All times are listed in CEST (Central European Summer Time)
- Marina C. Garassino (Chicago, United States of America)
- Yi-Long Wu (Guangzhou, China)
LBA63 - SAPPHIRE: Phase III study of sitravatinib plus nivolumab versus docetaxel in patients with previously treated advanced non-squamous non-small cell lung cancer (NSCLC)
- Hossein Borghaei (Philadelphia, United States of America)
Abstract
Background
Checkpoint inhibitor (CPI) therapy can lead to antitumor responses and prolonged survival in NSCLC, but most patients (pts) who initially benefit acquire CPI resistance with disease progression. Sitravatinib (sitra) is a receptor tyrosine kinase inhibitor that can resensitize tumors to CPI by shifting the tumor microenvironment towards a less immunosuppressive state and, combined with nivolumab (nivo), may overcome acquired CPI resistance and improve outcomes vs chemotherapy.
Methods
In the Phase 3 SAPPHIRE study, pts with advanced non-squamous (adv nsq) NSCLC (excluding EGFR, ROS1, or ALK alterations) who initially benefited from CPI with/after platinum-based chemotherapy (≥4 months [mos] on CPI without progression) with subsequent disease progression were randomized 1:1 to sitra (100 mg QD orally) plus nivo (240 mg Q2W or 480 mg Q4W IV) [sitra/nivo] or docetaxel monotherapy (doce; 75 mg/m2 Q3W IV). The primary endpoint was overall survival (OS). Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS); all by blinded independent central review, and safety.
Results
As of 20 March 2023 (median follow-up, 17.1 mos), 577 pts received sitra/nivo (n=284) or doce (n=293). Median OS was not significantly improved by sitra/nivo vs doce (12.2 vs 10.6 mos; HR 0.86 [95% CI, 0.70–1.05]; p=0.144). HR for PFS was 1.08 (95% CI, 0.89–1.32; p=0.452); median PFS for sitra/nivo vs doce was 4.4 vs 5.4 mos. ORR was 15.6% with sitra/nivo vs 17.2% with doce (p=0.597); CBR was 75.5% (sitra/nivo) vs 64.5% (doce; p=0.004). Most common (≥25%) any grade treatment-related adverse events with sitra/nivo were diarrhea (56.2% [7.5% gr ≥3]), nausea (31.3% [1.4%]), decreased appetite (28.5% [1.8%]), hypothyroidism (28.1% [0.4%]), and fatigue (26.3% [6.8%]); and diarrhea (35.5% [3.3%]), fatigue (35.5% [8.4%]), nausea (32.2% [2.6%]), decreased neutrophil count (31.9% [29.3%]), alopecia (30.8% [0.4%]), and neutropenia (26.0% [23.1%]) with doce.
Conclusions
The primary endpoint of OS was not met in pts with previously treated adv nsq NSCLC. Safety profiles for sitra/nivo and doce were consistent with prior reports for each regimen.
Clinical trial identification
NCT03906071.
Editorial acknowledgement
Medical writing support for the development of this abstract, was provided by Tamsyn Mamotte, MSc, of Ashfield MedComms, an Inizio company, and funded by Mirati Therapeutics, Inc.
Legal entity responsible for the study
Mirati Therapeutics, Inc.
Funding
Mirati Therapeutics, Inc. and Bristol Myers Squibb.
Disclosure
H. Borghaei: Financial Interests, Personal, Invited Speaker: Amgen, Pfizer, Daiichi Sankyo, Regeneron; Non-Financial Interests, Personal, Writing Engagement: Amgen, BMS, AstraZeneca; Financial Interests, Personal, Advisory Board: BMS, Lilly, Genentech, Pfizer, Merck, EMD-Serono, Boehringer Ingelheim, AstraZeneca, Novartis, Genmab, Regeneron, BioNTech, Amgen, Axiom, PharmaMar, Takeda, Mirati, Daiichi Sankyo, Guardant, Natera, Oncocyte, Beigene, iTEO, Jazz, Janssen, Da Volterra, Pum; Financial Interests, Personal, Full or part-time Employment: Fox Chase Cancer Center; Financial Interests, Personal, Stocks/Shares: Sonnetbio (Stock Options); Inspirna (formerly Rgenix, Stock Options); Nucleai (stock options); Financial Interests, Institutional, Research Grant: BMS, Lilly ; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, Mirati, BMS; Financial Interests, Personal, Other, DSMB: University of Pennsylvania: CAR T Program, Takeda, Incyte, Novartis, Springworks; Financial Interests, Personal, Other, Travel: Amgen, BMS, Merck, Lilly, EMD-Serono, Genentech, Regeneron. M.L. Johnson: Financial Interests, Institutional, Research Funding: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAtla, Black Diamond, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera Biosciences, Carisma Therapeutics, Chec; Financial Interests, Institutional, Advisory Role: AbbVie, Amgen, Arcus Biosciences, Arrivent, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Calithera Biosciences, Daiichi Sankyo, EcoR1, Genentech / Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Ideaya Biosciences, Immun. E.B. Garon: Financial