1305P - Sotorasib long-term clinical outcomes in pretreated KRAS G12C-mutated advanced NSCLC: Pooled analysis from the CodeBreaK clinical trials

Background

Sotorasib is a first-in-class KRAS^G12C inhibitor that is globally approved for patients with pre-treated KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC). We present long-term outcomes for sotorasib from a pooled analysis across the CodeBreaK clinical development program.

Methods

Data were pooled from phase 1 to 3 trials of patients who received sotorasib 960 mg once daily (N=549). Trials included CodeBreaK 100 (phase 1, phase 2), CodeBreaK 101 (phase 1 subprotocol G), CodeBreaK 105 (phase 1), and CodeBreaK 200 (phase 3). Patients had KRAS G12C-mutated advanced NSCLC and disease progression after prior checkpoint inhibitor and/or platinum-based chemotherapy. Median progression-free survival (PFS), overall survival (OS), and duration of response (DOR) were evaluated. Patients who had crossed over from docetaxel in CodeBreaK 200 were excluded from the efficacy analysis.

Results

In a total of 465 patients evaluated for efficacy, median age was 65 years (range: 32–88), most had ECOG PS of 1 (66.7%), and 29.5% had a history of brain metastasis. Median number of prior lines of therapy was 2. Median follow-up was 17.9 (95% CI: 16.6, 20.1) months. Median PFS was 5.6 (95% CI: 5.2, 6.8) months and was consistent among patients with (4.9 [95% CI: 4.1, 6.9] months) or without (5.7 [95% CI: 5.4, 7.8] months) a history of brain metastasis. Median OS was 11.6 (95% CI: 10.0, 14.0) months. OS benefit was seen in patients with (10.2 [95% CI: 8.2, 12.7] months) and without (12.9 [95% CI: 10.0, 17.2] months) a history of brain metastasis. Kaplan-Meier estimated OS at 18 months was 37.0% (95% CI: 31.9, 42.2). Objective response rate (ORR) by central review was 33.6% (95% CI: 29.3, 38.1), and median DOR was 10.6 (95% CI: 8.3, 13.8) months. Grade ≥ 3 treatment-related adverse events (TRAEs) were reported in 147 (26.8%) patients, with the most common being diarrhea (7%), elevated ALT (7%), and elevated AST (5%). Additional efficacy subgroup analyses will be reported.

Conclusions

In the largest pooled efficacy analysis of a KRAS^G12C inhibitor, sotorasib showed clinical benefit across PFS and OS analyses, including in patients with a history of brain metastases. TRAEs were consistent with the known safety profile of sotorasib.

Clinical trial identification

NCT03600883, NCT04185883, NCT04380753, NCT04303780.

Editorial acknowledgement

Medical writing support was provided by Tim Harrison, PharmD (employee of Amgen Inc.) and Advait Joshi, PhD (Cactus Life Sciences - part of Cactus Communications).

Legal entity responsible for the study

Amgen Inc.

Funding

Amgen Inc.

