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Mini Oral session

Mini Oral 2

Date
Fri, 31.03.2023
Time
08:15 - 09:15
Room
Auditorium 4
Chairs
  • M. C. Garassino (Chicago, United States of America)
  • N. Peled (Jerusalem, Israel)
Mini Oral session

114MO - First-line cemiplimab for locally advanced non-small cell lung cancer: Updated subgroup analyses from EMPOWER-Lung 1 and EMPOWER-Lung 3

Presentation Number
114MO
Lecture Time
08:15 - 08:20
Speakers
  • E. Kalinka (Lódz, Poland)
Session Name
Mini Oral 2 (ID 42)
Room
Auditorium 4
Date
Fri, 31.03.2023
Time
08:15 - 09:15
Authors
  • E. Kalinka (Lódz, Poland)
  • I. Bondarenko (Dnipro, Ukraine)
  • M. Gogishvili (Tbilisi, Georgia)
  • T. Melkadze (Tbilisi, Georgia)
  • A. Baramidze (Tbilisi, Georgia)
  • A. Sezer (Adana, Turkey)
  • T. Makharadze (Batumi, Georgia)
  • S. Kilickap (Istanbul, Turkey)
  • M. Gumus (Istanbul, Turkey)
  • K. D. Penkov (Saint-Petersburg, Russian Federation)
  • D. Giorgadze (Omsk, Russian Federation)
  • M. Özgüroglu (Istanbul, Turkey)
  • X. He (Tarrytown, United States of America)
  • J. Pouliot (Tarrytown, United States of America)
  • F. Seebach (Tarrytown, United States of America)
  • I. Lowy (Tarrytown, United States of America)
  • G. Gullo (Tarrytown, United States of America)
  • P. Rietschel (Tarrytown, United States of America)

Abstract

Background

Patients (pts) with unresectable locally advanced non-small cell lung cancer (laNSCLC) who are not candidates for concurrent chemoradiation have often been excluded from immunotherapy trials, and their care represent an unmet medical need. We report post hoc analyses of pts with laNSCLC who received cemiplimab (anti–programmed cell death-1) from two phase III clinical trials with long-term data.

Methods

EMPOWER-Lung 1 and EMPOWER-Lung 3 included pts with squamous or non-squamous NSCLC that was metastatic or locally advanced (not suitable for definitive concurrent chemoradiation) without EGFR, ALK or ROS1 genomic aberrations. In EMPOWER-Lung 1 pts were randomised 1:1 to first-line (1L) cemiplimab monotherapy or chemo for NSCLC with ≥50% programmed cell death-ligand 1 (PD-L1) expression. In EMPOWER-Lung 3 pts were randomised 2:1 to 1L cemiplimab + chemo or placebo + chemo regardless of PD-L1 expression level.

Results

In each trial, 15% of pts were treated for laNSCLC. In EMPOWER-Lung 1, at ∼3-year follow-up of pts with laNSCLC, 1L cemiplimab monotherapy led to a median overall survival (OS) of 26.1 vs 13.9 mo with chemo (HR: 0.67; 0.38–1.17; p = 0.1532). Progression-free survival (PFS) was 8.1 vs 6.2 mo (HR: 0.56; 0.34–0.95; p = 0.0286). Objective response rate (ORR) was 49% vs 31%. Median duration of response (DOR) was 18.8 vs 6.2 mo. In EMPOWER-Lung 3, at ∼2-year follow-up of pts with laNSCLC, greater efficacy was observed with 1L cemiplimab + chemo vs placebo + chemo. Median OS was 24.1 vs 13.8 mo (HR: 0.50; 0.27–0.95; p = 0.0293) and median PFS was 12.5 vs 6.2 mo (HR: 0.34; 0.19–0.61; p = 0.0002). ORR was 58% vs 29%. Median DOR was 27.8 vs 4.2 mo.

EMPOWER-Lung 1† (n = 565)EMPOWER-Lung 3 Part 2 (n = 466)
Subgroup with laNSCLCCemiplimab (n = 45) vs chemo (n = 42)Cemiplimab + chemo (n = 45) vs placebo + chemo (n = 24)
Study follow-up duration,‡ median (range), mo36.2 (24.4–53.7) vs 35.6 (24.3–53.6)28.7 (21.0–35.9) vs 29.3 (22.6–35.4)
OS median, mo26.1 vs 13.924.1 vs 13.8
OS HR (95% CI)0.67 (0.38–1.17); p = 0.15320.50 (0.27–0.95); p = 0.0293
PFS median, mo8.1 vs 6.212.5 vs 6.2
PFS HR (95% CI)0.56 (0.34–0.95); p = 0.02860.34 (0.19–0.61); p = 0.0002
ORR, %49 vs 3158 vs 29
Kaplan-Meier estimated DOR, median (95% CI), mo18.8 (6.4–NE) vs 6.2 (3.4–8.5)27.8 (13.1–27.8) vs 4.2 (3.0–10.3)

†PD-L1 ≥50% population. ‡From randomization to data cutoff.

Conclusions

Long-term follow-up data from EMPOWER-Lung studies continue to suggest clinical benefit of 1L cemiplimab as monotherapy or in combination with platinum-based chemo in pts with unresectable laNSCLC who are not candidates for definitive concurrent chemoradiation.

Clinical trial identification

NCT03088540 and NCT03409614.

Editorial acknowledgement

Medical writing support was provided by Rachel McGrandle, MSc, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc. and Sanofi. Responsibility for all opinions, conclusions, and data interpretation lies with the authors.

Legal entity responsible for the study

Regeneron Pharmaceuticals, Inc.

Funding

Regeneron Pharmaceuticals, Inc. and Sanofi.

Disclosure

E. Kalinka: Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Bristol-Meyers Squibb, Merck Sharp & Dohme, Nektar, Pfizer, Roche, Regeneron Pharmaceuticals, Inc. A. Sezer: Financial Interests, Institutional, Research Grant: Roche, Merck Sharp & Dohme, Merck Serono, AstraZeneca, Eli Lilly, Novartis, Johnson & Johnson, Regeneron Pharmaceuticals, Inc., Sanofi. M. Gumus: Financial Interests, Personal, Other, Honoraria: Roche, Merck Sharp & Dohme, Gen İlaç, Novartis. K.D. Penkov: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Merck Sharp & Dohme, Nektar, Pfizer, Regeneron Pharmaceuticals, Inc., Roche; Financial Interests, Personal, Advisory Role: Nektar. M. Özgüroğlu: Financial Interests, Personal, Other, Honoraria: Novartis, Roche, Janssen, Sanofi, Astellas; Financial Interests, Personal, Advisory Board: Janssen, Sanofi, Astellas; Financial Interests, Personal, Other, Travel support: Bristol-Myers Squibb, Janssen, AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca. X. He: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. J. Pouliot: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. F. Seebach: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. I. Lowy: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. G. Gullo: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. P. Rietschel: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.

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Mini Oral session

10MO - EMPOWER-Lung 1: Cemiplimab (CEMI) monotherapy as first-line (1L) treatment of patients (pts) with brain metastases from advanced non-small cell lung cancer (aNSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50% — 3-year update

Presentation Number
10MO
Lecture Time
08:20 - 08:25
Speakers
  • S. Kilickap (Istanbul, Turkey)
Session Name
Mini Oral 2 (ID 42)
Room
Auditorium 4
Date
Fri, 31.03.2023
Time
08:15 - 09:15
Authors
  • S. Kilickap (Istanbul, Turkey)
  • M. Özgüroglu (Istanbul, Turkey)
  • A. Sezer (Adana, Turkey)
  • M. Gumus (Istanbul, Turkey)
  • I. Bondarenko (Dnipro, Ukraine)
  • M. Gogishvili (Tbilisi, Georgia)
  • H. M. Türk (Istanbul, Turkey)
  • I. Cicin (Edirne, Turkey)
  • D. Bentsion (Sverdlovsk, Russian Federation)
  • O. A. Gladkov (Chelyabinsk, Russian Federation)
  • P. Clingan (Wollongong, Australia)
  • V. Sriuranpong (Bangkok, Thailand)
  • X. He (Tarrytown, United States of America)
  • J. Pouliot (Tarrytown, United States of America)
  • F. Seebach (Tarrytown, United States of America)
  • I. Lowy (Tarrytown, United States of America)
  • G. Gullo (Tarrytown, United States of America)
  • P. Rietschel (Tarrytown, United States of America)

Abstract

Background

In phase III EMPOWER-Lung 1 study, 1L CEMI monotherapy resulted in significantly longer OS and PFS versus chemotherapy (CHEMO) for pts with aNSCLC with no actionable genomic aberrations, whose tumours express PD-L1 ≥50%. The study included pts with treated, clinically stable, baseline brain metastases, a hard-to-treat and underrepresented population in clinical trials. We previously reported improved OS and PFS with 1L CEMI versus CHEMO for this subgroup. In this post hoc analysis, we report 3-year outcomes.

Methods

In EMPOWER-Lung 1, pts were randomised 1:1 to CEMI 350 mg IV Q3W or investigator's choice of CHEMO. The overall median follow-up duration from randomization to data cut-off (4 March 2022) was 37.1 months (mo; range 24.0–56.5). Here, we analyzed pts with treated, clinically stable brain metastases (radiological stability not required).

