea (83.1%), nausea (76.6%), and vomiting (69.4%). Grade 3/4 AEs suspected to be drug related were reported in 81 patients (65.3%). Overall, 18 patients (14.5%) had an AE leading to treatment discontinuation.

Investigator Assessment

(N* = 124)

BIRC Assessment

(N* = 124)
Overall response rate, n (%) (95% CI) 84 (67.7) (58.8, 75.9) 79 (63.7) (54.6, 72.2)
Disease control rate, n (%) (95% CI) 112 (90.3) (83.7, 94.9) 107 (86.3) (79.0, 91.8)

Median duration of response (in responders), months (95% CI)

M = 84

24.0 (14.8, 37.5)

M = 79

27.3 (16.6, 44.3)
Median progression-free survival, months (95% CI) 16.6 (11.0, 23.2) 19.4 (10.9, 29.3)

*Total number of patients included in the full analysis set.

Total number of patients with confirmed complete response or partial response.

Conclusions

Ceritinib demonstrated prolonged and clinically meaningful OS, PFS, and DOR in chemotherapy pretreated (≤3 lines), ALKi-naïve patients with ALK+ NSCLC. The safety profile is consistent with the previous studies.

Clinical trial identification

NCT01685138

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Poster Discussion session - NSCLC, metastatic 1 Poster Discussion session

LBA58 - Intracranial efficacy of brigatinib (BRG) vs crizotinib (CRZ) in the phase 3 ALTA-1L trial

Presentation Number
LBA58
Lecture Time
14:00 - 14:00
Speakers
  • Sanjay Popat (London, GB)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:00

Abstract

Background

BRG, a next-generation ALK inhibitor, has robust efficacy in CRZ-resistant ALK+ NSCLC. ALTA-1L evaluated the efficacy of BRG vs CRZ in TKI-naive ALK+ NSCLC patients (pts). The primary endpoint of blinded independent review committee (BIRC)-assessed PFS was met at first interim analysis (IA) and previously reported (HR, 0.49; P=0.0007). Here we report detailed intracranial efficacy from the first IA of ALTA-1L (NCT02737501).

Methods

The open-label, multicenter study enrolled pts with ALK inhibitor-naive stage IIIB/IV ALK+ NSCLC. Pts were stratified by presence of baseline (BL) brain metastases and history of chemotherapy for advanced disease and randomized 1:1 to BRG 180 mg qd with 7-day lead-in at 90 mg or CRZ 250 mg bid. Primary endpoint: BIRC–assessed PFS (RECIST v1.1). IAs were planned at ~50% and ~75% of 198 expected PFS events. Secondary endpoints included intracranial ORR (iORR) and intracranial PFS (iPFS). An exploratory competing risks analysis of intracranial progression (per CNS BIRC), systemic progression (per systemic BIRC), and death was also performed.

Results

Of 275 randomized pts (BRG/CRZ, n=137/138), 31%/34% had BL brain metastases (BIRC-assessed); 13%/14% had prior brain radiotherapy. At data cut-off (19 February 2018; median follow-up, 11/9.3 mo), iPFS in ITT population was significantly improved with BRG (HR, 0.42 [95% CI, 0.24–0.70]; P=0.0006). In the ITT population competing risks analysis, time to intracranial progression without prior systemic progression was significantly improved with BRG (HR, 0.30 [95% CI, 0.15–0.60]; P<0.001); 1-year cumulative incidence (BRG vs CRZ): 12% (95% CI, 6–20) vs 23% (95% CI, 15–31). Time to systemic progression without prior intracranial progression was also improved with BRG (HR, 0.51 [95% CI, 0.30–0.86]; P=0.017). Additional intracranial efficacy results are presented in the Table.

Conclusions

BRG has superior intracranial activity vs CRZ in ALK TKI-naive pts with ALK+ NSCLC.

BIRC-Assessed Endpoint BRG CRZ P Value

All patients (ITT), n

137 138
iPFS events, n (%) 22 (16) 39 (28)
Median iPFS, mo NR (NRa) NR (11–NRa)
1-y iPFS, % 78 (68–85a) 61 (50–71a)
iPFS hazard ratio (95% CI) 0.42 (0.24–0.70a) 0.0006b
Any baseline brain metastases, n 43 47
iPFS events, n (%) 11 (26) 28 (60)
Median iPFS, mo NR (11–NRa) 6 (4–9a)
1-y iPFS, % 67 (47–80a) 21 (6–42a)
iPFS hazard ratio (95% CI) 0.27 (0.13–0.54a) <0.0001b
iORRc, % 79 (64–90a) 23 (12–38a) <0.0001d
Confirmed iORR, % 67 (51–81a) 17 (8–31a) <0.0001d
Measurable brain metastases, n 18 21
iORRc, % 83 (59–96a) 33 (15–57a) 0.0023d
Confirmed iORR, % 78 (52–94a) 29 (11–52a) 0.0028d

NR, not reached

a95% CI; bLog-rank; cResponse, ≥1 assessment; dCochran-Mantel-Haenszel test

Clinical trial identification

NCT02737501; March 30, 2016

Editorial Acknowledgement

Professional medical writing assistance was provided by Lauren Gallagher, PhD, of Peloton Advantage, LLC, Parsippany, New Jersey, USA, and funded by Millennium Pharmaceuticals, Inc.