Interests, Institutional, Research Grant: ABL-Bio, AstraZeneca, Bristol Myers Squibb, Dynavax Technologies, Eli Lilly, EMD Serono, Genentech, Iovance Biotherapeutics, Merck, Mirati Therapeutics, Inc., Neon, Novartis; Financial Interests, Institutional, Advisory Role: AbbVie, ABL-Bio, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Dracen Pharmaceuticals, EMD Serono, Eisai, Eli Lilly, Gilead, GSK, Ipsen, Merck, Natera, Novatis, Personalis, Regeneron, Sanofi, Shionogi, Xilo. K. He: Financial Interests, Personal, Advisory Board: Mirati Therapeutics, Inc., Perthera, Bristol Myers Squibb, Iovance Biotherapeutics, Lyell, AstraZeneca, OncoC4, Beigene. D. Planchard: Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, priME Oncology, Peer CME, Samsung, AbbVie, Janssen, GSK, Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen, AbbVie, Sanofi-aventis, GSK, Seagen, Pierre Fabre, Gilead; Financial Interests, Personal, Principal Investigator: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi- Aventis, Taiho Pharma, Novocure, Daiichi Sankyo, Janssen, AbbVie, GSK. M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, GSK, Lilly, Mirati, MSD, Merck, Novartis, Regeneron, Sanofi, Roche; Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, GSK, Lilly, Mirati, MSD, Merck, Novartis, Regeneron, Sanofi, Roche; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, Biontech, Boehringer Ingelheim, Daiichi Sankyo, Gilead, GSK, MSD, Mirati, Pfizer, Regeneron, Sanofi, Roche; Financial Interests, Personal, Other, DSMB: Daiichi Sankyo, Sanofi. S. Popat: Financial Interests, Personal, Invited Speaker: Medscape, VJ Oncology, Ariad, AstraZeneca, Roche, Boehringer Ingelheim, Celgene, Daiichi Sankyo, GSK, Takeda, Trizel, Turning Point Therapeutics, Roche, Janssen, BMS, Lilly; Financial Interests, Personal, Expert Testimony: Merck Serono, Roche ; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novartis, Amgen, Janssen, Daiichi Sankyo, AstraZeneca, Bayer, Blueprint, Guardant Health, Beigene, Takeda, Lilly, Turning Point Therapeutics, GSK, MSD, Pfizer, Sanofi, EQRx; Non-Financial Interests, Personal, Officer: European Society of Medical Oncology; Non-Financial Interests, Personal, Member of Board of Directors: Mesothelioma Applied Research Foundation; Financial Interests, Institutional, Research Grant: Guardant Health ; Non-Financial Interests, Personal, Advisory Role: International Association for the Study of Lung Cancer, ALK Positive UK, Ruth StraussFoundation, Lung Cancer Europe; Non-Financial Interests, Personal, Leadership Role: British Thoracic Oncology Group, European Thoracic Oncology Platform; Financial Interests, Personal, Other: Journal Deputy Editor, Lung Cancer: Elsevier; Sub- Investigator: Amgen, MSD, Blueprint. R.S. Herbst: Financial Interests, Personal, Other, Consulting: DynamiCure Biotechnology, eFFECTOR Therapeutics, Inc, Eli Lilly and Company, Genentech, Gilead, HiberCell, Inc., Janssen, Johnson and Johnson, Loxo Oncology, Merck and Company, Mirati Therapeutics, NextCure, Novartis, Oncocyte Corp, Oncternal Therapeutics; Financial Interests, Personal, Advisory Board: AstraZeneca, Bolt Therapeutics, Bristol-Myers Squibb, Candel Therapeutics, Cybrexa Therapeutics, EMD Serono, I-Mab Biopharma, Immune-Onc Therapeutics, Inc., Normunity, Ocean Biomedical, Inc, Revelar Biotherapeutics, Inc, Ribbon Therapeutics, Xencor, Inc; Financial Interests, Personal, Member of Board of Directors: Junshi Pharmaceuticals, AACR, Immunocore, IASLC, SITC, Southwest Oncology Group; Financial Interests, Personal, Full or part-time Employment: Yale Cancer Center; Financial Interests, Personal, Stocks/Shares: Immunocore, Checkpoint Therapeutics; Financial Interests, Institutional, Other, Research support: AstraZeneca, Eli Lilly and Company, Genentech/Roche, Merck and Company. T.A. Leal: Financial Interests, Personal, Advisory Board: AstraZeneca, Novocure, Takeda, Merck, Jazz Pharmaceuticals; Financial Interests, Institutional, Research Grant: Pfizer, Advaxis, Bayer; Financial Interests, Personal, Other, Consulting: Regeron, AstraZeneca, Eisai, Roche, Catalyst, Jazz, Amgen. D. Dumoulin: Financial Interests, Institutional, Funding: BMS; Non-Financial Interests, Personal, Principal Investigator: BMS, Roche, Mirati, MSD; Non-Financial Interests, Personal, Advisory Role: Amgen, BMS, MSD. F. de Marinis: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Roche, Bristol Myers Squibb, Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Bristol Myers Squibb, Novartis. C.H. Reynolds: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Stocks/Shares: Gilead. R.L. Shazer: Financial Interests, Personal, Full or part-time Employment: Mirati Therapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Mirati Therapeutics, Inc.. X. Yan: Financial Interests, Personal, Full or part-time Employment: Mirati Therapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Mirati Therapeutics, Inc.. R. Harrigan: Financial Interests, Personal, Full or part-time Employment: Mirati Therapeutics, Inc.. S. Peters: Financial Interests, Institutional, Invited Speaker: AiCME, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, ecancer, Eli Lilly, Foundation Medicine, GSK, Illumina, Imedex, Ipsen, Medscape, Merck Sharp and Dohme, Mirati, Novartis, PER, Peerview, Pfizer, Roche/Genentech, RTP, Sanofi, Takeda; Financial Interests, Institutional, Advisory Role: AbbVie, AiCME, Amgen, Arcus, AstraZeneca, Bayer, Beigene, BerGenBio, Biocartis, BioInvent, Blueprint Medicines, Boehringer Ingelheim, Bristol- Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, F-Star, Fishawack, Foundation Me; Financial Interests, Institutional, Member of Board of Directors: Galenica; Financial Interests, Institutional, Principal Investigator: Amgen, Arcus, AstraZeneca, Beigene, Bristol-Myers Squibb, GSK, iTeos, Merck Sharp and Dohme, Mirati, Pharma Mar, Promontory Therapeutics, Roche/Genentech, Seattle Genetics; Financial Interests, Personal, Member: ESMO, ASCO, AACR, IASLC, SSOM, SAKK, ETOP; Financial Interests, Personal, Leadership Role: Vice President Swiss Cancer League, past President ESMO, Strategic Advisory board SPCC (Paris Saclay) Chair, ETOP scientific chair. All other authors have declared no conflicts of interest.
LBA64 - Overall survival from a phase II randomised double-blind trial (PERLA) of dostarlimab (dostar) + chemotherapy (CT) vs pembrolizumab (pembro) + CT in metastatic non-squamous NSCLC
- Solange Peters (Lausanne, Switzerland)
Abstract
Background
The Phase II PERLA trial (NCT04581824) was the first global randomized, double-blind, head-to-head study of two programmed death (PD)-1 inhibitors in NSCLC. In the primary analysis, dostar + CT met its primary endpoint of equivalence, with a favorable numerical trend in overall response rate (ORR) and progression-free survival compared to pembro + CT [1]. Here we report overall survival (OS) analyses from PERLA.
Methods
Patients (pts) with metastatic NSCLC, documented PD-L1 status, absence of EGFR, ALK or other actionable genomic aberrations determined locally, ECOG 0–1, and no prior systemic treatment were randomised 1:1 to dostar 500 mg or pembro 200 mg Q3W IV up to 35 cycles, combined with CT (4 cycles pemetrexed [pem; 500 mg/m2] + carboplatin [AUC 5 mg/mL/min] or cisplatin [75 mg/m2], followed by pem up to 35 cycles) Q3W IV. The primary endpoint was ORR by blinded independent central review (BICR). OS (secondary endpoint) and duration of response (DoR) by BICR (exploratory endpoint) were determined by Kaplan-Meier method, 95% confidence intervals (CIs) by Brookmeyer-Crowley method and hazard ratio by stratified Cox proportional hazard model.
Results
At data cut-off on 07 July 2023, 121 and 122 pts in the dostar + CT and pembro + CT arms respectively, were randomised and treated. OS maturity was 55% (134/243). Median OS was 19.4 mo (95% CI 14.5, NR) in the dostar + CT arm vs 15.9 mo (95% CI 11.6, 19.3) in the pembro + CT arm (Table), after median follow-up (IQR) of 20.7 (17.3, 24.0) and 21.6 (18.3, 24.1) mo respectively, with a similar trend across PD-L1 subgroups. ORR and DoR are shown in the table. No new safety signals were reported. *Brookmeyer-Crowley method; †based on profile-likelihood confidence limits; ‡according to RECIST v1.1; §Clopper-Pearson method; ¶Mantel and Haenszel method with Sato variance estimator. CI, confidence interval; CR, complete response; mo, months; NR, not reached; PR, partial response.
Dostar+CT (N=121) Pembro+CT (N=122) OS events (death), n (%) 59 (49) 75 (61) Median OS (95% CI)*, mo 19.4 (14.5, NR) 15.9 (11.6, 19.3) Hazard Ratio (95% CI)† 0.75 (0.53,1.05) ORR by BICR‡, % (95% CI)§ CR, n (%) PR, n (%) 45 (36.4, 54.8) 4 (3) 51 (42) 39 (30.6, 48.6) 6 (5) 42 (34) Difference in ORR, % (80% CI)¶ 6.04 (−1.95, 14.02) Median DoR‡ (95% CI)*, mo 12.4 (8.3, 17.9) 14.4 (9.7, NR)
Conclusions
In this follow-up analysis, dostar + CT continues to demonstrate strong clinical efficacy with no unexpected safety signals. In addition, a numerical trend in OS favoring dostar + CT vs pembro + CT was observed. 1. Peters, S
Clinical trial identification
NCT04581824.