Results

In all, 69/565 (12.2%) pts with PD-L1 ≥50% had treated, clinically stable brain metastases at randomization. Baseline characteristics in CEMI (n = 34) vs CHEMO (n = 35) groups were: median age, 60.0 (range: 45–76) vs 62.0 (range: 48–77) yrs; male, 97.1% vs 82.9%; and non-squamous histology, 85.3% vs 74.3%. CEMI showed superior efficacy outcomes vs CHEMO: longer median OS (not reached vs 20.7 mo; HR = 0.42, 0.20–0.87), longer median PFS (12.5 vs 5.3 mo; HR = 0.34, 0.18–0.63), a higher ORR (55.9% vs 11.4%) and a longer median duration of response (31.7 mo vs 12.5 mo; table). After baseline, disease progression in brain occurred in 5 (14.7%) pts with CEMI vs 7 (20%) with CHEMO. Incidence of grade ≥3 TEAEs was 35.3% in the CEMI group vs 60.0% in CHEMO.

Clinical outcomesCemiplimab (n = 34)Chemotherapy (n = 35)HR (cemiplimab vs chemotherapy)
OS, mo, median (95% CI)NR (20.6–NE)20.7 (9.1–29.9)0.42 (0.20–0.87); P = 0.0168†
PFS, mo, median (95% CI)12.5 (6.1–33.5)5.3 (2.2–6.5)0.34 (0.18–0.63); P = 0.0004†
ORR, %, (95% CI)55.9 (37.9–72.8)11.4 (3.2–26.7)NA
Median (95% CI) duration of response (CR or PR), mo31.7 (14.7–NE)12.5 (4.4–NE)NA

Data cutoff date 4 March 2022.

Stratified log-rank test P-value.

CI, confidence interval; CR, complete response; ORR, objective response rate; OS, overall survival; mo, months; NA, not applicable; NE, not evaluable; NR, not reached; PFS, progression-free survival; PR, partial response.

Conclusions

Three-year follow up data shows durable clinical benefits and an acceptable safety profile with 1L CEMI monotherapy in subgroup analysis of pts with aNSCLC and brain metastases. CEMI is generally well tolerated in this subgroup.

Clinical trial identification

NCT03088540.

Editorial acknowledgement

Medical writing support was provided by John G Facciponte, PhD, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc. and Sanofi. Responsibility for all opinions, conclusions, and data interpretation lies with the authors.

Legal entity responsible for the study

Regeneron Pharmaceuticals, Inc.

Funding

Regeneron Pharmaceuticals, Inc. and Sanofi.

Disclosure

M. Özgüroğlu: Financial Interests, Personal, Advisory Role, Honoraria: Novartis, Roche, Janssen, Sanofi, Astellas; Financial Interests, Personal, Advisory Board: Janssen, Sanofi, Astellas; Financial Interests, Personal, Other, Travel support: Bristol-Myers Squibb, Janssen, AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca. A. Sezer: Financial Interests, Institutional, Research Grant: Roche, Merck Sharp & Dohme, Merck Serono, AstraZeneca, Eli Lilly, Novartis, Johnson & Johnson, Regeneron Pharmaceuticals, Inc., Sanofi. M. Gumus: Financial Interests, Institutional, Invited Speaker, Honoraria: Roche, Merck Sharp & Dohme, Gen İlaç, Novartis. I. Cicin: Financial Interests, Personal and Institutional, Advisory Role: Pfizer, Merck Sharp & Dohme Oncology, Roche, Novartis–Ipsen, Eli Lilly, Bristol-Myers Squibb, Servier, Abdi Ibrahim, Nobelpharma, AbbVie, Teva, Janssen Oncology; Financial Interests, Institutional, Invited Speaker, Speaker fees: Novartis, Roche, Bristol-Myers Squibb, Pfizer, Abdi Ibrahim. X. He: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. J. Pouliot: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. F. Seebach: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. I. Lowy: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Other, Patents pending: Regeneron Pharmaceuticals, Inc. G. Gullo: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. P. Rietschel: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Other, Patents pending: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.

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Mini Oral session

11MO - Final data from a phase II study (TACTI-002) of eftilagimod alpha (soluble LAG-3) and pembrolizumab in 2nd-line metastatic NSCLC pts resistant to PD-1/PD-L1 inhibitors

Presentation Number
11MO
Lecture Time
08:25 - 08:30
Speakers
  • M. Majem Tarruella (Barcelona, Spain)
Session Name
Mini Oral 2 (ID 42)
Room
Auditorium 4
Date
Fri, 31.03.2023
Time
08:15 - 09:15
Authors
  • M. Majem Tarruella (Barcelona, Spain)
  • M. D. Forster (London, United Kingdom)
  • M. G. Krebs (Manchester, United Kingdom)
  • J. Peguero (Houston, United States of America)
  • T. D. Clay (Subiaco, Australia)
  • E. Felip (Barcelona, Spain)
  • W. Iams (Tennessee, United States of America)
  • P. Roxburgh (Scotland, United Kingdom)
  • B. Doger de Spéville (Madrid, Spain)
  • P. Bajaj (Queensland, Australia)
  • C. Mueller (Leipzig, Germany)
  • F. Triebel (Paris, France)

Abstract

Background

Eftilagimod alpha (E), a soluble LAG-3 protein, acts as an MHC class II agonist triggering activation of antigen-presenting cells (APC) and CD8 T-cells. Stimulating APCs and subsequent T cell recruitment with efti may revert PD-1/PD-L1 resistance. We report updated results from Part B of the TACTI-002 trial: 2nd-line PD-1/PD-L1-resistant non-small cell lung carcinoma (NSCLC) patients (pts) treated with efti plus pembrolizumab (P).

Methods

Pts with metastatic NSCLC unselected for PD-L1 expression and with resistance to 1st-line PD-1/PD-L1 inhibitor-based therapy were enrolled. Primary endpoint (EP) was objective response rate (ORR) by iRECIST. Secondary EPs were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and tolerability. Post-hoc analysis included tumor growth kinetics (TGK). Pts received E (30 mg SC Q2W for eight 3-week cycles and then Q3W up to 1 yr) with P (200 mg IV Q3W up to 2 yrs). Imaging was performed every 9 wks and locally evaluated. PD-L1 TPS was assessed using IHC 22C3 kit.

Results

36 pts enrolled between Apr 2019 – Aug 2021. Median age was 67 yrs (46–84) and 61% were male. ECOG PS was 0 and 1 in 33% and 67% of pts. Pts had squamous (19%) and non-squamous (78%) histology. All PD-L1 subgroups were included: 39% with TPS <1% and 82% with TPS <50%. Pts received a PD-1/PD-L1 inhibitor alone (28%) or combined with platinum-based chemo (72%) as 1st-line therapy. Pts received median of 5 (2–35) P and 7 (2–22) E doses. ORR and DCR (iRECIST) was 8.3% and 33%. All PRs were confirmed with pts on study 19+ m. TGK analysis was performed on pts with data available on the same lesions from prior failed therapy and post-baseline. Vast majority (83%) of pts showed deceleration (50%) in tumor growth or shrinkage (33%) of target lesions. Median PFS was 2.1 months with PFS rate at 6 m of 25%. 44% were alive at 12 m with median OS of 9.7 m. Most common (>15%) adverse events were decreased appetite (33%), dyspnea (31%), cough (28%), asthenia (22%), fatigue (19%), arthralgia (17%) and weight decreased (17%).

Conclusions

Efti + pembrolizumab is safe and shows encouraging signs of antitumor activity in NSCLC pts resistant to PD-1/PD-L1 inhibitors, warranting further investigation.

Clinical trial identification

EudraCT 2018-001994-25, NCT03625323.

Legal entity responsible for the study

Immutep S.A.

Funding

Immutep S.A.

