Abstract 103TiP
Background
The 5-year progression free survival (PFS) rate of patients with metastatic, PD-L1 negative, non-small cell lung cancer (NSCLC) remains poor, ranging from approximately 2% to 10% with standard immunotherapy-based treatment regimens. Based on promising anti-tumor activity in the phase I CodeBreaK 101 study, with partial responses observed in 62% (8/13) of PD-L1 negative patients in the first-line setting, we hypothesize that sotorasib plus platinum doublet chemotherapy will demonstrate durable clinical response and improved outcomes in this population. CodeBreaK 202 (NCT05920356) is a global phase III randomized study evaluating the efficacy of sotorasib versus pembrolizumab in combination with platinum doublet chemotherapy as first-line treatment for metastatic or locally advanced, PD-L1 negative, KRAS G12C-mutated NSCLC.
Trial design
Patients will be randomized 1:1 to either sotorasib 960 mg once daily or pembrolizumab administered in combination with carboplatin and pemetrexed for 4 cycles, followed by maintenance treatment with sotorasib or pembrolizumab administered in combination with pemetrexed. Key eligibility criteria include treatment-naïve metastatic or locally advanced stage IIIB/C disease that is not amenable to definitive chemoradiation, PD-L1 <1% expression, presence of KRAS G12C mutation, non-squamous tumor histology, and absence of actionable genomic alterations such as EGFR mutations and ALK rearrangements. Patients with both treated and untreated brain metastases are eligible if clinically asymptomatic. The primary endpoint is PFS per RECIST v1.1 by blinded independent central review (BICR). Key secondary endpoints include overall survival and objective response rate. Exploratory endpoints include intra-cranial PFS per RANO-BM criteria. Approximately 750 patients are planned to be enrolled and recruitment began on November 18, 2023.
Clinical trial identification
NCT05920356.
Editorial acknowledgement
Medical writing support was provided by Tim Harrison, PharmD (Amgen Inc.).
Legal entity responsible for the study
Amgen Inc.
Funding
Amgen Inc.
Disclosure
F. Barlesi: Financial Interests, Institutional, Advisory Board: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, Mirati, MSD, Pierre Fabre, Pfizer, Sanofi Aventis, Seattle Genetics, Takeda, abbvie, ACEA, Amgen, Eisai, Ignyta; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, BMS, Merck, Pierre Fabre, F. Hoffmann-La Roche Ltd., Innate Pharma, Mirati. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, Sanofi, Takeda, Touch Oncology, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Invited Speaker, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, BeiGene, Boehringer Ingelheim GmbH, Bristol Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Non-Financial Interests, Personal, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Personal, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Personal, Member, Member of the Scientiffic Advisory Committee: CAC Hospital Universitari Parc Taulí. S. Popat: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novartis, Amgen, Janssen, Daiichi Sankyo, AstraZeneca, Bayer, BMS, Blueprint, Guardant Health, BeiGene, Takeda, Lilly, Turning Point Therapeutics, GSK, MSD, Pfizer, Sanofi, EQRx; Financial Interests, Personal, Expert Testimony: Merck Serono, Roche; Financial Interests, Personal, Invited Speaker: Medscape, VJ Oncology; Financial Interests, Personal, Other, Journal Deputy Editor, Lung Cancer: Elsevier; Financial Interests, Institutional, Other, Sub-investigator: Amgen; Financial Interests, Institutional, Invited Speaker: Ariad, AstraZeneca, Roche, Boehringer Ingelheim, Celgene, Daiichi Sankyo, GSK, Takeda, Trizel, Turning Point Therapeutics, Roche, Janssen, BMS, Lilly; Financial Interests, Institutional, Other, Sub-Investigator:MSD, Blueprint; Financial Interests, Institutional, Research Grant: Guardant Health; Non-Financial Interests, Personal, Leadership Role, Chair of Steering Committee, Unpaid: British Thoracic Oncology Group; Non-Financial Interests, Personal, Officer, Thoracic Faculty, Unpaid: European Society of Medical Oncology; Non-Financial Interests, Personal, Leadership Role, Foundation Council Member, Unpaid: European Thoracic Oncology Platform; Non-Financial Interests, Personal, Advisory Role, Mesothelioma Task-force Member, Unpaid: International Association for the Study of Lung Cancer; Non-Financial Interests, Personal, Member of Board of Directors, Unpaid: Mesothelioma Applied Research Foundation; Non-Financial Interests, Personal, Advisory Role, Honorary Clinical Advisor, Unpaid: ALK Positive UK; Non-Financial Interests, Personal, Advisory Role, Research Advisory Group Member, Unpaid: Ruth Strauss Foundation; Non-Financial Interests, Personal, Advisory Role, Scientific Advisory Board Member, Unpaid: Lung Cancer Europe. B. Solomon: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, Merck, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Roche/Genentech; Financial Interests, Personal, Advisory Board: Amgen, Roche-Genentech, Eli Lilly, Takeda, Janssen; Financial Interests, Personal, Full or part-time Employment, Employed as a consultant Medical Oncologist at Peter MacCallum Cancer Centre: Peter MacCallum Cancer Centre; Financial Interests, Personal, Member of Board of Directors: Cancer Council of Victoria, Thoracic Oncology Group of Australasia; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Institutional, Invited