Editorial acknowledgement
Editorial support was provided by Claire Kelly, PhD, and Mary-Clare Cathcart, PhD, of Fishawack Indicia Ltd., part of Fishawack Health, and was funded by GSK.
Legal entity responsible for the study
GSK.
Funding
GSK.
Disclosure
S. Peters: Financial Interests, Personal, Advisory Board: AbbVie, AiCME, Amgen, Arcus, AstraZeneca, Bayer, Beigene, Biocartis, BioInvent, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, F-Star, Fishawack, Foundation Medicine, Genzyme, Gilead, GSK, Illumina, Imedex, IQVIA, Incyte, iTeos, Janssen, Medscape, Medtoday, Merck Sharp and Dohme, Merck Serono, Merrimack, Novartis, Novocure, OncologyEducation, Pharma Mar, Phosplatin Therapeutics, PER, Peerview, Pfizer, PRIME, Regeneron, RMEI, Roche/Genentech, RTP, Sanofi, Seattle Genetics, Takeda, Vaccibody; Financial Interests, Personal, Invited Speaker: AiCME, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, ecancer, Eli Lilly, Foundation Medicine, Illumina, Imedex, Medscape, Merck Sharp and Dohme, Mirati, Novartis, PER, Peerview, Pfizer, Prime, Roche/Genentech, RTP, Sanofi, Takeda; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Beigene, Bristol Myers Squibb, GSK, Merck Sharp and Dohme, Roche/Genentech. A.L.O. Ortega Granados: Financial Interests, Personal and Institutional, Full or part-time Employment: Servicio Andaluz de Salud; Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Merck Sharp Dohme. F. de Marinis: Financial Interests, Personal, Advisory Role: AstraZeneca, Roche, Novartis, Merck, BMS, MSD. G. Lo Russo: Financial Interests, Personal, Other, Consulting: Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, Amgen, Sanofi, Italfarmaco, Pfizer, GSK; Financial Interests, Personal, Other, Honoraria: Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, Amgen, Sanofi, GSK; Financial Interests, Personal, Other, Travel: Roche, BMS, MSD; Financial Interests, Personal, Advisory Role: Roche, Novartis, BMS, MSD, AstraZeneca, Sanofi, GSK; Financial Interests, Personal, Other, Principle Investigator in sponsored clinical trials: Roche, Novartis, BMS, MSD, AstraZeneca, GSK, Amgen, Sanofi. M. Schenker: Financial Interests, Personal and Institutional, Other, Clinical trial activities: GSK, BMS, MSD, Roche, AstraZeneca, Merck Serono, Astellas, Amgen, Bayer, Beigene, Clovis, Gilead, Eli Lilly, Pfizer, Novartis, Sanofi, Pharma Mar, AbbVie, Regeneron, Mylan, Samsung Pharmaceuticals, Bioven, Eisai, Five Prime, Daiichi Sankyo. E. Arriola: Financial Interests, Personal, Advisory Role: BMS, Roche, MSD, Pfizer, Lilly, AstraZeneca, Boehringer Ingelheim, Takeda ; Financial Interests, Personal, Invited Speaker: BMS, Roche, MSD, Pfizer, Lilly, AstraZeneca, Boehringer Ingelheim, Takeda ; Financial Interests, Personal and Institutional, Research Grant: Roche, Pfizer; Financial Interests, Institutional, Funding: BMS, Roche, Pfizer; Financial Interests, Personal, Ownership Interest: Trialing Health. J.M. Puig: Non-Financial Interests, Personal, Principal Investigator: CER San Juan, Centro Polivalente de Asistencia e Investigación Clinica. D.H. Lee: Financial Interests, Personal, Other, Personal fees: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, CJ Healthcare, Eli Lilly, ChongKeunDang, Janssen, Merck, MSD, Mundipharma, Novartis, Ono, Pfizer, Roche, ST Cube, AbbVie, Takeda, Menarini, BC Pharma, Yuhan ; Non-Financial Interests, Personal, Other, Non-financial: Takeda, Blueprint Medicine. M. Reck: Financial Interests, Personal, Advisory Role, Lectures and consultancy: Amgen, AstraZeneca, BeiGene, BMS, Boehringer Ingelheim, Daiichi Sankyo, GSK, Lilly, Merck, MSD, Novartis, Pfizer, Regeneron, Roche, Samsung Bioepsis, Sanofi. Z. Szijgyarto: Financial Interests, Personal, Full or part-time Employment: GSK. E. Buss: Financial Interests, Personal, Full or part-time Employment: GSK; Financial Interests, Personal, Stocks/Shares: GSK. N. Stjepanovic: Financial Interests, Personal, Full or part-time Employment: GSK. S.M. Lim: Financial Interests, Personal, Research Grant: Yuhan, Janssen, Roche; Financial Interests, Personal, Other, Consulting: AstraZeneca, Boehringer Ingelheim, Lilly, Takeda, J Ints Bio; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, GSK, Hengrui, BridgeBio Therapeutics, Oscotec, Daiichi-Sankyo.