Disclosure

M. Majem: Other, Institutional, Other, Consulting or Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Helsinn Therapeutics, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, Tesaro, Sanofi, Janssen, Amgen; Other, Institutional, Funding: BMS, AstraZeneca, Roche (ALL Inst); Other, Institutional, Other, Travel, Accommodations, Expenses: AstraZeneca, Roche. M.D. Forster: Financial Interests, Personal, Advisory Board: Bayer, Merck, MSD, Novartis, Roche, Takeda, Ultrahuman, Transgene, Ixogen, Immunotep; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, MSD, Merck; Financial Interests, Institutional, Invited Speaker: StarPharma, Roche. M.G. Krebs: Financial Interests, Personal, Advisory Board: Bayer, Roche, Janssen, Guardant Health; Financial Interests, Personal, Invited Speaker: Roche, Janssen; Financial Interests, Institutional, Expert Testimony: AstraZeneca; Financial Interests, Institutional, Advisory Board: Seattle Genetics; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Blueprint, Astex, Bayer, BerGenBio, Carrick, Immutep, Janssen, Novartis, Nurix, Nuvalent, Pyramid Biosciences, Roche, Seattle Genetics, Turning Point Therapeutics; Financial Interests, Institutional, Research Grant: Roche, Novartis; Other, Personal, Other, Travel expenses for congress: Immutep, Janssen. J. Peguero: Financial Interests, Personal, Full or part-time Employment: Oncology Consultants; Financial Interests, Institutional, Leadership Role: Director, Research Department. T.D. Clay: Other, Personal, Other, Honoraria: Specialised Therapeutics, Wiley, Eli Lilly, Roche; Other, Personal, Stocks/Shares: ClinicIQ; Other, Personal, Advisory Board: AstraZeneca/MedImmune, Cipla, Foundation Medicine, Takeda, Merck KGaA, Merck/Pfizer, Ipsen; Other, Personal, Speaker's Bureau: AstraZeneca/MedImmune, MSD; Other, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca; Other, Institutional, Funding: Exelixis, Immutep, Clovis Oncology, MSD Oncology, Pfizer, Amgen, Daiichi Sankyo/AstraZeneca, AbbVie, Janssen Oncology, BeiGene, Bayer, BridgeBio Pharma, BMS GmbH & Co. KG. E. Felip: Other, Institutional, Other, Advisory Board and Invited Speaker: Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, F. Hoffman-La Roche, Janssen, Merck Sharp & Dohme, Merck Serono, Pfizer; Other, Institutional, Advisory Board: Bayer, BeiGene, Boehringer Ingelheim, Glaxo Smith Kline, Medical Trends, Peptomyc, Puma Biotechnology, Regeneron, Sanofi, Takeda; Other, Institutional, Invited Speaker: Peervoice, Springer, Touch Medical; Other, Institutional, Funding: Grant for Oncology Onnovation, MERCK Healthcare Kgaa, Fundación Merck Salud; Other, Institutional, Other, Independent Member Of The Board: Grífols. W. Iams: Other, Personal, Advisory Role: Genentech, Jazz Pharmaceuticals, G1 Therapeutics, Mirati, Bristol Myers Squibb, Takeda, Janssen; Financial Interests, Personal, Other, Consultancy: OncLive, Clinical Care Options, Chardan, Outcomes Insights, Cello Health, Curio Science. P. Roxburgh: Other, Institutional, Funding: AstraZeneca, Tesaro/GSK, Atrios; Other, Institutional, Other, Honoraria: AstraZeneca, Tesaro/GSK; Other, Institutional, Other, Funding to institution for role as site PI: Sierra oncology, PsiOxus, AstraZeneca, Starpharma, Forma Therapeutics, Iovance, Immutep, Bayer, Athenex, Replimune, Clovis, Nucana. C. Mueller: Financial Interests, Institutional, Full or part-time Employment: Immutep; Financial Interests, Personal, Stocks/Shares: Immutep. F. Triebel: Financial Interests, Institutional, Full or part-time Employment: Immutep SAS; Financial Interests, Personal, Stocks/Shares: Immutep Ltd; Other, Personal, Other, Patents, Royalties, Other Intellectual Property: Being an inventor on patents on LAG-3 owned by Immutep SAS. All other authors have declared no conflicts of interest.

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Mini Oral session

12MO - Patterns of response in metastatic (m) NSCLC after 2 and 4 cycles of chemotherapy (CT), alone or with durvalumab (D) ± tremelimumab (T), in the phase III POSEIDON study

Presentation Number
12MO
Lecture Time
08:30 - 08:35
Speakers
  • N. Reinmuth (Gauting, Germany)
Session Name
Mini Oral 2 (ID 42)
Room
Auditorium 4
Date
Fri, 31.03.2023
Time
08:15 - 09:15
Authors
  • N. Reinmuth (Gauting, Germany)
  • B. Cho (Seoul, Korea, Republic of)
  • A. Luft (St Petersburg, Russian Federation)
  • J. A. Alatorre Alexander (Mexico City, Mexico)
  • S. Lucien Geater (Songkhla, Thailand)
  • K. Laktionov (Moscow, Russian Federation)
  • S. Kim (Seoul, Korea, Republic of)
  • G. Ursol (Kropyvnytskyi, Ukraine)
  • M. Hussein (Leesburg, United States of America)
  • L. Lim Farah (London, United Kingdom)
  • C. Yang (Taoyuan City, Taiwan)
  • L. Araujo (Rio de Janeiro, Brazil)
  • H. Saito (Yokohama, Japan)
  • K. Barrett (Cambridge, United Kingdom)
  • C. Lowery (Gaithersburg, United States of America)
  • R. Tattersfield (Cambridge, United Kingdom)
  • S. Peters (Lausanne, Switzerland)
  • E. B. Garon (Los Angeles, United States of America)
  • T. Mok (Shatin, Hong Kong Special Administrative Region, China)
  • M. L. Johnson (Nashville, United States of America)

Abstract

Background

In POSEIDON, 1L T plus D and 4 cycles of platinum-based CT significantly improved PFS and OS vs CT in patients (pts) with EGFR/ALK wild-type mNSCLC leading to the approval of T+D+CT by the FDA; objective response rate (confirmed; 38.8% [95% CI, 33.6–44.3] and 41.5% [95% CI, 36.1–47.0] vs 24.4% [95% CI, 19.9–29.4]) and duration of response were also improved with both T+D+CT and D+CT vs CT. However, the relationship between number of CT cycles and patterns of response in pts with mNSCLC has not been fully established. Here we report outcomes in POSEIDON after 2 vs 4 CT cycles.

Methods

Pts (n = 1013) were randomised (1:1:1) to 1L T+D+CT, D+CT or CT. Exploratory analyses of objective response (intent-to-treat [ITT] population and subgroups with mutations [m] in STK11, KEAP1 or KRAS) and safety (safety population) were conducted after 2 vs 4 CT cycles (week 6 vs 12 scans, respectively).

Results

78%, 82% and 74% of pts who received T+D+CT, D+CT or CT completed 4 CT cycles. 560 pts had stable disease (SD) after cycle (C) 2. Of these, 22.9% had partial response (PR) after C4 (table). A similar trend was observed in pts with STK11m, KEAP1m or KRASm mNSCLC; in these pts, improvement appeared greatest with T+D+CT, although 95% CIs were wide and overlapping. Of 252 pts in the ITT with CR/PR after C2, 89.7% remained in response after C4 (table). Reductions in median target lesion size occurred between C2 and C4 in all arms (data will be presented). The frequency of grade 3/4 adverse events (AEs) and serious AEs originating in C1–2 and C3–4 was similar (data will be presented).

T+D+CTD+CTCTTotal
ITT
SD@C2 and PR@C4
 n/n47/18042/17939/201128/560
 % (95% CI)26.1 (19.9–33.2)23.5 (17.5–30.4)19.4 (14.2–25.6)22.9 (19.4–26.6)
CR/PR@C2 and CR/PR@C4
 n/n87/9687/9452/62226/252
 % (95% CI)90.6 (82.9–95.6)92.6 (85.3–97.0)83.9 (72.3–92.0)89.7 (85.2–93.1)
STK11m (NSQ)
SD@C2 and PR@C4
 n/n5/172/132/169/46
 % (95% CI)29.4 (10.3–56.0)15.4 (1.9–45.4)12.5 (1.6–38.3)19.6 (9.4–33.9)
KEAP1m (any histology)
SD@C2 and PR@C4
 n/n4/114/140/58/30
 % (95% CI)36.4 (10.9–69.2)28.6 (8.4–58.1)0.0 (0.0–52.2)26.7 (12.3–45.9)
KRASm (NSQ)
SD@C2 and PR@C4
 n/n13/319/332/2624/90
 % (95% CI)41.9 (24.5–60.9)27.3 (13.3–45.5)7.7 (0.9–25.1)26.7 (17.9–37.0)

NSQ, non-squamous.

Conclusions

These exploratory data support the use of 4 CT cycles, when given with T (limited course) and D (until progression), to optimise response and tumour shrinkage in pts with mNSCLC, including some harder to treat subgroups. Two further CT cycles did not meaningfully add to toxicity or compromise the ability to administer planned CT.

Clinical trial identification

NCT03164616.

Editorial acknowledgement

Medical writing support for the development of the abstract, under the direction of the authors, was provided by James Holland of Ashfield MedComms (Manchester, UK) an Inizio company, and funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