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Poster Discussion session - NSCLC, metastatic 1 Poster Discussion session

1379PD - Impact of the EML4-ALK variant on the efficacy of alectinib (ALC) in untreated ALK+ advanced NSCLC (aNSCLC) in the global phase III ALEX study

Presentation Number
1379PD
Lecture Time
14:00 - 14:00
Speakers
  • Rafal Dziadziuszko (Gdansk, PL)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:00

Abstract

Background

The ALEX study (NCT02075840) showed superior investigator (INV)-assessed PFS with ALC vs crizotinib (CZ) (stratified HR 0.47, 95% CI 0.34–0.65, p < 0.001): median PFS not estimable ALC vs 11.1 months [m] CZ. Follow-up analysis (cut-off Dec 1 2017) indicated a median PFS of 34.8m ALC vs 10.9m CZ (stratified HR 0.43, 95% CI 0.32–0.58) [Camidge et al. ASCO 2018]. We report efficacy data from ALEX by EML4-ALK variant group.

Methods

Patients (pts) with stage IIIB/IV ALK+ NSCLC (by central IHC) and no prior systemic therapy for aNSCLC were enrolled (asymptomatic CNS metastases allowed) and randomized 1:1 to receive ALC 600mg BID (n = 152) or CZ 250mg BID (n = 151). ALK rearrangement was assessed in baseline samples by next generation sequencing (NGS; FoundationOne® [tissue] and Foundation ACT [plasma]) using the primary data cut-off (Feb 9 2017). PFS (INV-assessed, RECIST v1.1), objective response rate (ORR) and duration of response (DoR) were assessed by EML4-ALK variant.

Results

Baseline demographics/PFS were comparable between the biomarker evaluable populations (BEP; n = 203 tissue, n = 222 plasma) and the ITT population (n = 303). ALK rearrangement was detected by NGS in 136/203 (67%; tissue) and 145/222 (65%; plasma) pts. EML4-ALK variants 1, 2 and 3a/b accounted for ∼90% of variants (variant 2 was least prevalent). In the primary data set analysis, no significant difference was observed in INV-assessed PFS or ORR between the EML4-ALK variant groups in both tissue and plasma BEPs for ALC- and CZ-treated pts (Table). Median DoR was similar for EML4-ALK variants 1, 2 and 3 in the ALC arm but not in the CZ arm. Efficacy data by independent review were comparable.

Conclusions

These exploratory post-hoc analyses from the ALEX study show that the greater efficacy benefit of ALC vs CZ in ALK+ aNSCLC appeared independent of the EML4-ALK variant.

Clinical trial identification

NCT02075840.

Legal entity responsible for the study

F. Hoffmann-La Roche.

Funding

F. Hoffmann-La Roche.

Disclosure

R. Dziadziuszko: Advisory board or board of directors: Roche, AstraZeneca, Pfizer, Bristol-Myers Squibb, Ignyta; Corporate-sponsored research: Roche, Pfizer, Novartis, Ignyta. T.S. Mok: Stock ownership: Sanomics Ltd.; Advisory board: AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, BI, Clovis Oncology, Merck Serono, MSD, Novartis, SFJ Pharmaceutical, Acea Biosciences, Inc., Vertex Pharmaceuticals, BMS, geneDecode Co., Ltd., OncoGenex Technologies Inc., Celgene, Ignyta, Inc., Cirina, Fishawack Facilitate Ltd., Janssen, Takeda, ChiMed; Board of directors: IASLC, ASCO, ChiMed, Chinese Lung Cancer Research Foundation Ltd., Chinese Society of Clinical Oncology (CSCO), Hong Kong Cancer Therapy Society (HKCTS); Corporate-sponsored research: AstraZeneca, BMS, Clovis Oncology, MSD, Novartis, Pfizer, Roche, SFJ, XCovery. D.R. Camidge: Steering committee for trial, compensated ad hoc advising to self: Roche. A.T. Shaw: Consulting or advisory board: Genentech/Roche, Novartis, Pfizer, Ariad/Takeda, Ignyta, Daiichi-Sankyo, EMD Serono, Taiho, Blueprint Medicine, Loxo, Natera, Foundation medicine, TP Therapeutics. J. Noe: Employee: Hoffmann La Roche. M. Nowicka: Employed as a contractor: Roche. T. Liu: Stock ownership and employee: Roche. S. Peters: Advisory board/ board of directors. All other authors have declared no conflicts of interest.

ALC
CZ
Tissue BEP
Plasma BEP
Tissue BEP
Plasma BEP
V1V2V3V1V2V3V1V2V3V1V2V3
Median PFS, mn = 25n = 8n = 21n = 22n = 10n = 25n = 28n = 5n = 25n = 28n = 12n = 24
NE11.5NENE14.9NE12.98.814.87.48.89.1
P = 0.0924P = 0.3777P = 0.8584P = 0.8317
ORR, %n = 22n = 8n = 21n = 21n = 10n = 24n = 27n = 5n = 25n = 27n = 11n = 24
91.062.566.790.570.083.370.4100.064.063.063.645.8
P = 0.1034§P = 0.3538§P = 0.2751§P = 0.4071§
Median DoR, mn = 20n = 5n = 14n = 19n = 7n = 20n = 19n = 5n = 16n = 17n = 7n = 11
18.416.618.416.916.817.611.17.212.05.67.211.1

V=variant; NE=not estimable; BEP=biomarker evaluable population

Log-rank test comparing all 3 variants;

Pearson's chi-squared test comparing all 3 variants

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Poster Discussion session - NSCLC, metastatic 1 Poster Discussion session

1380PD - Efficacy of lorlatinib in patients (pts) with ROS1-positive advanced non-small cell lung cancer (NSCLC) and ROS1 kinase domain mutations

Presentation Number
1380PD
Lecture Time
14:00 - 14:00
Speakers
  • Benjamin J. Solomon (Melbourne, AU)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:00

Abstract

Background

Lorlatinib is a potent, brain-penetrant, 3rd-generation ALK/ROS1 TKI active against most known resistance mutations (mut). In a Ph I/II study, lorlatinib showed robust clinical activity in ALK+ or ROS1+ NSCLC pts, most of whom had CNS metastases and were heavily pre-treated. Efficacy and molecular profiling based on tumor tissue were explored based on prior TKI treatment.

