LBA10 - Sotorasib versus docetaxel for previously treated non-small cell lung cancer with KRAS G12C mutation: CodeBreaK 200 phase III study

Background

Sotorasib, an oral, irreversible KRAS^G12C inhibitor, is approved for the treatment of pre-treated adults with KRAS G12C-mutated advanced NSCLC. Here we report the primary analysis of the phase 3 CodeBreaK 200 trial comparing sotorasib vs docetaxel in KRAS G12C-mutated NSCLC.

Methods

In this global, open-label phase 3 trial, 345 patients (pts) with KRAS G12C-mutated NSCLC who progressed after prior platinum-based chemotherapy and a checkpoint inhibitor were randomized 1:1 to oral sotorasib (960 mg daily) or intravenous docetaxel (75 mg/m² every 3 weeks). Primary endpoint was progression-free survival (PFS) assessed by blinded independent central review per RECIST 1.1. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. After study initiation and per regulatory guidance, initial planned enrollment of 660 pts was reduced, and crossover from docetaxel to sotorasib was permitted following disease progression.

Results

At a median study follow-up of 17.7 months, the study met its primary endpoint of a statistically significant improvement in PFS with sotorasib vs docetaxel (HR, 0.66 [95% CI: 0.51, 0.86], P-value, 0.002). One-year PFS was 24.8% for sotorasib vs 10.1% for docetaxel, and PFS benefit was consistent across subgroups. ORR was significantly improved for sotorasib vs docetaxel (28.1% [95% CI 21.5–35.4%] vs 13.2% [95% CI: 8.6–19.2%], respectively; P<0.001). DCR was 82.5% for sotorasib vs 60.3% for docetaxel. Overall survival was not significantly different between treatment arms, though the study was not powered for OS. Safety findings are summarized (table). Table: 000LBA10

Conclusions

In this first, randomized phase 3 trial for a KRAS^G12C inhibitor, oral sotorasib demonstrated superior PFS and ORR compared to intravenous docetaxel and had a more favorable safety profile.

Clinical trial identification

NCT04303780.

Editorial acknowledgement

Medical writing assistance was provided by Liz Leight, PhD, of Amgen Inc.

Legal entity responsible for the study

Amgen Inc.

Funding

Amgen Inc.