N. Reinmuth: Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Eli Lilly, Merck, MSD, Pfizer, Symphogen, Takeda; Financial Interests, Personal, Other, Consulting fee: AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Hoffmann-La Roche, Merck, MSD, Pfizer. B.C. Cho: Financial Interests, Personal, Full or part-time Employment: Yonsei University Health System; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Advisory Role: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc; Financial Interests, Personal, Member of the Board of Directors: Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Invited Speaker: ASCO, AstraZeneca, Guardant, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Medical Oncology, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer; Financial Interests, Personal, Other, Consultant: Abion, BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Medpacto, Blueprint medicines, RandBio, Hanmi; Financial Interests, Personal, Research Grant: MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Oncology, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Eli Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, Therapex, JINTSbio, Hanmi, CHA Bundang Medical Center; Financial Interests, Personal, Other, Royalties: Champions Oncology, Crown Bioscience, Imagen; Financial Interests, Personal, Other, Founder: DAAN Biotherapeutics. J.A. Alatorre Alexander: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Janssen, Eli Lilly, Takeda, BMS, MSD, Pfizer, Amgen; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Roche, Janssen, Eli Lilly, Takeda, BMS, MSD, Pfizer, Amgen. S. Lucien Geater: Financial Interests, Personal, Full or part-time Employment: Prince of Songkla University; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, Roche, Novartis, Samsung. S. Kim: Non-Financial Interests, Personal, Advisory Role: AstraZeneca, BMS, Boehringer Ingelheim, Novartis, Eli Lilly, Takeda, Therapex, and Yuhan; Non-Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Research Grant: Yuhan. M. Hussein: Financial Interests, Personal, Other, Honoraria: IntegraConnect, Coherus Biosciences, Athenex, Karyopharm Therapeutics, BMS, AstraZeneca, Mirati Therapeutics, Exelixis, BioPharma, AbbVie, Oncocyte, Aptitude Health. L.H. Araujo: Financial Interests, Personal, Advisory Board: MSD, Roche, AstraZeneca, BMS; Financial Interests, Personal, Other, Honoraria; speaker: Eli Lilly, MSD, Bristol Myers Squibb, AstraZeneca, Boehringer Ingelheim, Merck, Roche, Amgen; Financial Interests, Personal, Research Grant: Eli Lilly, Boehringer Ingelheim, MSD, Bristol Myers Squibb, Roche, Pfizer, AstraZeneca, Novartis, Merck. H. Saito: Financial Interests, Personal, Other, Honoraria: ONO Pharmaceutical, AstraZeneca, Bristol Myers Squibb, Chugai Pharmaceutical; Financial Interests, Personal, Research Grant: AstraZeneca, ONO Pharmaceutical, Bristol Myers Squibb, Chugai Pharmaceutical. K. Barrett: Financial Interests, Personal, Full or part-time Employment, Contractor: AstraZeneca; Financial Interests, Personal, Stocks/Shares: Takeda. C. Lowery: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. R. Tattersfield: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GlaxoSmithKline, Gilead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure; Financial Interests, Institutional, Invited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, PRIME, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, AstraZeneca, BMS, OncologyEducation, RMEI, Mirati; Financial Interests, Personal, Other, Associate Editor Annals of Oncology: Elsevier; Financial Interests, Institutional, Invited Speaker, MERMAID-1: AstraZeneca; Financial Interests, Institutional, Invited Speaker, MERMAID-2, POSEIDON, MYSTIC: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS; Financial Interests, Institutional, Invited Speaker, RELATIVITY 095: BMS; Financial Interests, Institutional, Invited Speaker, BGB-A317-A1217-301/AdvanTIG-301: BeiGene; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair ZEAL-1: GSK; Financial Interests, Institutional, Invited Speaker, Clinical Trial steering Committee PEARLS, MK-7684A: MSD; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering Committee SAPPHIRE: Mirati; Financial Interests, Institutional, Invited Speaker, LAGOON: PharmaMar; Financial Interests, Institutional, Invited Speaker, phase 1/2 trials: Phosplatin Therapeutics; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair Skyscraper-01; chair ALEX; steering committee BFAST; steering committee BEAT-Meso; steering committee ImPower-030, IMforte: Roche/Genentech; Financial Interests, Institutional, Invited Speaker, Phase 2 Inupadenant with chemo: iTeos; Non-Financial Interests, Personal, Officer, ESMO President 2020-2022: ESMO; Non-Financial Interests, Personal, Officer, Council Member & Scientific Committee Chair: ETOP/IBCSG Partners; Non-Financial Interests, Personal, Officer, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Other, Involved in Swiss politics: Swiss Political Activities; Non-Financial Interests, Personal, Officer, President and Council Member: Ballet Béjart Lausanne Foundation; Non-Financial Interests, Personal, Principal Investigator, Involved in academic trials: ETOP/EORTC/SAKK; Non-Financial Interests, Personal, Member: Association of Swiss Physicians FMH (CH), IASLC, ASCO, AACR; Non-Financial Interests, Personal, Leadership Role, ESMO President: ESMO; Non-Financial Interests, Personal, Member, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Leadership Role, Vice -President: SAMO; Non-Financial Interests, Personal, Member, Association of Swiss interns and residents: ASMAC/VSAO. E.B. Garon: Financial Interests, Personal, Advisory Role: AbbVie, ABL Bio, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Dracen Pharmaceuticals, EMD Serono, Eisai, Eli Lilly, Gilead, GlaxoSmithKline, Ipsen, Merck, Natera, Novartis, Personalis, Regeneron, Sanofi, Shionogi, and Xilio; Financial Interests, Personal, Research Grant: ABL Bio, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Dynavax Technologies, Eli Lilly, EMD Serono, Genentech, Iovance Biotherapeutics, Merck, Mirati Therapeutics, Neon, and Novartis. T.S.K. Mok: Financial Interests, Personal, Full or part-time Employment: The Chinese University of Hong Kong; Financial Interests, Personal, Stocks/Shares: AstraZeneca, Aurora Tele-Oncology Ltd., Biolidics Ltd., HutchMed, Prenetics; Financial Interests, Personal, Other, Stock option: Bowtie Life Insurance Co. Ltd., Lakeshore Biotech Ltd., Loxo-oncology, Lunit USA, Inc., Virtus Medical Group, D3 Bio; Financial Interests, Personal, Advisory Role: AbbVie Inc., ACEA Pharma, Amgen, AstraZeneca, BerGenBio ASA, Berry Oncology, Blueprint Medicines Corporation, Boehringer Ingelheim, Bowtie Life Insurance Co Ltd, Bristol Myers Squibb, C4 Therapeutics Inc, Covidien LP, CStone Pharmaceuticals, Curio Science, D3 Bio Ltd., Daiichi Sankyo Inc., Eisai, Fishawack Facilitate Ltd., G1 Therapeutics Inc., Gilead Sciences Inc., Gritstone Oncology, Inc., Guardant Health, geneDecode Co. Ltd. (uncompensated), Hengrui Therapeutics Inc., HutchMed, Ignyta Inc., Incyte Corporation, Inivata, IQVIA, Janssen, Lakeshore Biotech, Eli Lilly, Loxo-Oncology Inc., Lunit, Inc., Merck Serono, Merck Sharp & Dohme, Mirati Therapeutics Inc., MiRXES Group, Novartis, OrigiMed, Pfizer, Puma Biotechnology Inc., Roche/Genentech, Sanofi-Aventis R&D, SFJ Pharmaceutical, Simcere of America Inc., Takeda, Vertex Pharmaceuticals, Virtus Medical Group, Yuhan Corporation; Financial Interests, Personal, Member of the Board of Directors: AstraZeneca PLC, HutchMed, Aurora, Hong Kong Cancer Fund (HKCF) (2011 - Present) Hong Kong Cancer Therapy Society (HKCTS) (2004 – Present) International Association for the Study of Lung Cancer (IASLC) (2007–2019) St. Stephen's College & Prep. School (2017 – Present), Hong Kong Academy of Sciences (ASHK) (2022 – Present); Financial Interests, Personal, Invited Speaker: ACEA Pharma, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., Ltd., AstraZeneca (before 1/1/19), BeiGene, BI, BMS, Daiichi Sankyo, Daz Group, Fishawack Facilitate Ltd., InMed Medical Communication, Janssen Pharmaceutica NV, Jiahui Holdings Co. LTD, LiangYiHui Healthcare, Eli Lilly, Lucence Health Inc., MD Health Brazil, Medscape LLC, Merck Pharmaceuticals HK Ltd., Merck Sharp & Dohme, MiRXES, Novartis, OrigiMed Co. Ltd., P. Permanyer SL, PeerVoice, Physicians’ Education Resource, Pfizer, PrIME Oncology, Research to Practice, Roche Pharmaceuticals/Diagnostics/Foundation One, Sanofi-Aventis, Shanghai BeBirds Translation & Consulting Co., Ltd., Shanghai Promedican Pharmaceuticals Co., Ltd., Taiho Pharmaceutical Co. Ltd, Takeda Oncology, Touch Independent Medical Education Ltd; Financial Interests, Personal, Other, Contractor: AbbVie Inc., ACEA Pharma, Adagene, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., Ltd., AstraZeneca (before 1/1/19), Bayer Healthcare Pharmaceuticals Ltd., BeiGene, BerGenBio ASA, Berry Oncology, BI, Blueprint Medicines Corporation, BMS, Bowtie Life Insurance Company Limited, Bridge Biotherapeutics Inc., Covidien LP, C4 Therapeutics Inc., Cirina Ltd., CStone Pharmaceuticals, Curio Science, D3 Bio Ltd., Da Volterra, Daiichi Sankyo, Eisai, Elevation Oncology, F. Hoffmann-La Roche Ltd, Genentech, Fishawack Facilitate Ltd., G1 Therapeutics Inc., geneDecode Co., Ltd, Gilead Sciences, Inc. Gritstone Oncology, Inc., Guardant Health, Hengrui Therapeutics Inc., HutchMed, Ignyta, Inc., Incyte Corporation, Inivata, IQVIA, Janssen, Eli Lilly, Lunit USA, Inc., Loxo-Oncology, Lucence Health Inc., Medscape LLC/ WebMD, Merck Serono, MSD, Mirati Therapeutics Inc., MiRXES, MoreHealth, Novartis, Omega Therapeutics Inc., OrigiMed, OSE Immunotherapeutics, PeerVoice, Pfizer, PrIME Oncology, Puma Biotechnology Inc., Qiming Development (HK) Ltd., Roche Pharmaceuticals/ Diagnostics/ Foundation One, Sanofi-Aventis, SFJ Pharmaceutical Ltd., Simcere of America Inc., Synergy Research, Takeda Pharmaceuticals HK Ltd., Tigermed, Vertex Pharmaceuticals, Virtus Medical Group, Yuhan Corporation; Financial Interests, Personal, Research Grant: AstraZeneca, BMS, G1 Therapeutics, MSD, Merck Serono, Novartis, Pfizer, Roche, SFJ, Takeda, XCovery; Non-Financial Interests, Personal, Member of the Board of Directors: American Society of Clinical Oncology, Asian Thoracic Oncology Research Group (ATORG), Chinese Lung Cancer Research Foundation Limited (CLCRF), Chinese Society of Clinical Oncology (CSCO). M.L. Johnson: Financial Interests, Institutional, Advisory Role: AbbVie, Amgen, Arrivent, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Calithera Biosciences, Checkpoint Therapeutics, CytomX Therapeutics, Daiichi Sankyo, EcoR1, Editas Medicine, Eisai, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Ideaya Biosciences, iTeos, Janssen, Eli Lilly, Merck, Mirati Therapeutics, Molecular Axiom, Novartis, Oncorus, Pyramid Biosciences, Regeneron Pharmaceuticals, Revolution Medicines, Ribon Therapeutics, Sanofi-Aventis, SeaGen, Takeda Pharmaceuticals, Turning Point Therapeutics, VBL Therapeutics; Financial Interests, Institutional, Research Grant: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAtla, Black Diamond, Boehringer Ingelheim, Calithera Biosciences, Carisma Therapeutics, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Dynavax, Eli Lilly, Elicio Therapeutics, EMD Serono, EQRx, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchison MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunitas Therapeutics, Immunocore, Incyte, Janssen, Kadmon Pharmaceuticals, Kartos Therapeutics, Loxo Oncology, Lycera, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Palleon Pharmaceuticals, Pfizer, PMV Pharmaceuticals, Rain Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals/Birdie Biopharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, TMUNITY Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, Y-mAbs Therapeutics. All other authors have declared no conflicts of interest.