Methods

Pts with ROS1+ NSCLC (N = 59) were enrolled from the ongoing Ph I/II study (NCT01970865); samples were collected for molecular profiling. DNA was extracted from tumor tissues (archival or de novo samples) and analyzed with a ROS1 mut-focused next generation sequencing (NGS) panel (Molecular MD, Portland, OR, USA).

Results

Based on the tumor tissue analysis set, 51 tumor samples (13 were ROS1 TKI-naïve [7 had de novo tissue evaluated in this analysis, 6 had archival tissue]; 38 were TKI-pre-exposed [21 de novo, 17 archival]) were collected from Ph I/II ROS1+ pts; 35 (68.6%) had no detectable ROS1 mut while 7 (13.7%) harbored ≥1 ROS1 mut; 9 (17.6%) samples were not analyzable. Four unique ROS1 mut were detected, with G2032R being the most frequent (57.1%). Among 13 ROS1 TKI-naïve pts, none had a detectable ROS1 mut; objective response rate (ORR) was 76.9%. In pts previously treated with crizotinib ± chemotherapy, 21 out of 34 (61.8%) had no ROS1 mut detected, 6 (17.6%) harbored a mut and 7 were not analyzable. Overall ORR was 29.4%, 23.8% for pts with no detectable ROS1 mut and 33.3% for pts with a mut. Finally, in 4 pts (all with de novo samples) treated with 1 non-crizotinib TKI or ≥ 2 TKIs (which could include crizotinib), only 1 (25%) harbored a ROS1 mut and no responses were observed. Of 4 pts with the G2032R mut, all had stable disease (SD) (duration 2.0 to 9.6 months); 3 pts with other ROS1 mut had a partial response (DOR 11.1 and 14.9+ months [+ denotes pts still on study with ongoing responses]) or SD. Plasma DNA analysis will be reported.

Conclusions

Lorlatinib evoked responses in treatment-naive pts or those resistant to prior ROS1 TKIs. Lorlatinib also exhibited activity against some ROS resistance mut, and provided some disease control for tumors harboring the difficult-to-treat G2032R mut with BOR of SD.

Legal entity responsible for the study

Pfizer, Inc.

Funding

Pfizer.

Editorial Acknowledgement

Editorial support was provided by Jade Drummond and Brian Szente of inScience Communications, Springer Healthcare (Chester, UK and Philadelphia, PA, US), and was funded by Pfizer.

Disclosure

B.J. Solomon: Honoraria: Bristol-Myers Squibb, AstraZeneca; Royalty, IP Rights/Patent Holder: Veristrat (Biodesix); Travel, accommodations, expenses: AstraZeneca, Roche, Merck, Bristol-Myers Squibb, Novartis; Institutional: Speakers or advisory board: AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche/Genentech, Novartis; Research funding: Pfizer. J.-F. Martini: Employee and Stock: Pfizer. S-H.I. Ou: Consulting or advisory role: Pfizer, Roche/Genentech, Novartis, AstraZeneca, Takeda, Foundation Medicine; Speakers' bureau: Genentech, AstraZeneca, Takeda; Honoraria: Pfizer, Roche Pharma AG, Genentech/Roche, Ariad/Takeda, Novartis, AstraZeneca, Foundation Medicine; Institutional, Research funding: Pfizer, Roche Pharma AG, AstraZeneca/MedImmune, AstraZeneca, Clovis Oncology, Ariad, Ignyta, Peregrine Pharmaceuticals, GlaxoSmithKline, Astellas Pharma, Chugai Pharma. R.A. Soo: Consulting or advisory role: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Merck Sharp & Dohme, Novartis, Pfizer, Roche/Genentech, Taiho Pharmaceutical; Honoraria: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche/Genentech; Research funding: AstraZeneca. A. Bearz: Speakers’ Bureau: MSD, Roche, BMS, Pfizer, Takeda, Eli-Lilly, Novartis; Consultant: MSD, Roche, BMS, Pfizer, Takeda, Eli-Lilly, Novartis. S. Li: Employment: Pfizer. H. Thurm: Employment and stock: Pfizer. G.J. Riely: Consultant: Genentech; Travel, accommodations, expenses: Merck Sharp & Dohme. Institutional: Research funding: Novartis, Roche/Genentech, Millennium, GlaxoSmithKline, Pfizer, Infinity Pharmaceuticals, Ariad. T.M. Bauer: Employment: Tennessee Oncology, Sarah Cannon Research Institute; Consulting or advisory role: Ignyta, Guardant Health, Loxo, Pfizer, Moderna Therapeutics; Institutional: Research funding: Daiichi Sankyo, Medpacto, Inc., Incyte, Mirati Therapeutics, MedImmune, Abbvie, AstraZeneca, Leap Therapeutics, MabVax, Stemline Therapeutics, Merck, Lilly, GlaxoSmithKline, Novartis, Pfizer, Principa Biopharma, Genentech/Roche, Deciphera, Merrimack, Immunogen, Millennium, Ignyta, Calithera Biosciences, Kolltan Pharmaceuticals, Principa Biopharma, Peleton, Immunocore, Roche, Aileron Therapeutics, Bristol-Myers Squibb, Amgen, Moderna Therapeutics, Sanofi, Boehringer Ingelheim, Astellas Pharma. A.T. Shaw: Speaker or advisory board: Pfizer, Novartis, Genentech, Roche, Ariad, Takeda, Ignyta, Blueprint Medicines, Loxo, Daiichi Sankyo, EMD Serono, Taiho Pharmaceutical, KSQ Therapeutics, Natera; Honoraria: Pfizer, Novartis, Roche/Genentech, Foundation Medicine, Takeda; Research funding: Pfizer, Novartis, Roche/Genentech. All other authors have declared no conflicts of interest.