Disclosure

M.L. Johnson: Financial Interests, Institutional, Research Grant: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAtla, Boehringer Ingelheim, Calithera Biosciences, Checkpoint Therapeutics, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Dynavax, Lilly, Elicio Therapeutics, EMD Serono, 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, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Loxo Oncology, Lycera, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Pfizer, PMV Pharmaceuticals, RasCal 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, WindMIL, Y-mAbs Therapeutics; Financial Interests, Institutional, Advisory Role: AbbVie, Amgen, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Checkpoint Therapeutics, CytomX Therapeutics, Daiichi Sankyo, EcoR1, Editas Medicine, Eisai, EMD Serono, G1 Therapeutics; Financial Interests, Institutional: Genentech/Roche. A.J. de Langen: Financial Interests, Institutional, Research Grant: BMS, MSD, Boehringer, AstraZeneca; Non-Financial Interests, Other: Merck Serono, Roche. D.M. Waterhouse: Financial Interests, Personal, Invited Speaker, Speaker, Advisory Event, Travel: BMS; Financial Interests, Personal, Invited Speaker, Speaker, Advisory Event: AstraZeneca, EMD Serono, Merck; Financial Interests, Personal, Advisory Role, Advisory Event: AbbVie, Exelixis, Eisai, Pfizer, Mirati, Regeneron/Sanofi, Fresenius Kbi; Financial Interests, Personal, Invited Speaker, Speaker, Advisory Event, Consultant: Amgen; Financial Interests, Personal, Advisory Role, Speaker, Advisory Event: Janssen; Financial Interests, Personal, Invited Speaker, Advisory Event: Seattle Genetics; Financial Interests, Personal, Advisory Role, Advisory Event, Consultant: Jazz Pharmaceuticals; Financial Interests, Personal, Advisory Role, Speaker (pend), Advisory Event: Eli Lilly. J. Mazieres: Financial Interests, Personal, Advisory Board: Merck, Roche, AstraZeneca, MSD, BMS, Pfizer, Hengruii Therapeutics, Daiichi, Boehringer, Pierre Fabre, Amgen; Financial Interests, Institutional, Research Grant: Roche, AstraZeneca, Pierre Fabre. A.C. Dingemans: Other, Institutional, Advisory Board: Amgen, Bayer, Boehringer Ingelheim, Roche, Sanofi; Other, Institutional, Invited Speaker: AstraZeneca, Janssen, Eli Lilly, Pfizer, Takeda; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Principal Investigator, Local PI: Amgen, Daiichi, JNJ, Eli Lilly, Mirati; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Roche; Financial Interests, Institutional, Other, Steering Committee Member: Roche. G. Mountzios: Financial Interests, Personal, Other, Consulting fees: Roche Hellas, Novartis Greece, BMS Greece, MSD Greece, AstraZeneca Greece, Takeda Hellas, Janssen Greece, GSK Greece, Amgen Hellas, Sanofi Greece, Boehringer Greece; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche Hellas, Novartis Greece, BMS Greece, MSD Greece, AstraZeneca Greece, Takeda Hellas, Pierre Fabre Greece, Janssen Greece, GSK Greece, Amgen Hellas, Sanofi Greece, Boehringer Greece; Financial Interests, Personal, Other, Payment for expert testimony: Roche Hellas, Novartis Greece, BMS Greece, MSD Greece, AstraZeneca Greece, Takeda Hellas, Pierre Fabre Greece, Janssen Greece, GSK Greece, Amgen Hellas, Sanofi Greece, Boehringer Greece; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Roche Hellas, Novartis Greece, BMS Greece, MSD Greece, AstraZeneca Greece, Takeda Hellas, Pierre Fabre Greece, Janssen Greece, GSK Greece, Amgen Hellas, Sanofi Greece, Boehringer Greece; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: Roche Hellas, Novartis Greece, BMS Greece, MSD Greece, AstraZeneca Greece, Takeda Hellas, Janssen Greece, GSK Greece, Amgen Hellas, Sanofi Greece, Boehringer Greece; Financial Interests, Personal, Other, Leadership or fiduciary role in other board, society, committee or advocacy group, unpaid: European Society for Medical Oncology working groups (Educational Publication Working Group, Adolescents and Young Adults working group); Financial Interests, Institutional, Principal Investigator: Roche Hellas, Novartis Greece, BMS Greece, MSD Greece, AstraZeneca Greece, Gilead Greece, GSK Greece, Amgen Hellas, Sanofi Greece. M. Pless: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Eisei, MSD, Novartis, Pfizer, Roche, Takeda, Merck, Sanofi, Bayer, Amgen; Financial Interests, Personal, Other, Travel Grant: AstraZeneca, BMS, Boehringer Ingelheim, Roche, Takeda, Vifor; Financial Interests, Personal, Invited Speaker: Janssen, Nestle. J. Wolf: Financial Interests, Personal, Other, Personal fees: Amgen, AstraZeneca, Bayer, Blueprint, BMS, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Ignyta, Janssen, Eli Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda; Financial Interests, Institutional, Research Grant: BMS, Janssen, Novartis, Pfizer. M. Schuler: Financial