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Mini Oral session

Invited Discussant 114MO, 10MO, 11MO and 12MO

Lecture Time
08:35 - 08:45
Speakers
  • N. Peled (Jerusalem, Israel)
Session Name
Mini Oral 2 (ID 42)
Room
Auditorium 4
Date
Fri, 31.03.2023
Time
08:15 - 09:15
Authors
  • N. Peled (Jerusalem, Israel)
Mini Oral session

13MO - Safety and efficacy of tusamitamab ravtansine in combination with pembrolizumab ± chemotherapy in patients with CEACAM5-positive nonsquamous NSCLC (CARMEN-LC05 phase II study)

Presentation Number
13MO
Lecture Time
08:45 - 08:50
Speakers
  • L. Paz-Ares (Madrid, Spain)
Session Name
Mini Oral 2 (ID 42)
Room
Auditorium 4
Date
Fri, 31.03.2023
Time
08:15 - 09:15
Authors
  • N. Isambert (Poitiers, France)
  • T. Nagy (Budapest, Hungary)
  • M. Ravoire (Avignon, France)
  • D. Rodriguez-Abreu (Las Palmas de Gran Canaria, Spain)
  • J. L. Gonzalez-Larriba (Madrid, Spain)
  • C. H. Huang (Kansas City, United States of America)
  • L. Paz-Ares (Madrid, Spain)
  • J. Roubec (Vítkovice, Czech Republic)
  • F. Rey (Temuco, Chile)
  • G. Robinet (Brest, France)
  • A. Onn (Ramat Gan, Israel)
  • S. Shamai (Tel Aviv, Israel)
  • S. Bensfia (Cambridge, United States of America)
  • C. Soufflet (Vitry-sur-Seine, France)
  • A. Chevance (Chilly-Mazarin, France)
  • R. Veillon (Pessac, France)

Abstract

Background

Pembrolizumab (pembro) ± chemotherapy is currently standard-of-care (SoC) first-line treatment for advanced/metastatic nonsquamous (NSQ) non-small cell lung cancer (NSCLC) without EGFR, BRAF or ALK/ROS aberrations. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) expression is often higher in cancerous vs healthy lung cells. Tusamitamab ravtansine (tusa rav) is a humanized CEACAM5-specific antibody-drug conjugate linked to DM4. Tusa rav monotherapy has shown encouraging antitumor activity and safety in patients with heavily pretreated CEACAM5-positive NSQ NSCLC.

Methods

CARMEN-LC05 assessed safety and antitumor activity of tusa rav in combination with SoC regimens: with pembro [T2]; with pembro + platinum-based chemotherapy (pCT) [T3]; and with pembro + pCT + pemetrexed [T4] in patients with advanced/metastatic NSQ NSCLC with CEACAM5 intensity of ≥2+ in ≥1% of tumor cells by immunohistochemistry. Tusa rav was given IV Q3W at 150 or 170 mg/m2 in each treatment arm.

Results

As of Nov 28, 2022, 25 patients were treated for a median of 21 weeks (range 3–86); 12 (48%) were still on treatment. Dose-limiting toxicity of increased aspartate aminotransferase occurred in 1 patient in the T4 tusa rav 170 mg/m2 group. The most frequent treatment-emergent adverse events (TEAE) were nausea (44%), diarrhea (36%), and asthenia (32%); Grade ≥3 events occurred in 68%; and Grade 5 events in 16% in the treatment period (all unrelated to tusa rav). Corneal TEAEs of any grade occurred in 24% of patients; but only 1 (keratitis) was Grade ≥3 in the T2 tusa rav 170 mg/m2 group. Objective response rate (ORR) and disease control rate (DCR) for all patients were 40% and 88%, respectively.

Table of outcomesT2T3T4All
Tusa rav dose, mg/m2150170150170150170
Number of patients324112325
Any TEAE, n (%)3 (100)2 (100)4 (100)1 (100)12 (100)3 (100)25 (100)
Grade ≥3 TEAE, n (%)2 (66.7)2 (100)2 (50.0)1 (100)8 (66.7)2 (66.7)17 (68.0)
Grade 5 TEAE, n (%)00004 (33.3)04 (16.0)
TEAE leading to permanent discontinuation, n (%)0001 (100)3 (25.0)1 (33.3)5 (20.0)
Corneal TEAE, n (%)2 (66.7)1 (50.0)01 (100)1 (8.3)1 (33.3)6 (24.0)
ORR (confirmed complete response [CR] or partial response [PR]), n (%; 95% CI)3 (100)0 (0.0)2 (50.0)0 (0.0)3 (25.0)2 (66.7)10 (40.0; 21.1, 61.3)
DCR (confirmed CR, PR, or stable disease), n (%; 95% CI)3 (100)2 (100)4 (100)1 (100)9 (75.0)3 (100)22 (88.0; 68.8, 97.5)

Conclusions

Tusa rav combined with SoC showed encouraging antitumor activity across all treatment arms with a favorable safety profile, including in the T4 arm, and no new safety concerns, supporting ongoing evaluation of tusa rav.

Clinical trial identification

NCT04524689.

Editorial acknowledgement

Medical writing assistance was provided by Julian Martins, MA, MBBS, and Michael Stillman, PhD, inScience Communications, Springer Healthcare (Paris, France and New York, NY, respectively) and was funded by Sanofi.

Legal entity responsible for the study

Sanofi.

Funding

Sanofi.

Disclosure

N. Isambert: Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Other, Honoraria: BMS, Amgen, Daiichi Sankyo; Financial Interests, Personal, Other: Pfizer, Roche, PharmaMar, Novartis. D. Rodriguez-Abreu: Financial Interests, Personal, Advisory Board: BMS, MSD, Roche, AstraZeneca, Boehringer Ingelheim, Novartis, Eli Lilly; Financial Interests, Personal, Other, Honoraria: BMS, MSD, Roche, AstraZeneca, Boehringer Ingelheim, Novartis, Eli Lilly; Financial Interests, Personal, Speaker's Bureau: BMS, MSD, Roche, Novartis. J.L. Gonzalez-Larriba: Financial Interests, Personal, Full or part-time Employment: Ministry of Universities, Spanish National Health System; Financial Interests, Personal, Advisory Board: Janssen-Cilag, MSD Oncology, Bristol-Myers Squibb, Boehringer Ingelheim; Financial Interests, Personal, Research Grant: Miratti Therapeutics, AstraZeneca, Bayer, OncoMed, Astellas Pharma, Janssen-Cilag, Roche, AbbVie, Boehringer Ingelheim, Pfizer, PharmaMar, Bristol-Myers-Squibb, Novartis, Celgene, Ignyta; Financial Interests, Personal, Other, Honoraria: MSD Oncology, Pfizer, Astellas Pharma, Roche, Novartis, Janssen-Cilag, Bristol-Myers-Squibb, AstraZeneca; Financial Interests, Personal, Speaker's Bureau: MSD Oncology. C.H. Huang: Non-Financial Interests, Personal, Advisory Board: Jazz Pharmaceuticals; Financial Interests, Personal, Other, Self/Spouse: Vanguard Health Care Mutual Fund; Financial Interests, Institutional, Research Grant: Sanofi, Amgen, Novartis, Pfizer, Incyte, Genentech, Exelixis, Nektar, EpicentrRx. L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AstraZeneca, Eli Lilly, PharmaMar, BeiGene, Daiichi Sankyo, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme corp, BMS, Janssen-Cilag international NV, Novartis, Roche, Sanofi, Tesaro, Alkermes, Eli Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Other, Member: AACR, ASCO, ESMO; Financial Interests, Personal, Other, Foundation Board Member: AECC; Financial Interests, Personal, Other, President. ASEICA (Spanish Association of Cancer Research): ASEICA; Financial Interests, Personal, Other, Foundation president: ONCOSUR; Financial Interests, Personal, Other, member: Small Lung Cancer Group. S. Shamai: Financial Interests, Personal, Full or part-time Employment: Sanofi. S. Bensfia: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi. C. Soufflet: Financial Interests, Personal, Full or part-time Employment: Sanofi. A. Chevance: Financial Interests, Personal, Full or part-time Employment: Sanofi. R. Veillon: Financial Interests, Personal, Research Grant: Roche, Takeda, AbbVie, Merck; Financial Interests, Personal, Speaker's Bureau: MSD, BMS, Takeda, AstraZeneca, Janssen. All other authors have declared no conflicts of interest.