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Poster Discussion session - NSCLC, metastatic 1 Poster Discussion session

LBA59 - Primary efficacy and updated safety of ceritinib (450 mg or 600 mg) with food vs 750 mg fasted in ALK+ metastatic NSCLC ASCEND-8)

Presentation Number
LBA59
Lecture Time
14:00 - 14:00
Speakers
  • Byoung Chul Cho (Seoul, KR)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:00

Abstract

Background

Previous PK analysis results from ASCEND-8 study (NCT02299505) showed that ceritinib 450 mg with food had comparable exposure and more favorable GI safety profile than ceritinib 750 mg fasted in patients (pts) with ALK+ NSCLC.

Methods

In this open-label, phase 1, 3-arm study, pts with treatment-naïve or pre-treated ALK+ advanced/metastatic NSCLC were randomized 1:1:1 to ceritinib 450 or 600 mg with food and 750 mg fasted, stratified by prior treatment and presence/absence of brain metastasis at screening. Key secondary endpoints were overall response rate (ORR) and duration of response, per BIRC using RECIST 1.1. Efficacy analysis was based on all treatment-naïve pts with ALK+ defined by IHC. Safety analysis was based on all pts who received ≥1 dose of study drug. Primary efficacy analysis and updated safety results are presented here (data cut off: 27 March 2018).

Results

A total of 306 pts were randomized to ceritinib 450 mg fed (n=108) or 600 mg fed (n=87) or 750 mg fasted (n=111). Of those, 198 were treatment-naïve with ALK+ by IHC and were assessed for efficacy (450 mg fed [n=73], 600 mg fed [n=51], and 750 mg fasted [n=74]). Median duration of study follow up was 19.6 months (mo) (range, 4.2-35.3) in all randomized pts and 14.3 mo (range, 4.2-30.2) in treatment-naïve pts who were ALK+ by IHC. ORR by BIRC was 78.1% (95% CI, 66.9-86.9), 72.5% (95% CI, 58·3-84·1), and 75.7% (95% CI, 64.3-84.9) in the 450 mg fed, 600 mg fed and 750 mg fasted arms, respectively. Other efficacy results are shown in the table. The 450 mg fed arm, when compared to 600 mg fed and 750 mg fasted arms, showed highest median relative dose intensity (100% vs 78.5% vs 83.7%), lowest proportion of pts with dose reductions (24.1% vs 65.1% vs 60.9%), all grade GI toxicities (75.9% vs 82.6% vs 91.8%) and grade 3/4 GI toxicities (2.8% vs 8.1% vs 13.6%).

BIRC assessment

Ceritinib 450 mg fed

(N = 73)

Ceritinib 600 mg fed

(N = 51*)

Ceritinib 750 mg fasted

(N = 74)

Overall response rate, n (%)

(95% CI)

57 (78.1)

(66.9-86.9)

37 (72.5)

(58.3-84.1)

56 (75.7)

(64.3-84.9)

Disease control rate, n (%)

(95% CI)

66 (90.4)

(81.2-96.1)

48 (94.1)

(83.8-98.8)

67 (90.5)

(81.5-96.1)

Median duration of response (in
responders), months (95% CI)

Estimated 18-month event-free probability, % (95% CI)

M† = 57

NE (11.2-NE)

52.9 (30.9-70.8)

M† = 37

20.7 (15.8-NE)

61.1 (36.7-78.5)

M† = 56

15.4 (8.3-NE)

36.7 (14.5-59.4)

Median time to response, weeks

(95% CI)

6.3

(6.1-6.9)

6.3

(6.1-9.3)

6.3

(6.1-7.1)

Median progression-free survival, months (95% CI)

Estimated 18-month event-free probability, % (95% CI)

NE (11.8-NE)

50.8 (33.7-65.7)

17.0 (10.1-NE)

48.6 (30.7-64.3)

12.2 (8.2-NE)

40.9 (23.3-57.8)

*The 600 mg fed arm has a lower number of patients because, based on the primary pharmacokinetic analysis results, the 450 mg fed arm was considered the most favorable fed dose and enrollment to the ceritinib 600 mg dose with food was closed.

†M is the number of patients included in the duration of response analysis by BIRC analysis

BIRC, blinded independent review committee; NE, not estimable

Conclusions

Ceritinib 450 mg fed dose compared to 750 mg fasted showed consistent anti-tumor efficacy and improved GI tolerability in pts with ALK+ advanced NSCLC.