Invited Discussant LBA63 and LBA64
- Noemi Reguart Aransay (Barcelona, Spain)
Q&A
- All Speakers (Lugano, Switzerland)
LBA65 - KRYSTAL-7: Efficacy and safety of adagrasib with pembrolizumab in patients with treatment-naïve, advanced non-small cell lung cancer (NSCLC) harboring a KRASG12C mutation
- Marina C. Garassino (Chicago, United States of America)
Abstract
Background
Adagrasib (ada) is an irreversible KRASG12C inhibitor selected for favorable properties, including long half-life (23 hrs), dose-dependent PK, and CNS penetration. Optimized noncovalent binding affinity and minimized cysteine reactivity associated with ada are hypothesized to limit off-target effects in the liver and other organ sites. Preliminary ada plus pembrolizumab (pembro) data showed a manageable safety profile and encouraging clinical activity. We report updated efficacy and safety in more patients (pts) treated with ada plus pembro in KRYSTAL-7 (NCT04613596).
Methods
In the phase 2 KRYSTAL-7 study, pts with treatment-naïve KRASG12C-mutated advanced NSCLC received concurrent ada 400 mg orally BID plus pembro 200 mg intravenously Q3W. Study objectives included efficacy (investigator-assessed objective response rate [ORR], duration of response [DOR], progression-free survival [PFS], and overall survival), and safety.
Results
As of 19 June 2023, 148 pts had received ada plus pembro (median follow-up 8.7 months). Median age was 67 years, 48% were female, 39%/61% were ECOG PS 0/1. In pts with PD-L1 ≥50% (median follow-up 10.1 months), ORR was 63% (32/51 pts), disease control rate was 84%. Median DOR was not reached (NR; 95% CI 12.6–not estimable [NE]); median PFS was NR (95% CI 8.2–NE). In all pts, treatment-related adverse events (TRAEs) of any grade (gr) occurred in 94% (139/148) of pts; 55% gr3, 9% gr4, 1% gr5. TRAEs led to both ada and pembro discontinuation in 4% of pts (6% discontinued ada alone, 11% discontinued pembro alone). No pt discontinued both drugs due to ALT/AST increase or hepatic TRAEs; 1 pt discontinued ada and 3 pts discontinued pembro due to liver transaminase elevation. Additional efficacy and safety analyses will be presented.
Conclusions
After longer follow-up, concurrent ada plus pembro continued to have encouraging preliminary efficacy in pts with PD-L1 ≥50% and a manageable safety profile. These findings support initiation of a phase 3 trial evaluating concurrent ada plus pembro vs pembro for treatment-naïve pts with KRASG12C-mutated NSCLC and PD-L1 ≥50% (NCT04613596).
Clinical trial identification
NCT04613596.
Editorial acknowledgement
KRYSTAL-7 was sponsored by Mirati Therapeutics, Inc. Medical writing support for the development of this abstract, under the direction of the authors, was provided by Victoria Eyre-Book, PhD, of Ashfield MedComms, an Inizio company, and funded by Mirati Therapeutics, Inc.
Legal entity responsible for the study
Mirati Therapeutics, Inc.
Funding
Mirati Therapeutics, Inc.
Disclosure
M.C. Garassino: Financial Interests, Personal, Invited Speaker: WebMD, WebMD Oncology/Takeda, AstraZeneca, MSD, MSD Italia, Srl, GrupoPacifico-Secretaria Tenica ICAPEM/AstraZeneca, S.O.S.S.r.l, Medscape, ecancer, Roche, Bayer, Janssen, Pfizer, Celgene, Amgen, Blueprint, Sanofi, IPSEN Bioscience, Novartis, Exelixis, Spectrum Pharmaceuticals, Merck Serono, Merck, BMS, Otsuka, Incyte, Turning Point Therapeutics, Daiichi Sankyo, AstraZeneca S.p.A, MedImmune LCC, GSK, AstraZeneca AB, Merck KGaA; Financial Interests, Personal, Expert Testimony: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD International GmbH, Bayer, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Incyte, Novartis, Pfizer, Roche, Takeda, Seattle Genetics, Mirati Therapeutics, Inc., Daiichi Sankyo, Regeneron, Merck, Blueprint, Janssen, Sanofi, AbbVie, BeiGenius; Non-Financial Interests, Personal, Principal Investigator: Pfizer, Eli Lilly, MSD, Instituto Nazionale dei Tumori, GOIRC Sant'Orsola Malpighi - Bologna (Alma Mater Studiorum Universita Bologna), Istituto dei Tumori Pascale - Napoli, Gustave-Roussy Parigi Lipi Trial, O Spedali Civili Brescia, ETOP; Non-Financial Interests, Personal, Member: AIOM, WCLC, IPOP, TUTOR, AIOT, EMA SAG; Non-Financial Interests, Personal, Leadership Role: Women for Oncology Italy, AIOT, ESMO; Financial Interests, Personal, Other: AstraZeneca, MSD, Janssen, GSK, Pfizer, Seattle Genetics, AstraZeneca UK; Non-Financial Interests, Personal, Other: ASCO, AACR, ESMO; Other, Personal, Other: Pfizer, Roche, AstraZeneca, Merck. R. Jotte: Financial Interests, Personal, Advisory Board: Mirati Therapeutics, Inc.. J. Laskin: Financial Interests, Personal, Invited Speaker: Roche Canada, Jazz Pharmaceuticals, AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer, Eli Lilly, Takeda; Financial Interests, Institutional, Research Grant: Roche Canada. F. de