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Mini Oral session

14MO - Updated efficacy and safety of taletrectinib in patients (pts) with ROS1+ non-small cell lung cancer (NSCLC)

Presentation Number
14MO
Lecture Time
08:50 - 08:55
Speakers
  • W. Li (Shanghai, China)
Session Name
Mini Oral 2 (ID 42)
Room
Auditorium 4
Date
Fri, 31.03.2023
Time
08:15 - 09:15
Authors
  • W. Li (Shanghai, China)
  • K. Li (Changsha, China)
  • H. Fan (Zhengzhou, China)
  • Q. Yu (Nanning, China)
  • H. Wu (Zhengzhou, China)
  • Y. Wang (Chengdu, China)
  • X. Meng (Jinan, China)
  • J. Wu (Xiamen, China)
  • Z. Wang (Beijing, China)
  • Y. Liu (Shenyang, China)
  • X. Wang (Guangzhou, China)
  • X. Qin (Guangzhou, China)
  • K. Lu (Nanjing, China)
  • W. Zhuang (Fuzhou, China)
  • S. He (New York, United States of America)
  • P. A. Jänne (Boston, United States of America)
  • T. Seto (Fukuoka, Japan)
  • S. I. Ou (Orange, United States of America)
  • C. Zhou (Shanghai, China)

Abstract

Background

Taletrectinib is a potent, next-generation, CNS-active, ROS1 tyrosine kinase inhibitor (TKI) with selectivity over TRKB. In previous reports from TRUST-I, taletrectinib showed meaningful clinical efficacy and was well tolerated in pts with ROS1+ NSCLC (n = 109) regardless of crizotinib (CRZ) pretreatment status. We report updated efficacy and safety data with ∼1.5 yr follow-up.

Methods

TRUST-I is a multicenter, open-label, single-arm study with two cohorts: ROS1 TKI-naïve and CRZ-pretreated. Pts in both cohorts received taletrectinib 600 mg QD. Key study endpoints included IRC-confirmed ORR (cORR), DoR, disease control rate (DCR), PFS, and safety. A pooled analysis of ORR, PFS, and safety including pts from additional clinical trials was also conducted.

Results

In the 109 pts from TRUST-I (enrolled prior to Feb 2022) the median follow-up was 18.0 mo in TKI-naïve (n = 67) and 16.9 mo in CRZ-pretreated pts (n = 42). cORR was 92.5% in TKI-naïve and 52.6% in CRZ-pretreated pts (table). Median DoR (mDoR) and mPFS were not reached. Intracranial-ORR was 91.6%; ORR in pts with G2032R was 80.0%. In a pooled analysis with phase I studies, ORR was 89.5% and 50.0% for TKI-naïve and CRZ-pretreated pts, respectively; mPFS was 33.2 mo and 9.8 mo. In 178 pts treated at 600 mg QD, treatment-emergent adverse events (TEAEs) were 92.7%; most (64.0%) were grade 1–2. The most common TEAEs were increased AST (60.7%), increased ALT (55.6%), and diarrhea (55.6%). Neurological TEAEs (dizziness, 18.5%; dysgeusia, 12.4%) and discontinuations due to TEAEs (3.4%) were low. Further updated results will be presented.

Efficacy in pts treated with taletrectinib

TRUST-1ROS1 TKI-Naïve(n = 67)CRZ-Pretreated(n = 38)
Median follow-up18.016.9
(17.4–18.4)(11.7–18.0)
Confirmed ORR92.552.6
(83.4–97.5)(35.8–69.0)
Confirmed DCR95.581.6
(87.5–99.1)(65.7–92.3)
Median time to response,mo (Min,Max)1.41.4
(NE–NE)(1.3–1.4)
Pooled dataROS1 TKI-NaïveCRZ-Pretreated
(n = 78)(n = 46)
Confirmed ORRa89.550.0
(80.3–95.3)(34.6–65.4)
Median PFSa33.29.8
(23.5–NE)(5.6–18.4)

Data reported as mo (95% CI) unless specified.

Data from evaluable patients from a pooled analysis from phase I and II studies.

CRZ, crizotinib; DCR, disease control rate; NE, not evaluable; ORR, overall response rate; PFS, progression-free survival; TKI, tyrosine kinase inhibitor.

Conclusions

With additional follow-up, taletrectinib continued to demonstrate meaningful efficacy outcomes including high response rates, prolonged PFS, robust intracranial activity, activity against G2032R, and tolerable safety with low incidence of neurological AEs.

Clinical trial identification

NCT04395677.

Editorial acknowledgement

Medical writing and editorial assistance were provided by Arpita Kulshrestha of Peloton Advantage, LLC, an OPEN Health company, and funded by AnHeart Therapeutics, Inc.

Legal entity responsible for the study

AnHeart Therapeutics, Inc.

Funding

AnHeart Therapeutics, Inc.

Disclosure

S. He: Financial Interests, Personal, Other, Employment: AnHeart Therapeutics. T. Seto: Financial Interests, Institutional, Research Grant: AbbVie, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Kissei Pharmaceutical, MSD, Novartis Pharma, Pfizer Japan, Takeda Pharmaceutical; Financial Interests, Personal, Other, Employment: Precision Medicine Asia; Financial Interests, Personal, Speaker's Bureau, Honoraria for lectures: AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Covidien Japan, Daiichi Sankyo, Eli Lilly Japan, Kyowa Hakko Kirin, MSD, Mochida Pharmaceutical, Nippon Boehringer Ingelheim, Novartis Pharma, Ono Pharmaceutical, Pfizer Japan, Taiho Pharmaceutical, Takeda Pharmaceutical, Towa Pharmaceutical. C. Zhou: Financial Interests, Personal, Other, Consulting fees: Innovent Biologics Qilu, Hengrui, TopAlliance Biosciences Inc; Financial Interests, Personal, Speaker's Bureau, Payment or honoraria: Eli Lilly China, Sanofi, BI, Roche, MSD, Qilu, Hengrui, Innovent Biologics, C-Stone LUYE Pharma, TopAlliance Biosciences Inc, Amoy Diagnositics, AnHeart. All other authors have declared no conflicts of interest.

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Mini Oral session

15MO - Efficacy and ctDNA analysis in an updated cohort of patients with TRK fusion lung cancer treated with larotrectinib

Presentation Number
15MO
Lecture Time
08:55 - 09:00
Speakers
  • M. Hoejgaard (Copenhagen, Denmark)
Session Name
Mini Oral 2 (ID 42)
Room
Auditorium 4
Date
Fri, 31.03.2023
Time
08:15 - 09:15
Authors
  • M. Hoejgaard (Copenhagen, Denmark)
  • A. Drilon (New York, United States of America)
  • J. J. Lin (Boston, United States of America)
  • S. Kummar (Portland, United States of America)
  • D. Tan (Singapore, Singapore)
  • J. Patel (Chicago, United States of America)
  • S. Leyvraz (Berlin, Germany)
  • V. Moreno Garcia (Madrid, Spain)
  • L. S. Rosen (Santa Monica, United States of America)
  • B. Solomon (Sioux Falls, United States of America)
  • J. Yachnin (Solna, Sweden)
  • Y. Liu (Chengdu, China)
  • M. Dai (Taipei City, Taiwan)
  • R. Norenberg (Essen, Germany)
  • D. Burcoveanu (Basel, Switzerland)
  • L. Yun (Mississauga, Canada)
  • G. Beckmann (Berlin, Germany)
  • C. E. Mussi (Milan, Italy)
  • L. Shen (Beijing, China)

Abstract

Background

Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers in various cancers, including lung cancer. Larotrectinib, a highly selective, central nervous system (CNS)-active tropomyosin receptor kinase (TRK) inhibitor, demonstrated a 73% objective response rate (ORR) in 15 patients (pts) with TRK fusion lung cancer (Drilon et al. JCO Precis Oncol 2022). We report efficacy and safety with circulating tumour DNA (ctDNA) analysis in pts with TRK fusion lung cancer treated with larotrectinib.

Methods

Pts treated with larotrectinib in 2 clinical trials were analysed. NTRK gene fusions were determined by local testing before enrolment. Larotrectinib was administered at 100 mg twice daily. Response was assessed by an independent review committee (IRC) per RECIST v1.1. ctDNA was analysed using Guardant360 and GuardantOMNI.

Results

As of 20 July 2021, 26 pts (12 pts with CNS metastases) were enrolled. Among 23 pts (10 pts with CNS metastases) evaluable per IRC, ORR was 83% (95% confidence interval [CI] 61–95; 2 complete response, 17 partial response, 4 stable disease). Median duration of response (DoR) was not reached (95% CI 9.5–not estimable [NE]), with a 12-month DoR rate of 72%. Median progression-free survival was not reached (95% CI 9.9–NE). Median overall survival was 40.7 months (95% CI 19.4–NE). Treatment-related adverse events were mostly Grade 1–2. ctDNA data were available for 14 pts. ctDNA analysis detected NTRK gene fusions in 6 of the 14 pts at treatment start. Assessment of baseline co-occurring mutations revealed the inclusion of 3 patients with mutation-positive NSCLC who had failed prior anti-EGFR therapy. By the data cut-off, 6 pts had progressed, with ctDNA data available for 5 pts. Potential acquired mutations were identified in 3 pts.

Conclusions

Larotrectinib demonstrated durable responses, extended survival benefit, and a favourable safety profile in patients with advanced lung cancer harbouring NTRK gene fusions, including those with treatment-naive NSCLC or with prior EGFR inhibitor therapy. ctDNA next-generation sequencing represents a promising technology to test NTRK gene fusions or resistance mutations.

Clinical trial identification

NCT02122913, NCT02576431.

Editorial acknowledgement

Editorial assistance was provided by Anastasija Pesevska, PharmD, and Joe Alling, BSc, (Scion, London UK) funded by Bayer HealthCare Pharmaceuticals, Inc.