Clinical trial identification

NCT02299505

Editorial Acknowledgement

We thank Shiva Krishna Rachamadugu, Novartis Healthcare Pvt. Ltd., for providing medical editorial assistance with this abstract

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Poster Discussion session - NSCLC, metastatic 1 Poster Discussion session

Invited Discussant LBA57, LBA58, 1379PD, 1380PD and LBA59

Lecture Time
14:00 - 14:20
Speakers
  • Pasi A. Janne (Boston, US)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:00
Poster Discussion session - NSCLC, metastatic 1 Poster Discussion session

Q&A led by Discussant

Lecture Time
14:20 - 14:30
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:00
Poster Discussion session - NSCLC, metastatic 1 Poster Discussion session

LBA60 - Uncommon EGFR mutations in lung adenocarcinomas: clinical features and response to tyrosine kinase inhibitors

Presentation Number
LBA60
Lecture Time
14:30 - 14:30
Speakers
  • Aurélien Brindel (Bron, FR)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:00

Abstract

Background

The detection of pro-oncogenic mutations such as mutations in the epidermal growth factor receptor (EGFR) allowed the development of targeted therapies as inhibitor of tyrosine kinase (ITK)(1-3). Rare mutations need to be further investigated and their clinical and therapeutic significance is still unknown (4). We conducted a retrospective study to estimate the incidence and to describe the pathological characteristics of rare EGFR mutations as well as the clinical features detected among cases of lung adenocarcinomas analysed in a single molecular platform in Lyon, France.

Methods

A total of 7539 molecular analyses were performed at the regional genomics facility of the Lyon University Hospital; techniques included Sanger sequencing and next generation sequencing (from 2009 to 2017) covering exons 18 to 21 of the EGFR. EGFR-mutant tumors excluding L858R, exon 19 deletions, T790M and exon 20 insertions. Mutations were reviewed by two pathologists. The clinical data were collected from the medical records of the patients.

Results

A total of 857 EGFR somatic mutations were identified, including 95 (11%) considered as uncommon EGFR-mutations: there were 47 (50%) exon 18 mutations, including E709X (15%) and G719X (35%), 26 (27%) exon 20 mutations, including S768I (9%) and A767_V769dup (18%), and 22 (23%) L861Q in exon 21 mutations. Interestingly, 27(28%) presented another mutation of which 9 with L858R. Patients treated with first-line chemotherapy had a longer median OS than patients treated with TKI; 27.7 months 95% CI [21.6-35] vs 16.9 months 95% CI [13.6-25.9] p=0.075 all mutations included. Overall survival was correlated with the type of mutation. The mutations of exon 18 and exon 20 were correlated with a better prognosis. On the other hand, the mutation L861Q was linked with a bad prognosis. The presence of a second rare EGFR mutation was correlated with better overall survival (p = 0.002).

Conclusions

In this study, we observed a tendency for chemotherapy to improve survival compared to TKI among rare-EGFR mutation cases. Noteworthy, some mutations showed a better prognosis than others as well as the association with a double mutation in patients treated by ITK. A deeper analysis within a larger cohort would help to stratify the answer to the different treatment for each rare mutation.

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Poster Discussion session - NSCLC, metastatic 1 Poster Discussion session

1381PD - Gefitinib With or Without Pemetrexed in Nonsquamous (NS) Non–Small Cell Lung Cancer (NSCLC) With EGFR Mutation (mut): Final Overall Survival (OS) Results From a Randomized Phase II Study

Presentation Number
1381PD
Lecture Time
14:30 - 14:30
Speakers
  • James Chih-Hsin Yang (Taipei, TW)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:00

Abstract

Background

The combination of pemetrexed (P)-based chemotherapy with EGFR-tyrosine kinase inhibitors (TKI) has resulted in improved efficacy vs EGFR-TKI alone for treatment (tx) of advanced NSCLC with EGFR-mut. The objective of this disclosure is to report OS, updated progression-free survival (PFS), and safety of P+Gefitinib (G) vs G alone in patients (pts) with advanced NS NSCLC with EGFR-mut.

Methods

Primary outcome of this phase II, multicenter, randomized study has been published. Pts were randomly assigned to receive P+G or G alone at a ratio of 2:1 (P, 500 mg/m2 on day (d) 1 of every 21-d cycle; G, 250 mg/d). Primary and secondary objectives were PFS and OS, respectively. Adjusted Cox regression model was used to estimate adjusted HR for difference between tx arms.

Results

191 pts were randomized to P+G (n = 126) or G (n = 65). Majority of the pts were female (P+G [65%], G [63%]), non-smokers (P+G [64%], G [72%]), and had stage IV disease (P+G [83%], G [88%]). At final database lock, 111 (58.1%) pts had OS events (death; P+G [n = 72], G [n = 39]) while 164 pts had PFS events (progression or death; P+G [n = 102], G [n = 62]). OS was numerically higher in pts receiving P+G (43.4 months; 95% CI, 33.4-50.8) vs G alone (36.8 months; 95% CI, 26.7-42.6); adjusted HR, 0.77; 95% CI, 0.5-1.2; one-sided P = 0.105. In this updated analysis, PFS continued to be prolonged in P+G group (16.2 months; 95% CI, 12.6-18.7) vs G alone (11.07 months; 95% CI, 9.7-13.8); adjusted HR, 0.67; 95% CI, 0.5-0.9; one-sided P = 0.009. A higher % of pts in G arm received post-discontinuation systemic tx, (P+G, 68.3%; G, 78.5%), including 37 (56.9%) pts who received P. The most common drug related all grade adverse events (AEs) reported for P+G vs G were rash (53.2% vs 55.4%), diarrhea (45.2% vs 47.7%), and pruritus (35.7% vs 32.3%). Thirteen pts reported serious AEs (SAEs; P+G [n = 12, G [n = 1]); 1 pt in each arm discontinued due to SAEs. Two deaths were reported in P+G arm due to AEs.