Disclosure

F. Skoulidis: Financial Interests, Personal, Stocks or ownership: BioNTech; Moderna Therapeutics; Financial Interests, Personal, Other, Honoraria: ESMO; McGill Universite de Montreal; Moving Innovation and Technology; Physicans' Education Resource; RV Mais; Financial Interests, Personal, Advisory Role: Amgen; BeiGene; Calithera Biosciences; Guardant Health; Intellisphere; Medscape; Navire; Novartis; Tango Therapeutics; Financial Interests, Institutional, Research Funding: AIMM Therapeutics; Amgen; Boehringer Ingelheim; Merck; Mirati Therapeutics; 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, Coordinating PI, Institutional clinical trials funding to Memorial Sloan Kettering Cancer Center: Amgen, AstraZeneca, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, Hengrui, Lilly; Financial Interests, Institutional, Funding, Institutional clinical trial funding to Memorial Sloan Kettering Cancer Center: Revolution Medicines; Non-Financial Interests, Advisory Role, Uncompensated advisor and consultant: Amgen, AstraZeneca, Boehringer Ingelheim, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, Lilly; Non-Financial Interests, Other, Academic travel support, but without compensation: MORE Health, Jiangsu Hengrui Pharmaceuticals; Non-Financial Interests, Member: American Society of Clinical Oncology, International Association for the Study of Lung Cancer. M.J. Hochmair: Financial Interests, Personal, Advisory Board: Roche, BMS, MSD, Lilly, Amgen, Takeda; Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, BMS, MSD, Lilly, Amgen, Takeda; Financial Interests, Personal, Speaker’s Bureau: Roche, BMS, MSD, Lilly, Amgen, Takeda. R. Govindan: Financial Interests, Personal, Advisory Role: Merck, Jacobio, Precisca. M. Vincent: Financial Interests, Personal, Invited Speaker, Invited speaker on ctDNA in lung cancer: AstraZeneca; Financial Interests, Institutional, Research Grant, Investigator initiated trial on lung cancer in Canada: AstraZeneca; Non-Financial Interests, Principal Investigator, PI of a clinical trial on lung cancer in Canada: AstraZeneca. A.J. Van Der Wekken: Financial Interests, Institutional, Research Funding: AstraZeneca, Boehringer-Ingelheim, Pfizer, Roche, Takeda; Financial Interests, Institutional, Advisory Board: AstraZeneca, Boehringer-Ingelheim, Janssen, Lilly, Novartis, Pfizer, Roche, Takeda; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer Ingelheim-Janssen, Ingelheim, Lilly, Novartis, Pfizer, Roche, Takeda. N. Reguart Aransay: Financial Interests, Personal, Advisory Board: Roche, MSD, Takeda, Bayer, Boehringer, Pfizer, Novartis, Sanofi, Janssen, AstraZeneca, Amgen, Novartis, Merck, Janssen, AbbVie; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, BMS, Amgen, Novartis, Sanofi, Merck; Non-Financial Interests, Principal Investigator, PI of Investigator Initiated Trial (PEERS) sponsored by MSD: MSD. K.J. O'Byrne: Financial Interests, Personal, Other, Advisor/consultant on project development by the company: TriStar; Financial Interests, Personal, Other, Invited speaker; advisory board: BMS; Financial Interests, Personal, Other, Advisory board; invited speaker: AstraZeneca, MSD, Janssen; Financial Interests, Personal, Other, advisory board; invited speaker: Roche; Financial Interests, Personal, Advisory Board: Boehringer-Ingelheim; Financial Interests, Personal, Other, Advisory board: Pfizer; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Advisory Board, Advice on development of Lasertinib: Yuhan; Financial Interests, Personal, Other, advisory board and invited speaker: Takeda, Seagen; Financial Interests, Personal, Advisory Board, Advice re cabozantinib: Ipsen; Financial Interests, Personal, Advisory Board, Advice of drug development program, advisory board work and invited speaker: BeiGene; Financial Interests, Personal, Invited Speaker, Topic - Tepotinib: Merck; Financial Interests, Personal, Other, Sponsorship for travel, accommodation and registration for ESMO Congress, Paris, 2022: Bayer; Financial Interests, Personal, Other, Sponsorship to ESMO annual congress 2023 - flights, registration and accommodation: Sanofi; Financial Interests, Personal, Stocks/Shares, 5% non-dilutable shares in a start-up Pharma company: RepLuca Pharmaceuticals Pty Ltd.; Financial Interests, Personal, Stocks/Shares, Start-up diagnostics focused on genomics: DGC diagnostics; Financial Interests, Personal, Other, Co-founder, board member and share holder (15%) in the Pharma and biotech company: Carpe Vitae Pharmaceuticals Pty Ltd.; Financial Interests, Personal, Steering Committee Member, Steering committee member 2 trials- CA-209-227- CA-001-050: BMS; Financial Interests, Personal, Steering Committee Member, Steering Committee member LUX-Lung program: Boehringer-Ingelheim; Non-Financial Interests, Other, Chair an education session: foundation medicine. N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi, gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS, Leo Pharma; Financial Interests, Institutional, Research Grant: MSD; Other, Family member is an employee: AstraZeneca. F. Griesinger: Financial Interests, Personal and Institutional, Other, Scientific support: Astra, Boehringer, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Siemens, Amgen, GSK, Daiichi Sankyo, Gilead; Financial Interests, Personal and Institutional, Other, Oral presentations with honoraria: Astra, Boehringer, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Ariad, AbbVie, Siemens, Tesaro/GSK, Amgen, Sanofi, Daiichi Sankyo, BeiGene, Gilead, Merck; Non-Financial Interests, Personal and Institutional, Advisory Board: ASTRA, Boehringer, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Ariad, AbbVie, Tesaro/GSK, Siemens, Tesaro, Amgen, Sanofi, Daiichi Sankyo, BeiGene, Gilead, Merck. M. Nishio: Financial Interests, Personal, Invited Speaker, lectures fee: Ono Pharmaceuticals; Financial Interests, Personal, Invited Speaker, lectures: Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb, Daiichi Sankyo, AstraZeneca, MSD, AbbVie, Takeda, Pfizer, Boehringer Ingelheim, Novartis, Nippon Kayaku, Merck, Janssen; Financial Interests, Personal, Invited Speaker, lectures,: Lilly. S. Häfliger: Financial Interests, Institutional, Advisory Role: AstraZeneca; Bayer; Lilly; Novartis; Roche; Takeda; Financial Interests, Personal, Other, Travel support: Amgen. C. Lindsay: Financial Interests, Personal, Invited Speaker, Advisory role: Amgen; Financial Interests, Personal, Invited Speaker, Educational Presentation/Workshop: Amgen; Financial Interests, Personal, Advisory Board: Qiagen; Financial Interests, Institutional, Coordinating PI, CI for a phase III clinical trial: Mirati Therapeutics, Amgen; Financial Interests, Institutional, Coordinating PI, CI for a phase I-II clinical trial: BI, Revolution Medicines; Financial Interests, Institutional, Coordinating PI, CI for a phase II clinical trial: Roche; Financial Interests, Institutional, Local PI, PI for a phase II clinical trial: Apollomics; Financial Interests, Institutional, Research Grant, Research funding which includes use of their medical products: Revolution Medicines; Non-Financial Interests, Personal, Other, Travel funding for poster presentation: Boehringer Ingelheim; Other, Review paper co-oordinated by Amgen. Initially drafted by other writers, with contributions from co-authors.: Amgen. N. Reinmuth: Financial Interests, Personal, Invited Speaker, including Ad-Boards: AstraZeneca; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, F. Hoffmann-La Roche, Lilly, Pfizer, Takeda, Merck, GSK; Financial Interests, Personal, Invited Speaker, including Advisory Boards: Bristol Myers Squibb, Boehringer-Ingelheim, MSD; Financial Interests, Institutional, Invited Speaker: Sanofi. A. Paulus: Financial Interests, Advisory Board, Honoraria: Roche. C. Obiozor, C. Nduka, Y. Wang: Financial Interests, Personal, Full or part-time Employment: Amgen Inc.; Financial Interests, Personal, Stocks/Shares: Amgen Inc. A.J. De Langen: Financial Interests, Personal, Research Grant: BMS, MSD, Boehringer Ingelheim, AstraZeneca; Non-Financial Interests, Personal, Other: Merck Serono, Roche. All other authors have declared no conflicts of interest.