Legal entity responsible for the study

Bayer Healthcare Pharmaceuticals Inc. and Loxo Oncology.

Funding

These studies were funded by Bayer HealthCare Pharmaceuticals, Inc., and Loxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly and Company.

Disclosure

M. Hoejgaard: Financial Interests, Personal, Other, Advisory role for various diagnostic companies/investors: LingoMedical; Financial Interests, Personal, Stocks/Shares, Stocks, <20000USD: Bavarian Nordic, Pacific Biosciences, Illumina Inc.; Financial Interests, Personal, Stocks/Shares, stocks<20000USD: Agilent; Financial Interests, Institutional, Funding: Roche; Non-Financial Interests, Personal, Principal Investigator, TRESR trial and MYTHIC trial: Repare Therapeutics; Non-Financial Interests, Personal, Principal Investigator, AMG160 master protocol and Bemarituzumab trial: Amgen; Non-Financial Interests, Personal, Principal Investigator, INC93318-122: Incyte Cooperation; Non-Financial Interests, Personal, Principal Investigator, KN-4802 trial: Kinnate Biopharma; Other, Personal, Other, Board member, tumor agnostic board. Public service: Danish Medicines Council. A. Drilon: Financial Interests, Personal, Advisory Board: Ignyta/Genentech/Roche, Loxo/Bayer/Eli Lilly, Takeda/Ariad/Millennium, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Helsinn, BeiGene, BerGenBio, Hengrui Therapeutics, Exelixis, Tyra Biosciences, Verastem Oncology, MORE Health, AbbVie, 14ner/Elevation Oncology, Remedica Ltd., ArcherDX, Monopteros, Novartis, EMD Serono, Melendi, Liberum, Repare RX, Amgen, Janssen, EcoR1, Monte Rosa; Financial Interests, Personal, Other, CME: Medscape, Onclive, PeerVoice, Physicians Education Resources, Targeted Oncology, Research to Practice, PeerView Institute, Paradigm Medical Communications, WebMD, MJH Life Sciences, Med Learning, Imedex, Answers in CME, Medscape, Clinical Care Options, AiCME; Financial Interests, Personal, Other, CME, Consulting: Axis; Financial Interests, Personal, Other, Consulting: Nuvalent, Merus, EPG Health, mBrace, Harborside Nexus, Ology, TouchIME, Entos, Treeline Bio, Prelude, Applied Pharmaceutical Science, Inc; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, Remedica Ltd, RV More; Financial Interests, Personal, Stocks/Shares: Treeline Biosciences; Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Personal, Other, stocks: mBrace; Financial Interests, Institutional, Funding, Research funding: Pfizer, Exelixis, GlaxoSmithKline, Teva, Taiho, PharmaMar; Financial Interests, Personal, Funding, Research: Foundation Medicine; Non-Financial Interests, Personal, Member: ASCO, AACR, IASLC; Other, Personal, Other, Food/Beverage: Merck, PUMA, Merus; Other, Personal, Other, Other: Boehringer Ingelheim. J.J. Lin: Financial Interests, Personal, Other, Consulting: Turning Point Therapeutics, Nuvalent, Elevation Oncology, C4 Therapeutics, Bayer, Novartis, Mirati Therapeutics; Financial Interests, Personal, Advisory Board, Consulting: Blueprint Medicines, Genentech; Financial Interests, Personal, Other, Honorarium, travel: Pfizer; Financial Interests, Institutional, Invited Speaker: Turning Point Therapeutics, Neon Therapeutics, Relay Therapeutics, Bayer, Elevation Oncology, Roche/Genentech, Novartis, Hengrui Therapeutics, Pfizer, Nuvalent. S. Kummar: Financial Interests, Personal, Advisory Board: Bayer, Gilead, Mundibiopharma, Boehringer Ingelheim, Springworks Theraepeutics, HarbourBiomed, Boehringer Ingelheim, Oxford BioTherapeutics; Financial Interests, Personal, Advisory Board, Spouse: Cadila Pharmaceuticals; Financial Interests, Personal, Other, Chair, DSMC: Mirati; Financial Interests, Personal, Ownership Interest: Pahtomiq; Financial Interests, Personal, Other, co-founder: Pathomiq; Financial Interests, Institutional, Invited Speaker: ADC Therapeutics, Pionyr Therapeutics, Eisai, Bristol Myers Squibb, Syndax, SeaGen, ORIC, EMD Serono, Genome & Company, Moderna, Amgen, ASTX Therapeutics, PMV Pharmaceuticals, Elevation Oncology, VelosBio Inc, Gilead, Day One Biopharmaceuticals, Vincerx Pharma, Inc. D.S.W. Tan: Financial Interests, Personal, Advisory Board: Amgen, Novartis, Boehringer Ingelheim, C4 Therapeutics, AstraZeneca, GSK, Takeda, Eisai, Guardant, Merck, Pfizer, Roche; Financial Interests, Institutional, Research Grant: AstraZeneca, Amgen, Pfizer, ACM Biolabs; Financial Interests, Personal, Invited Speaker: Novartis. J. Patel: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, Takeda; Financial Interests, Personal, Advisory Role: Eli Lilly. S. Leyvraz: Financial Interests, Personal, Advisory Board: Bayer. V. Moreno Garcia: Financial Interests, Personal, Advisory Board: BMS, Janssen, Roche, Basilea, Bayer; Financial Interests, Personal, Full or part-time Employment: START; Non-Financial Interests, Personal, Principal Investigator, AbbVie, AceaBio, Adaptimmune, ADC Therapeutics, Aduro, Agenus, Amcure, Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BioInvent International AB, BMS, Boehringer Ingelheim, Boston, Celgene, Daiichi Sankyo, Debiopharm, Eisai, e-Terapeutics, Exelisis, Forma Therapeutics, Genmab, GSK, Harpoon, Hutchison, Immutep, Incyte, Inovio, Iovance, Janssen, Kyowa Kirin, Eli Lilly, Loxo, MedSir, Menarini, Merck, Merus, Millennium, MSD, Nanobiotix, Nektar, Novartis, Odonate Therapeutics, Pfizer, Pharma Mar, PharmaMar, Principia, PsiOxus, Puma, Regeneron, Rigontec, Roche, Sanofi, Sierra Oncology, Synthon, Taiho, Takeda, Tesaro, Transgene, Turning Point Therapeutics, Upshersmith.: Multiple. L.S. Rosen: Financial Interests, Institutional, Research Grant: Bayer. B. Solomon: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer; Financial Interests, Institutional, Invited Speaker: Daiichi-Sankyo, Iovance, GSK, Mirati, ImmunityBio, AstraZeneca, Amgen; Non-Financial Interests, Personal, Member: ASCO, AACR, ESMO. R. Norenberg: Financial Interests, Personal, Full or part-time Employment: Bayer. D. Burcoveanu: Financial Interests, Personal, Full or part-time Employment: Bayer. L. Yun: Financial Interests, Personal, Full or part-time Employment: Bayer. G. Beckmann: Financial Interests, Personal, Full or part-time Employment: Bayer. C.E. Mussi: Financial Interests, Personal, Full or part-time Employment: Bayer. L. Shen: Financial Interests, Institutional, Research Grant: Beijing Xiantong Biomedical Technology Co., Ltd, Qilu Pharmaceutical Co., Ltd, Zaiding Pharmaceutical (Shanghai) Co., Ltd, Jacobio Pharmaceuticals Co., Ltd, Beihai Kangcheng (Beijing) Medical Technology Co., Ltd.; Financial Interests, Personal, Advisory Board: MSD, Merck, Boehringer Ingelheim, Harbour; Financial Interests, Personal, Invited Speaker: Hutchison Whampoa, Hengrui,, Zai Lab, CStone Pharmaceuticals. All other authors have declared no conflicts of interest.

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Mini Oral session

16MO - Clinical impact of plasma EGFR analysis: Results from the ETOP-BOOSTER randomized phase II trial

Presentation Number
16MO
Lecture Time
09:00 - 09:05
Speakers
  • R. A. Soo (Singapore, Singapore)
Session Name
Mini Oral 2 (ID 42)
Room
Auditorium 4
Date
Fri, 31.03.2023
Time
08:15 - 09:15
Authors
  • R. A. Soo (Singapore, Singapore)
  • U. Dafni (Athens, Greece)
  • J. Han (Goyang, Korea, Republic of)
  • B. Cho (Seoul, Korea, Republic of)
  • E. Nadal (L'Hospitalet de Llobregat, Spain)
  • C. Yeo (Singapore, Singapore)
  • E. Carcereny (Badalona, Spain)
  • J. De Castro (Madrid, Spain)
  • M. Sala Gonzalez (Bilbao, Spain)
  • L. Coate (Limerick, Ireland)
  • M. Provencio Pulla (Majadahonda, Spain)
  • C. Britschgi (Zurich, Switzerland)
  • P. Vagenknecht (Bern, Switzerland)
  • G. Dimopoulou (Athens, Greece)
  • R. Kammler (Bern, Switzerland)
  • S. P. Finn (Dublin, Ireland)
  • S. Peters (Lausanne, Switzerland)
  • R. Stahel (Bern, Switzerland)
  • F. Etop 10-16 Booster Collaborators (Bern, Switzerland)

Abstract

Background

The ETOP-BOOSTER study explored the addition of bevacizumab to osimertinib as 2nd-line treatment in patients with pathologically confirmed advanced NSCLC harboring common sensitising EGFR (70% Exon 19 deletion; 30% Exon 21 L858R) and acquired EGFR T790M mutations (mt) and reported no difference in progression-free survival (PFS). An interaction of treatment outcomes by smoking status was previously identified. Pre-specified exploratory analysis of serial plasma samples using next generation sequencing (NGS) is reported.