Conclusions

Combination of P+G demonstrated numerically higher OS compared with G alone in tx-naïve pts with EGFR-mut advanced NS NSCLC. PFS was significantly prolonged with P+G and more pts experienced AEs in P+G vs G arm.

Clinical trial identification

NCT01469000.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Editorial Acknowledgement

The authors acknowledge Vinay Kumar Ranka for writing assistance on this abstract.

Disclosure

J.C.-H. Yang: Personal fees: Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech, Chugai, Astellas, MSD, Merck Serono, Pfizer, Novartis, Celgene, Merrimack, Yuhan Pharmaceuticals, BMS, Ono Pharmaceuticals, Daiichi Sankyo, AstraZeneca, Hansoh Pharmaceuticals, Takeda Pharmaceuticals, outside the submitted work. H. Murakami: Grants and personal fees: AstraZeneca; personal fees: Lilly Japan, Chugai Pharma, Boehringer Ingelheim, Pfizer, Taiho Pharmaceutical, Novartis, Bristol-Myers Squibb Japan, Ono Pharmaceutical, Merck Sharp & Dohme, outside the submitted work. K. Nakagawa: Grants and personal fees: AstraZeneca, during the conduct of the study; Grants and personal fees: MSD K.K., Astellas Pharma Inc, Novartis Pharma K.K., Chugai Pharmaceutical Co.,Ltd., Eli Lilly Japan K.K., Taiho Pharmaceutical Co.,Ltd, Ono Pharmaceutical Co., Ltd; Grants from A2 Healthcare Corp, inVentiv Health Japan, Daiichi Sankyo Co., Ltd., AbbVie Inc., Quintiles Inc., Icon Japan K.K., Takeda Pharmaceutical Co.,Ltd., EP-CRSU CO., LTD., Gritsone Oncology Inc., Linical Co.,Ltd., Eisai Co., Ltd., Parexel International Corp.; Personal fees: Clinical Trial Co., Ltd, Nippon Boehringer Ingelheim Co. Ltd., SymBio Pharmaceuticals Limited. X. Wnag: Employee: Eli Lilly and Company. S. Enatsu, T. Puri, M. Orlando: Other: Eli Lilly, outside the submitted work. All other authors have declared no conflicts of interest.

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Poster Discussion session - NSCLC, metastatic 1 Poster Discussion session

1382PD - Phase III Study of Gefitinib (G) versus Gefitinib+Carboplatin+Pemetrexed (GCP) as 1st-line Treatment for Patients (pts) with Advanced Non-Small Cell Lung Cancer (NSCLC) with EGFR Mutations (NEJ009)

Presentation Number
1382PD
Lecture Time
14:30 - 14:30
Speakers
  • Masahiro Seike (Tokyo, JP)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:00

Abstract

Background

Although EGFR-TKI alone has been a standard first-line treatment for pts with advanced NSCLC with EGFR mutations, our phase II study (NEJ005) showed promising efficacy of GCP. NEJ009, an open-label, randomized phase III study, was conducted to evaluate the superiority of GCP vs G in progression-free survival (PFS), PFS2, and overall survival (OS).

Methods

Pts with newly diagnosed stage III/IV/recurrent NSCLC harboring EGFR activating mutations (exon 19 deletion or exon 21 L858R) were randomized 1:1 to G 250 mg PO QD or GCP (G 250mg PO QD combined with carboplatin AUC 5 + pemetrexed 500mg/m2, every 3 weeks). The primary endpoints consisting of PFS, PFS2, and OS were sequentially analyzed according to a preplanned gate-keeping method. Secondary endpoints included objective response rate, safety, and quality of life.

Results

From Oct 2011 to Sep 215, 345 pts were enrolled and 342 pts (G 172, GCP 170) were evaluated. Baseline characteristics fairly well balanced between the arms. GCP demonstrated significantly better PFS compared to G as below. Although there was no difference in PFS2 between the arms, additional OS analysis (G 101 events vs GCP 83 events) revealed that median survival time of GCP was much longer than that of G (52.2 months vs 38.8 months, HR: 0.695, p = 0.013). Details of post-protocol treatments in both arms will be presented at the meeting.

Conclusions

NEJ009 was the first phase III study which evaluated the efficacy of a combination of EGFR-TKI and platinum doublet chemotherapy in untreated advanced NSCLC pts with EGFR mutations. Although GCP regimen failed to demonstrate its superiority in PFS2, it increased long survivors.

ITT populationGCP (N = 169)G (N = 172)
Median (months)Median (months)HR
PFS20.911.20.493
95%CI:18.0, 24.295%CI:9.0,13.495%CI:0.390, 0.623
P < 0.001
PFS220.921.10.891
95%CI:18.0,24.295%CI:17.9,24.995%CI: 0.708,1.122
P = 0.806
OS (additional analysis)52.238.80.695 (P = 0.013)

Legal entity responsible for the study

North East Japan Study Group (NEJ).

Funding

Has not received any funding.