Speaker, Principal Investigator and Steering committee Chair: Roche/Genentech, Pfizer; Financial Interests, Institutional, Invited Speaker: Novartis. J. Wolf: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Blueprint, BMS, Boehringer Ingelheim, Daiichi Sankyo, Janssen, Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda, Nuvalent, Pierre Fabre, Merck, Mirati; Financial Interests, Personal, Invited Speaker: Bayer, Chugai; Financial Interests, Institutional, Research Grant: BMS, Janssen, Novartis, Pfizer. B.T. Li: Financial Interests, Personal, Royalties, Intellectual property rights as a book author: Karger Publishers, Shanghai Jiao Tong University Press; Financial Interests, Institutional, Other, Inventor on institutional patents at MSK (US62/685,057, US62/514,661): Memorial Sloan Kettering Cancer Center; Financial Interests, Institutional, Invited Speaker, Institutional clinical trials funding to Memorial Sloan Kettering Cancer Center: Amgen, AstraZeneca, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, Hengrui, Lilly; Non-Financial Interests, Personal, Advisory Role, Uncompensated advisor and consultant: Amgen, AstraZeneca, Boehringer Ingelheim, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, Lilly; Non-Financial Interests, Personal, Other, Academic travel support, but without compensation: MORE Health, Jiangsu Hengrui Pharmaceuticals; Non-Financial Interests, Personal, Member: American Society of Clinical Oncology, International Association for the Study of Lung Cancer. Y. Wu: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Hengrui, Merck, MSD, Pfizer, Roche, Sanofi, AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, Merck, MSD, Pfizer, Roche, Sanofi, Yunhan, Eli Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Takeda; Non-Financial Interests, Personal, Leadership Role: Chinese Thoracic Oncology Group (CTONG); Non-Financial Interests, Personal, Other, WCLC 2020 Conference Chair: IASLC; Non-Financial Interests, Personal, Leadership Role, Past President: Chinese Society of Clinical Oncology (CSCO). K.M. Kerr: Financial Interests, Personal, Advisory Board, Consultancy: AbbVie, Amgen, AstraZeneca, Bayer, Debiopharm, Diaceutics, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Roche Diagnostics/Ventana, Janssen; Financial Interests, Personal, Invited Speaker: AstraZeneca, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Roche Diagnostics/Ventana, Medscape, Prime Oncology; Financial Interests, Personal, Advisory Board: Sanofi; Non-Financial Interests, Personal, Leadership Role, Past Pathology Committee Chair: IASLC; Non-Financial Interests, Personal, Member, Lobbying and pressure group for UK - generally writing reports to lobby government.: UK Lung Cancer Consortium. H. Akamatsu: Financial Interests, Personal, Research Grant: Amgen Inc., Chugai Pharmaceutial Co. Ltd, MSD K.K.; Financial Interests, Personal, Other, Lecture honoraria or fees: Amgen Inc., AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Bristol Myers Squibb, Eli Lilly Japan K.K., MSD K.K., Nippon Kayaku Co. Ltd, Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd, Pfizer Inc., Takeda Pharmaceutical Co. Ltd, Taiho Pharmaceutical Co. Ltd; Financial Interests, Personal, Advisory Board: Amgen Inc., Janssen Pharmaceutical K.K., Sandoz, Boehringer Ingelheim; Financial Interests, Personal, Leadership Role: IASLC patient advocacy committee. D.R. Camidge: Financial Interests, Personal, Advisory Role: AbbVie, Anheart, Apollomics, AstraZeneca, Aveo, BeiGene, Bristol Myers Squibb, Coherus, Eli Lilly, Gilead, Hengrui, Immunocore, Janssen, Lianbio, Merck KGa, Mirati, Nalo Therapeutics, Newsoara, Nextcure, Prelude, Roche, Sanofi, SeaGen, Sutro, Takeda, Valence, Xencor, Daiichi Sankyo, EMD Serono, Elevation, Medtronic, Mersana, Onkure, Regeneron, Turning Point, Theseus, Xcovery, Amgen, Bio-Thera, Blueprint, Helsinn, Puma, Ribon, Genentech, Dizal; Financial Interests, Personal, Advisory Board: Imagene, Kestrel, Nuvalent; Financial Interests, Personal, Stocks/Shares: Kestrel; Financial Interests, Institutional, Principal Investigator: AbbVie, AstraZeneca, Blueprint, Dizal, Inhibrx, Karyopharm, Nuvalent, Pfizer, Phosplatin, Psioxus, Rain, Roche/Genentech, SeaGen, Takeda, Turning Point, Verastem. R. Gupta, A. Meloni, T. Dai: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. H. Borghaei: Financial Interests, Personal, Advisory Board: BMS, Genentech, Eli Lilly, Merck, EMD-Serono, AstraZeneca, Novartis, Genmab, Regeneron, Amgen, Takeda, PharmaMar, Jazz Pharma, Mirati, Daiichi Sankyo, Guardant, Natera, Oncocyte, BeiGene, iTeo, Boehringer Ingelheim, Puma, BerGenbio, Janssen; Financial Interests, Personal, Other, Training discussion: Pfizer; Financial Interests, Personal, Other, DSMB: Novartis; Financial Interests, Institutional, Other, Clinical trial support: BMS, Amgen; Financial Interests, Personal, Stocks/Shares, Options for scientific advisory role: Sonnetbio; Financial Interests, Personal, Stocks/Shares, Options for scientific advisory board: Nucleai, Inspira (Rgenix); Financial Interests, Institutional, Invited Speaker, Investigator initiated trial support: BMS, Amgen, Lilly; Financial Interests, Personal and Institutional, Invited Speaker, Chair steering committee: Mirati; Financial Interests, Personal and Institutional, Invited Speaker: Amgen, AstraZeneca; Financial Interests, Personal, Invited Speaker, Also trial support: BMS; Other, Personal, Other, DSMB: Novartis, Takeda, Incyte, Springworks.