Methods

Plasma circulating tumour DNA (ctDNA) analysis was conducted using Guardant360® on samples collected prospectively at baseline (BL), week 9 (w9) and at disease progression (PD). Multivariable Cox models, including interaction of treatment with smoking history, plasma EGFR T790M and TP53 mt at BL and longitudinally, and tumour EGFRmt status were analysed to assess their effect on outcome.

Results

From the 155 randomised patients, 136 (87%) had available blood samples at BL (68 in each arm), 110 (71%) at w9 and 65 (42%) at PD for plasma NGS analysis. EGFR T790M mt was detected in 71% (97/136) of BL samples and was not associated with PFS (table). At w9, EGFR T790M mt was undetected in 91% (of 80 available, initially mt, cases), while at PD it was present in 34% (of 47 cases available). Smoking status was found to be predictive for PFS (interaction p = 0.046), however it was not associated with TP53 mt, which was detected in 63% of BL samples. BL TP53 mt and tissue EGFR Exon 21 L858R were each found to be poor prognostic factors for PFS and overall survival independent of treatment.

Median PFS (95%CI) months, log-rank p
BEV-OSIOSIWhole cohort
BL EGFR T790M mt status (int p = 0.29)
D – 9714.9 (9.1–17)9.9 (5.5–16.7)12.4 (8.4–16.4)
ND – 3916.5 (8.1–26.9) p = 0.1513.4 (4.1–18.7) p = 0.9714.4 (8.1–20.5) p = 0.32
EGFR T790M at BL/w9 (int p = 0.037)
D at BL/9w – 7NR (6.3–NE)2.1 (0–15.1)3.9 (0–15.1)
D at BL; not at 9w –7313.3 (8.3–15.9)9.0 (4.1–18.6)10.5 (7.8–14.6)
ND at BL/9w – 277.1 (2.4–24.5) p = 0.397.5 (0.9–12.3) p = 0.0517.5 (4.1–12.3) p = 0.82
BL TP53 mt status (int p = 0.67)
D – 8610.4 (6.2–16.4)8.1 (4.2–12.4)9.4 (6.2–12.4)
ND – 5020.6 (14.1–26.6) p = 0.05418.6 (6.2–25.1) p = 0.02618.7 (14.4–24.4) p = 0.0033

Conclusions

The interaction of treatment with smoking, was confirmed for PFS in the current evaluation, and was not found to be driven by the presence of TP53 or EGFR T790M mt. BL TP53 mt and EGFR Exon 21 L858R were associated with poor outcome.

Clinical trial identification

EudraCT 2016-002029-12/ETOP 10-16 BOOSTER.

Legal entity responsible for the study

ETOP IBCSG Partners Foundation.

Funding

Has not received any funding.

Disclosure

R.A. Soo: Other, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Janssen, Eli Lilly, Merck, Merck Serono, Novartis, Pfizer, Puma, Roche, Taiho, Takeda, Thermo Fisher, Yuhan; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim. U. Dafni: Financial Interests, Personal, Other, Member of the Tumor Agnostic Evidence Generation working Group: Roche. J. Han: Financial Interests, Institutional, Research Grant: Roche, Ono, Pfizer, Takeda; Other, Personal, Advisory Board: BMS, Merck, Novartis, Pfizer, Takeda, Abion, Jint Bio, Janssen; Financial Interests, Personal, Funding, Honoraria: AstraZeneca, Takeda, Merck, Pfizer, Novartis, Yuhan, Ingenium Therapeutics, Onecure Gen, Janssen. B.C. Cho: Financial Interests, Personal, Other, Consulting role: Abion, BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Janssen; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc; Financial Interests, Personal, Other, Advisory role: Medpacto, Blueprint medicines, RandBio, Hanmi; Financial Interests, Personal, Invited Speaker: Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Royalties: Champions Oncology, Crown Bioscience, Imagen; Financial Interests, Institutional, Research Grant: MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Eli Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, Therapex, JINTSbio, Hanmi, CHA Bundang Medical Center; Other, Personal, Other, Founder: DAAN Biotherapeutics. E. Nadal: Financial Interests, Institutional, Research Grant: Roche, Pfizer, Merck-Serono, Bristol Myers Squibb, Nanostring; Non-Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Merck-Serono, Pfizer, Eli Lilly, Amgen, Boehringer Ingelheim, AstraZeneca, Takeda, Janssen, Daiichi-Sankyo, Sanofi, Bayer. E. Carcereny: Other, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Novartis, Roche, Takeda; Other, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Novartis, Pfizer, Roche, Takeda; Financial Interests, Institutional, Research Grant: Merck; Other, Personal, Other: Bristol-Myers Squibb, Pfizer, Roche, Takeda. M.A. Sala Gonzalez: Non-Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Roche, PharmaMar; Financial Interests, Personal, Funding, Meeting, Travel: Roche; Financial Interests, Personal, Funding, Meeting, Travel: Takeda; Financial Interests, Personal, Invited Speaker, Honoraria: Roche, PharmaMar, Takeda. M. Provencio Pulla: Financial Interests, Institutional, Research Grant: BMS, AstraZeneca, Roche, Takeda, Pfizer, Janssen; Other, Personal, Invited Speaker, Honoraria: BMS, AstraZeneca, Takeda, Pfizer, MSD, Roche. C. Britschgi: Financial Interests, Personal, Advisory Role: AstraZeneca, Pfizer, Roche, Takeda, Janssen-Cilag, Boehringer Ingelheim, Merck KGaA, Sanofi; Other, Personal, Funding, Travel, Meeting: AstraZeneca; Financial Interests, Personal, Funding, Travel, Meeting: Takeda. R. Kammler: Non-Financial Interests, Personal, Leadership Role: ESBB. S.P. Finn: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Bayer, BMS, Merck, Roche, Takeda. S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GlaxoSmithKline, Gilhead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure; Financial Interests, Institutional, Invited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, PRIME, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, BMS, AstraZeneca, OncologyEducation, RMEI, Mirati; Financial Interests, Personal, Other, Associate Editor Annals of Oncology: Elsevier; Financial Interests, Institutional, Invited Speaker, MERMAID-1: AstraZeneca; Financial Interests, Institutional, Invited Speaker, MERMAID-2, POSEIDON, MYSTIC: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS; Financial Interests, Institutional, Invited Speaker, RELATIVITY 095: BMS; Financial Interests, Institutional, Invited Speaker, BGB-A317-A1217-301/AdvanTIG-301: BeiGene; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair ZEAL-1: GSK; Financial Interests, Institutional, Invited Speaker, Clinical Trial steering Committee PEARLS, MK-7684A: MSD; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering Committee SAPPHIRE: Mirati; Financial Interests, Institutional, Invited Speaker, LAGOON: Pharma Mar; Financial Interests, Institutional, Invited Speaker, phase 1/2 trials: Phosplatin Therapeutics; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair Skyscraper-01; chair ALEX; steering committee BFAST; steering committee BEAT-Meso; steering committee ImPower-030, IMforte: Roche/Genentech; Financial Interests, Institutional, Invited Speaker, Phase 2 Inupadenant with chemo: iTeos; Non-Financial Interests, Personal, Officer, ESMO President 2020–2022: ESMO; Non-Financial Interests, Personal, Officer, Council Member & Scientific Committee Chair: ETOP/IBCSG Partners; Non-Financial Interests, Personal, Officer, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Other, Involved in Swiss politics: Swiss Political Activities; Non-Financial Interests, Personal, Officer, President and Council Member: Ballet Béjart Lausanne Foundation; Non-Financial Interests, Personal, Principal Investigator, Involved in academic trials: ETOP/EORTC/SAKK; Non-Financial Interests, Personal, Member: Association of Swiss Physicians FMH (CH), ASCO, AACR, IASLC; Non-Financial Interests, Personal, Leadership Role, ESMO President: ESMO; Non-Financial Interests, Personal, Member, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Leadership Role, Vice-President: SAMO; Non-Financial Interests, Personal, Member, Association of Swiss interns and residents: ASMAC/VSAO. R.A. Stahel: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Blueprint, Boehringer Ingelheim, GSK, MSD, Novartis, Roche, BMS; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Janssen, MSD, Pfizer, Roche, Sandoz, Seattle Genetics, Takeda, Boehringer Ingelheim, GSK; Financial Interests, Personal, Other, DMC: Takeda; Financial Interests, Personal, Other, Editor in Chief: Lung Cancer; Financial Interests, Personal, Other, Editor: CTR; Financial Interests, Institutional, Research Grant, ETOP study: Roche, AstraZeneca, BMS, MSD, Pfizer, Mirati, Janssen; Financial Interests, Institutional, Research Grant, IBCSG study: Novartis, Ipsen, Pierre Fabre, MSD, Pfizer, Roche, AstraZeneca, Celgene; Non-Financial Interests, Personal, Invited Speaker, President Foundation Council: IBCSG, ETOP. All other authors have declared no conflicts of interest.

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Mini Oral session

Invited Discussant 13MO, 14MO, 15MO and 16MO

Lecture Time
09:05 - 09:15
Speakers
  • M. C. Garassino (Chicago, United States of America)
Session Name
Mini Oral 2 (ID 42)
Room
Auditorium 4
Date
Fri, 31.03.2023
Time
08:15 - 09:15
Authors
  • M. C. Garassino (Chicago, United States of America)