Disclosure

M. Seike: Lecture fees: AstraZeneca, Eli Lilly, Taiho Pharmaceutical. A. Inoue: Lecture fees: AstraZeneca, Eli Lilly, Boehringer Ingelheim, MSD, Chugai, Pfizer. S. Sugawara: Lecture fees: AstraZeneca, Chugai Pharma, Nippon Boehringer Ingelheim, Taiho Pharmaceutical, Pfizer, Eli Lilly and Company, Novartis, Kyowa Hakko Kirin, Bristol-Myers Squibb, Ono Pharmaceutical, MSD K.K. S. Morita: Lecture fees: AstraZeneca, Eli Lilly. Y. Hosomi: Lecture fees: AstraZeneca, Taiho Pharmaceutical, Lilly, Chugai Phama, Ono Taiho Pharmaceutical, Bristol-Myers Squibb Japan, MSD. K. Takahashi: Lecture fees and research funding: AstraZeneca, Eli Lilly. Y. Fujita: Lecture fees: Chugai, Ono, Eli Lilly; Research funding: Taiho, Chugai, Eli Lilly, Pfizer Japan. K. Minato: Research funding: Taiho, Bristol-Myers Squibb, Quintiles. K. Kobayashi: Lecture fees: AstraZeneca, Chugai, Ono, Eli Lilly; Consulting or advisory role fee: AstraZeneca. T. Nukiwa: Lecture fees: Asahi-Kasei, Nippon Boehringer Ingelheim. All other authors have declared no conflicts of interest.

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Poster Discussion session - NSCLC, metastatic 1 Poster Discussion session

1383PD - An open-label, multicenter, phase 1 study of ABBV-399 (telisotuzumab vedotin, teliso-V) as monotherapy (T) and in combination with erlotinib (T+E) in non-small cell lung cancer (NSCLC)

Presentation Number
1383PD
Lecture Time
14:30 - 14:30
Speakers
  • Ross Camidge (Aurora, US)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:00

Abstract

Background

Teliso-V is a c-Met–targeted antibody and MMAE drug conjugate, with a t1/2 of ∼2–4 days. We updated data analyses of T schedule of administration (q2w vs q3w) and T+E in c-Met+ NSCLC pts.

Methods

T doses ranged from 2.4–3.0 mg/kg (dose expansion [DE] at 2.7 mg/kg) q3w or at doses from 1.6–2.2 mg/kg (DE at 1.9 mg/kg) q2w to pts with advanced c-Met + (IHC H-score ≥150) NSCLC and q3w at 2.7 mg/kg in combo with E 150 mg qd (NCT02099058). c-Met IHC staining was centrally assessed with the SP44 Ab (Ventana; Tucson, AZ). EGFR activating mutation (EGFR M+) status was defined per local report. PK sampling was performed.

Results

As of Feb 9, 2018, 50 pts received ≥1 dose of T; 8 of 23 (35%) pts on T+E were EGFR M+ and c-MET+. Rate of c-MET+ among screened NSCLC pts with adenocarcinoma and squamous (Sq) histologies was 64% and 42%, respectively. Monotherapy (q2w vs q3w) all grades (Gr; ≥40%) adverse events (AEs): fatigue (50% vs 59%), neuropathy (NP; 57% vs 23%), and nausea (36% vs 41%); Gr ≥ 3 (≥10%): anemia (7% vs 18%). All Gr T+E (≥20%): NP (39%), hypoalbuminemia (26%), dermatitis acneiform (26%)/rash (13%), pulmonary embolism (PE), diarrhea, and nausea (22%, each); Gr ≥ 3 (≥10%) AE: PE (22%). Median time to NP onset was 3.3 months (95% CI: 1.5–5.6) among 17 T-related NPs. Higher T trough concentrations that were observed with q2w than with q3w correlated with Gr ≥ 2 NP (p = 0.014) and indicated a trend of higher ORR (p = 0.202). See table for efficacy: T exposure data by histologies, T dosing, and EGFR M+ pts on T+E.

Conclusions

Safety profiles between T treatment schedules were comparable except for more NP for q2w schedule; potentially due to longer treatment duration. In the non-Sq subgroup a trend of better efficacy was observed with q2w than q3w; 1.9 mg/kg q2w was selected as the RP2D for T moving forward. Promising activity was seen for T+E in EGFR M+ and c-MET+ NSCLC and warrants continued evaluation.

Clinical trial identification

NCT02099058.

Legal entity responsible for the study

AbbVie Inc.

Funding

AbbVie Inc.

Editorial Acknowledgement

Medical writing support was provided by Mary L. Smith, PhD, CMPP, from TRM Oncology, Atlanta, GA, and funded by AbbVie.

Disclosure

J. Goldman: Research funding: AbbVie. E. Angevin: Consultant: Merck Sharp & Dohme, GlaxoSmithKline; Research funding: AbbVie, Roche, Sanofi; Travel, accommodations, expenses: AbbVie, Roche, and Sanofi. J. Strickler: Consultant: Amgen, Bayer, Boehringer Ingelheim, Celgene, Genentech; Research funding: AbbVie, Bayer, Exelixis, Gilead Sciences, MedImmune, OncoMed, Regeneron, Sanofi. D. Morgensztern: Consultant: Bristol-Myers Squibb, Celgene. T.M. Bauer: Consultant: Ignyta, Guardant Health, Loxo, Pfizer, Moderna Therapeutics; Research funding: Daiichi Sankyo, Medpacto, Inc., Incyte, Mirati Therapeutics, MedImmune, AbbVie, AstraZeneca, Leap Therapeutics, MabVax, Stemline Therapeutics, Merck, Lilly, GlaxoSmithKline, Novartis, Pfizer, Principia Biopharma, Genentech/Roche, Deciphera, Merrimack, Immunogen, Millennium, Ignyta, Calithera Biosciences, Kolltan Pharmaceuticals, Principia Biopharma, Peloton, Immunocore, Roche, Aileron Therapeutics, Bristol-Myers Squibb, Amgen, Moderna Therapeutics, Sanofi, Boehringer Ingelheim, Astellas Pharma, Five Prime Therapeutics, Jacobio. E.E. Vokes: Consultant: AbbVie, Amgen, Ariad, AstraZeneca, Bayer, Biolumina, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, EMD Serono, Genentech, Leidos, Novartis, Merck, Regeneron, Takeda, VentiRx. T. Yi, M. Motwani, A. Parikh, J. Wu: Employed and may own stock: AbbVie. K. Kelly: Consultant: AbbVie, AstraZeneca, Genentech, Janssen, Lilly, Merck; Travel, accommodation, expenses: AbbVie, AstraZeneca, Genentech, Janssen, Lilly, Merck; Honoraria: Merck; Research funding: AbbVie, Celgene, EMD Serono, Five Prime, Genentech, Lilly, Lycera, Novartis, Regeneron, Transgene. All other authors have declared no conflicts of interest.