Marinis: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Roche, BMS, Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, BMS, Novartis. C. Aguado: Non-Financial Interests, Personal, Invited Speaker: MSD, Bristol Myers Squibb, Novartis; Non-Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Sanofi, Pierre Fabre; Non-Financial Interests, Personal, Principal Investigator: Mirati Therapeutics, Inc., MSD, AstraZeneca. F.B. Badin: Non-Financial Interests, Personal, Writing Engagement: BMS, Jazz; Other, Personal, Speaker’s Bureau: BMS, Merck, Jazz, Pfizer, Lilly, Regeneron, EMD Serono, Janssen. I. Chmielewska: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Roche, MSD, Pfizer; Financial Interests, Personal, Advisory Board: Amgen, BMS; Financial Interests, Personal, Principal Investigator: Roche, Amgen, Mirati; Financial Interests, Personal, Other, Travel: Pfizer, Takeda. M.J. Hochmair: Financial Interests, Personal, Invited Speaker: AstraZeneca, Amgen, MSD, Boehringer Ingelheim, Lilly, Takeda, Roche; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Amgen, Boehringer Ingelheim, Lilly, Takeda, Roche, MSD; Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, MSD, Boehringer Ingelheim, Lilly, Takeda, Roche. S. Lu: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Hansoh; Financial Interests, Personal, Speaker’s Bureau: AstraZenca, Roche, Hansoh; Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Hutchinson MediPharma, ZaiLab, GenomiCare, Novartis, Yuhan Corporation, Menarini, Mirati, Daiichi Sankyo, D3 Bio, Simcere, Takeda, Roche, MediPharma; Financial Interests, Institutional, Research Grant: AstraZeneca, Hutchinson, BMS, Heng Rui, BeiGene, Roche, Hansoh. E. Nadal: Financial Interests, Personal, Invited Speaker: Roche, BMS, MSD, Boehringer Ingelheim, Lilly, Pfizer, Sanofi, AstraZeneca, Takeda, Amgen, Qiagen, Janssen; Financial Interests, Personal, Advisory Board: Roche, BMS, MSD, Boehringer Ingelheim, Lilly, Janssen, Pfizer, Merck Serono, Daiichi Sankyo, AstraZeneca, Takeda, Amgen, Sanofi, Qiagen, Janssen; Financial Interests, Institutional, Funding: Roche, BMS, Merck Serono; Financial Interests, Personal, Advisory Role: Pfizer, Roche. G. Ostoros: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Roche; Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, Roche. E. Felip: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Eli Lilly, Roche, Janssen, MSD, Pfizer, Sanofi, Takeda, Medscape, Peervoice, TouchOncology, Daiichi Sankyo, Exelixis, GSK, AbbVie, Novartis, Bayer, Boehringer Ingelheim, Amgen, Mirati, Merck, AstraZeneca AB, Merck KGaA; Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BMS, Daiichi Sankyo, Eli Lilly, Roche, GSK, Janssen, Merck, Novartis, Peptomyc, Pfizer, Sanofi, Takeda, MSD; Non-Financial Interests, Personal, Member: ESMO, ETOP; Non-Financial Interests, Personal, Leadership Role: SEOM; Financial Interests, Personal, Other, Grant for oncology innovation: Merck; Financial Interests, Personal, Other: Fundacion Merck Salud. A.I. Spira: Financial Interests, Personal, Invited Speaker: CytomX Therapeutics, AstraZeneca/MedImmune, Merck, Takeda, Amgen, Janssen Oncology, Novartis, BMS, Bayer; Financial Interests, Personal, Advisory Board: Incyte, Amgen, Novartis, Mirati, Gritstone Oncology, Jazz, Takeda, Janssen, Mersana, Gritstone Bio, Daiichi Sankyo/AstraZeneca, Regeneron, Array Biopharma, AstraZeneca/Medimmune, Merck, BMS, Blueprint Medicines; Financial Interests, Personal, Stocks/Shares: Eli Lilly; Financial Interests, Institutional, Research Grant: LAM Therapeutics, Regeneron, Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharma, BMS, Loxo, Arch, Gritstone, Plexxikon, Amgen, Daiichi Sankyo, ADCT, Janssen, Mirati, Rubius, Synthekine, Mersana, Blueprint, Alkermes, Revolution Medicines. C.M. Lane: Financial Interests, Personal, Full or part-time Employment: Mirati; Financial Interests, Personal, Stocks/Shares: Mirati. J. He: Financial Interests, Personal, Full or part-time Employment: Mirati Therapeutics, Inc.. R. Chao: Financial Interests, Personal, Full or part-time Employment: Mirati Therapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Mirati Therapeutics, Inc.. P.A. Jänne: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Pfizer, Roche/Genentech, Chugai, Eli Lilly, Voronoi, Daiichi Sankyo, Biocartis, Novartis, Sanofi, Takeda, Mirati, Transcenta, Silicon, Syndax, Nuvalent, Bayer, Eisai, Allorion, Accutar Biotech, AbbVie, Monte Rosa, Scorpion, Merus, Frontier, Hongyun Biotechnology, Duality Biologics; Financial Interests, Personal, Stocks/Shares: Gatekeeper Pharmaceuticals, Allorion Therapeutics; Financial Interests, Personal, Royalties: Lab Corp; Financial Interests, Personal, Research Grant: AstraZeneca, Daiichi Sankyo, PUMA, Eli Lilly, Boehringer Ingelheim, Revolution Medicines, Takeda. All other authors have declared no conflicts of interest.