Interests, Personal, Other, Honoraria: Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen-Cilag, Novartis; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Merck Serono, Novartis, Roche, Sanofi, Takeda; Financial Interests, Institutional, Funding: AstraZeneca, Bristol Myers Squibb; Financial Interests, Institutional, Other, Patents, Royalties, Other Intellectual Property - Highly sensitive method for mutation detection by PCR: Institute Patent. H. Lena: Financial Interests, Personal, Other, Personal fees: Daiichi Sankyo, AstraZeneca, Pfizer, Novartis, Amgen, MSD, Roche, BMS, Eli Lilly, Boehringer Ingelheim. F. Skoulidis: Financial Interests, Personal, Other, Consulting fees: Amgen Inc; Financial Interests, Personal, Other, lecture fees: BMS, RV Mais Promocao Eventos Ltda; Financial Interests, Personal, Other, fees for travel, food and beverage: Tango Therapeutics, AstraZeneca Pharmaceuticals, Amgen Inc; Financial Interests, Personal, Stocks/Shares, stock or stock options: BioNTech SE; Financial Interests, Personal, Stocks/Shares: Moderna Inc; Financial Interests, Institutional, Research Grant: Amgen, Mirati Therapeutics, Boehringer Ingelheim, Merck & Co, Novartis; Financial Interests, Institutional, Other, Study Chair funds: Pfizer; Financial Interests, Institutional, Research Grant, To spouse: Almmune. I. Okamoto: Financial Interests, Institutional, Research Grant: Amgen Inc, AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, MSD Oncology, Eli Lilly, Astellas Pharma, Bristol Myers Squibb, Novartis, Chugai Pharma, AbbVie; Financial Interests, Personal, Other, Personal fees: AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, MSD Oncology, Eli Lilly, Bristol Myers Squibb, Chugai Pharma, Pfizer. S. Kim: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, Takeda, Yuhan; Financial Interests, Personal, Funding, Fund for IIT: Yuhan; Financial Interests, Personal, Invited Speaker: Amgen, Boehringer Ingelheim, Janssen, Novartis, Takeda. H. Linardou: Financial Interests, Personal, Other, Consulting fees: Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, GSK, Merck, Amgen, Boehringer, Pfizer, Lilly; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, AbbVie, GSK, Amgen, Boehringer, Pfizer, Lilly; Financial Interests, Personal, Other, Payment for expert testimony: Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, GSK, Amgen, Boehringer, Pfizer, Lilly; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Roche, Novartis, BMS, MSD, AstraZeneca, GSK, Amgen, Boehringer, Pfizer; Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, GSK, Amgen, Boehringer, Pfizer, Lilly; Other, Personal, Leadership Role, W4O Core Committee - Unpaid: European Society for Medical Oncology; Other, Personal, Leadership Role, President of the Scientific Committee and Member of the Board of Directors - Unpaid: Hellenic Cooperative Oncology Group; Other, Personal, Leadership Role, Member of Board of Directors - Unpaid: Hellenic Foundation for Cancer Research, FairLife LCC; Other, Personal, Leadership Role, Legal Representative Member of Board of Directors - Unpaid: W4O-Hellas; Financial Interests, Personal and Institutional, Principal Investigator, PI in sponsored clinical trials, personal and institutional fees: Bristol Myers Squibb, Boehringer Ingelheim, Roche, Abbvie, Lilly, Novartis, AstraZeneca, Amgen, PPD, Parexel ILR, Qualitis, Health Data Specialist. S. Novello: Financial Interests, Personal, Speaker’s Bureau, Advisor/Speaker Bureau: AstraZeneca, AMG, BI, Sanofi, Novartis, Pfizer, Takeda, Roche, Eli Lilly, Janssen; Financial Interests, Personal, Advisory Role, Advisor/Speaker Bureau: AstraZeneca, AMG, BI, Sanofi, Novartis, Pfizer, Takeda, Roche, Eli Lilly, Janssen. Y. Chen: Other, Personal, Other, speaker faculty: Amgen, AstraZeneca, Bristol Myers Squibb, Guardant Health, Jazz Pharmaceutical, Pfizer, Takeda; Other, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Mirati; Financial Interests, Institutional, Principal Investigator: Amgen, AstraZeneca, Bristol Myers Squibb, EMD/Sorono, Helsinn, Ipsen, Merck. B. Solomon: Financial Interests, Institutional, Funding, Institutional funding for conduct of clinical trial: Amgen; Financial Interests, Personal, Advisory Board, Advisory Board/Honoraria: Amgen, Roche-Genentech, Novartis, Pfizer, AstraZeneca, Bristol Myers Squibb, Takeda, Eli Lilly, Merck Shape Dohme, Janssen. C. Obiozor, Y. Wang: Financial Interests, Personal, Full or part-time Employment, Employee and shareholder: Amgen. L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, Beigene, Daiichi, 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, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Other, Member: AACR, ASCO, ESMO; Financial Interests, Other, Foundation Board Member: AECC; Financial Interests, Other, President: ASEICA (Spanish Association of Cancer Research ); Financial Interests, Other, Foundation President: ONCOSUR; Financial Interests, Other, member: Small Lung Cancer Group.