T EGFR WT NSCLC
T+E EGFR M+ NSCLC (n = 8)
Sq + nSq (n = 37)Sq (n = 7)nSq
All (n = 30)q2w (n = 16)q3w (n = 14)
Objective response rate*, % (95% CI)24.3 (6.1–53.5)42.9 (9.9–81.6)20 (7.7–38.6)31 (11–59)7 (0–34)50 (15.7–84.3)
Median PFS, mo (95% CI)5.2 (2.7–8.0)6.4 (1.2–15.4)4.1 (1.6–8.8)5.2 (2.7–8.8)1.4 (1.2–NR)5.3 (1.4–NR)
Treatment duration, wk Median (range)10.4 (0.1–59.9)22.4 (3.1–57.1)10.1 (0.1–59.9)16.8 (0.1–59.9)3.2 (0.1–23)19.5 (3.1–39.1)
Duration of response, mo Median (95% CI)11.1 (3.1–11.1)4.8 (3.1–11.1)NR (6.2–NR)NR (6.2–NR)NR (NR–NR)NR (2.8–NR)

RECIST version 1.1. EGFR M+, epidermal growth factor receptor activating mutation; EGFR WT, epidermal growth factor receptor wildtype; NR, not reached; NSCLC, non-small cell lung cancer; nSq, non-squamous; PFS, progression-free survival; q2w, once every 14 days; q3w, once every 21 days; Sq, squamous; RECIST, Response Evaluation Criteria In Solid Tumors; T, teliso-V monotherapy; T+E, teliso-V plus erlotinib.

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Poster Discussion session - NSCLC, metastatic 1 Poster Discussion session

LBA61 - Phase II results for single-agent nazartinib (EGF816) in adult patients (pts) with treatment-naive EGFR-mutant non-small cell lung cancer (NSCLC)

Presentation Number
LBA61
Lecture Time
14:30 - 14:30
Speakers
  • Daniel Shao Weng S. Tan (Singapore, SG)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:00

Abstract

Background

Nazartinib (EGF816) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that selectively targets activating (L858R, ex19del) and resistance (T790M) mutants, while sparing wild type. In this phase I/II multicenter study in advanced EGFR-mutant NSCLC (NCT02108964), the recommended phase II dose was 150 mg once daily (QD). Phase II primary efficacy and safety data are presented.

Methods

Treatment-naive pts with NSCLC harboring activating EGFR mutations (L858R and/or ex19del) received oral nazartinib 150 mg QD on a continuous schedule. Primary objective was antitumor activity (overall response rate [ORR] per RECIST v1.1) per blinded independent review committee. Secondary objectives included characterization of safety/tolerability and pharmacokinetics.

Results

At data cutoff (22 March 2018), 45 pts were enrolled; median age 64 years, 62% Asian, 60% female, 58% ECOG PS 1, 18/45 pts (40%) had baseline brain metastases (BM). EGFR mutations were 56% ex19del, 40% L858R, 4% other. Of 45 pts, 12 discontinued nazartinib due to progressive disease (n = 9), adverse events (AEs; maculopapular rash [n = 1]), patient choice (n = 1), or death (n = 1). Median duration of exposure was 43.3 weeks. Frequent AEs (any grade ≥ 20%) regardless of causality were diarrhea (38%), maculopapular rash (31%), stomatitis (24%), cough (22%), decreased appetite (22%), pruritus (20%), and pyrexia (20%). The most frequent grade 3/4 AE (≥ 5%) regardless of cause was maculopapular rash (9%). ORR was 64% (29/45; 95% CI, 49%-78%), including 1 complete response. At data cutoff, responses were ongoing in 27/29 pts; 6-month duration of response rate was 91% (median NE), and 6-month progression-free survival and overall survival rates were 83% and 95%, respectively (medians NE). Disease control rate was 93%. In the 17 pts with baseline BM in nontarget lesions, 9 pts (53%) showed resolution of BM; 1/27 pts without baseline BMs had a new BM post-baseline.

Conclusions

Nazartinib demonstrated a tolerable safety profile and promising efficacy, with durable responses in treatment-naive pts with advanced EGFR-mutant NSCLC, including pts with baseline BM.

Clinical trial identification

EUDRACT number 2013-004482-14

NCT02108964

Release date: 07-Apr-2017

Editorial Acknowledgement

Editorial assistance was provided by Zareen Khan of ArticulateScience Ltd.

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Poster Discussion session - NSCLC, metastatic 1 Poster Discussion session

Invited Discussant LBA60, 1381PD, 1382PD, 1383PD and LBA61

Lecture Time
14:30 - 14:50
Speakers
  • Raffaele Califano (Manchester, GB)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:00
Poster Discussion session - NSCLC, metastatic 1 Poster Discussion session

Q&A led by Discussant

Lecture Time
14:50 - 15:00
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:00