LBA66 - Afatinib versus chemotherapy for treatment-naïve non-small cell lung cancer with a sensitizing uncommon epidermal growth factor receptor mutation: A phase III study (ACHILLES/TORG1834)
- Satoru Miura (Niigata, Japan)
Abstract
Background
Methods
In this open-label phase III study, treatment-naïve patients with sensitizing uncommon
Results
A total of 109 patients were enrolled between Feb 2019 and Feb 2023. The median follow-up time was 12.5 months. The patient’s backgrounds were well-balanced. The median PFS was significantly longer with afatinib treatment than with chemotherapy (10.6 vs. 5.7 months; hazard ratio for death or disease progression, 0.422; 95% confidence interval, 0.256–0.694; p = 0.0007). The data and safety monitoring committee recommended an early study termination. The objective response was similar in both groups: 61.4% with afatinib treatment and 47.1% with chemotherapy (p = 0.2069). The rate of grade ≥3 treatment resulting in adverse events in both groups was 43.8% and 37.1%, respectively. The most common adverse events in the afatinib arm were diarrhea, rash, and paronychia. One treatment related death due to pneumonitis was observed in the afatinib arm.
Conclusions
Afatinib is superior to platinum doublet chemotherapy as an initial treatment for uncommon or compound
Clinical trial identification
jRCTs 031180175.
Legal entity responsible for the study
Thoracic Oncology Research Group (TORG).
Funding
Boehringer-Ingelheim.
Disclosure
S. Miura: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, Taiho Pharmaceutical, Ono Pharmaceutical, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Boehringer-Ingelheim Japan, Pfizer, Novartis, MSD, Kyowa Hakko Kirin, Daiichi Sankyo, Nippon Kayaku, Amgen, Merck, Takeda Pharmaceutical. H. Tanaka: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai pharmaceutical, Boehringer Ingelheim, Eli Lilly, MSD, Ono pharmaceutical, Merck, Novartis, Takeda pharmaceutical, Pfizer, DaiIchi Sankyo pharmaceutical, Taiho pharmaceutical, Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Chugai pharmaceutical, Merck, AstraZeneca, MSD, Eli Lilly, Ono pharmaceutical, Bristol Myers Squibb, Merck, Takeda pharmaceutical, Taiho pharmaceutical, Pfizer, Daiichi Sankyo pharmaceutical, AbbVie. H. Yoshioka: Financial Interests, Personal, Invited Speaker, Lecture fee: Eli Lilly Japan K.K., Takeda Pharmaceutical, Nippon Boehringer Ingelheim, Nippon Kayaku, Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board, Advisor: Delta-Fly Pharma; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca, Jannsen Pharmaceutical, MSD, Novartis Pharma, Delta-Fly Pharma, Boehringer Ingelheim. T. Kurata: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Pfizer, Bristol Myers, Takeda, Eli Lilly, Chugai, Nipponkayaku, Yansen, AstraZeneca, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: MSD, Takeda. T. Fukuhara: Financial Interests, Institutional, Research Grant: MSD, Bristol Myers Squibb, Novartis. Y. Sato: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, MSD, Ono Pharmaceutical, Novartis, Pfizer, Taiho Pharmaceutical, Nippon Kayaku, Bristol Myers Squibb, Eli Lilly, Takeda, Kyowa Kirin. Y. Shiraishi: Financial Interests, Personal, Invited Speaker: Chugai Pharma, Ono Pharmaceutical, Bristol Myers Squibb Company, AstraZeneca, Taiho Pharmaceutical; Financial Interests, Institutional, Invited Speaker: Chugai Pharma; Non-Financial Interests, Principal Investigator: Chugai Pharma. S. Teraoka: Financial Interests, Personal, Invited Speaker: AstraZeneca K.K., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd., Thermo Fisher Scientific K.K.; Financial Interests, Personal, Advisory Board: Pfizer R&D Japan G.K.. T. Kato: Financial Interests, Personal, Advisory Board, speaker, consultancy: AstraZeneca, Eli Lilly, Merck Biopharma, MSD; Financial Interests, Personal, Advisory Board, speaker: Pfizer; Financial Interests, Personal, Other, consultancy: Daiichi Sankyo, Takeda, Taiho; Financial Interests, Personal, Other, consultancy, speaker: Chugai; Financial Interests, Personal, Invited Speaker: Ono, Novartis; Financial Interests, Personal, Advisory Board: BeiGene, Glaxo; Financial Interests, Personal, Full or part-time Employment, Family member: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Chugai, MSD, Pfizer, AstraZeneca, Eli Lilly, AbbVie, Regeneron, Novartis, Amgen, Merck Biophama, Haihe Biopharma, Blueprint Medicines, Turning Point. H. Horinouchi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly, BMS/ONO, Merck Sharp & Dohme, Roche/Chugai, Novartis, Pfizer, Boehringer Ingelheim, Kyowa-Kirin, Nihon Kayaku, AbbVie, Roche/Chugai; Financial Interests, Personal, Advisory Board: AstraZeneca, Eli Lilly, BMS/ONO, Merck Sharp & Dohme, Roche/Chugai, Amgen, Nihon Kayaku; Financial Interests, Institutional, Research Grant: Roche/Chugai, Merck Sharp & Dohme, Daiichi Sankyo, ONO pharmaceutical, AstraZeneca; Financial Interests, Institutional, Invited Speaker: AbbVie. Y. Takiguchi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, AstraZeneca, Chugai Pharma, Boehringer Ingelheim, Daiichi Sankyo, Taiho Pharmaceutical, Bristol-Myers Squibb Japan, Lilly, Pfizer, Novartis, Kyowa Kirin International, MSD, Eisai, Takeda, Amgen; Financial Interests, Personal, Other, Member of Ethics Committee: Oncolys BioPharma; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Lilly, Chugai Pharma, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: MSD Oncology, AstraZeneca, AbbVie. Y. Goto: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical Co., Ltd, Nippon Boehringer Ingelheim Co., Ltd., Chugai Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., MSD K.K., AstraZeneca K.K., GSK K.K., Pfizer Japan Inc., Takeda Pharmaceutical CO., LTD., Nippon Kayaku Co.,Ltd., Novartis Japan, Bristol-Myers Squibb K.K., Kyowa Hakko Bio Co., Ltd., Eli Lilly Japan K.K.. S. Ikeda: Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai, Ono, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Ono, Bristol Myers Squibb, Taiho, Eli Lilly, Pfizer, Boehringer Ingelheim, Takeda; Financial Interests, Research Grant: AstraZeneca, Chugai. E. Ichihara: Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Takeda Pharmaceutical, MSD, Novartis, Ono pharmaceutical, BMS, Chugai pharmaceutical, Eli Lilly Japan, Janssen Pharmaceutical K.K.; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Invited Speaker: MSD, Takeda Pharmaceutical, Janssen Pharmaceutical K.K., Giliad; Non-Financial Interests, Institutional, Product Samples: Janssen Pharmaceutical K.K.. H. Okamoto: Financial Interests, Institutional, Research Grant: MSD, Taiho, Bristol Myers Squibb. All other authors have declared no conflicts of interest.
LBA67 - A phase III, randomized study of atezolizumab plus bevacizumab and chemotherapy in patients with EGFR or ALK mutated in non-small cell lung cancer (ATTLAS, KCSG-LU19-04)
- Myung-Ju Ahn (Seoul, Korea, Republic of)
Abstract
Background
In the treatment ofnon-small cell lung cancer (NSCLC) with a driver mutation, the role of anti-PD-(L)1 antibody following tyrosine kinase inhibitor (TKI) remains unclear. This randomized, open-label, multicenter, phase 3 study evaluates the efficacy of atezolizumab plus bevacizumab and chemotherapy in
Methods
We compared the clinical efficacy of atezolizumab plus bevacizumab/paclitaxel/carboplatin (ABCP arm) followed by maintenance therapy with atezolizumab plus bevacizumab with pemetrexed plus carboplatin or cisplatin (PC arm) followed by pemetrexed maintenance. The primary endpoint was progression-free survival (PFS).
Results
A total of 228 patients with activating
Conclusions
This study is the first randomized phase 3 study to demonstrate the clinical benefit of anti-PD-L1 antibody in combination with bevacizumab and chemotherapy in
Clinical trial identification
NCT03991403.
Editorial acknowledgement
This study is under consideration of simultaneous publication in Journal of Clinical Oncology and it is pre-discussed with JCO editorial board.
Legal entity responsible for the study
Myung-Ju Ahn.
Funding
Roche.
Disclosure
All authors have declared no conflicts of interest.
Invited Discussant LBA65, LBA66 and LBA67
- Fiona Blackhall (Manchester, United Kingdom)
Q&A
- All Speakers (Lugano, Switzerland)