Abstract 634P
Background
IMpower133 (Ph III; NCT02763579) showed that atezo + carboplatin and etoposide (A+CE) significantly improved survival outcomes vs placebo + CE (P+CE) in pts with ES-SCLC. Previously identified biomarkers (eg PD-L1, bTMB) did not appear predictive of A+CE benefit. Associations between gene expression and survival have been reported (Nabet 2024; Liu 2023) but not between common genomic alterations and outcomes. Additionally, IMbrella A (Ph III single-arm IMpower133 extension; NCT03148418) provided the first report of 5-y OS for first-line cancer immunotherapy in ES-SCLC (estimated A+CE OS rate of 12%). Here, we report the association of WES genomic alterations with OS in IMpower133, plus IMbrella A updated results.
Methods
WES was done on IMpower133 baseline tumour samples and germline DNA from whole blood. Alterations were identified in genes shown to be recurrently mutated in SCLC (George 2015). Pts were classified as altered or wild type for each gene; OS was assessed when subgroup prevalence was ≥10%. Eligible pts from IMpower133 could enrol in IMbrella A if receiving atezo or in survival follow-up after atezo when IMpower133 closed. OS and safety were assessed.
Results
In the IMpower133 biomarker-evaluable population (BEP; n=190), WES results for recurrent SCLC mutations were similar to those of George et al. Analysed subgroups had OS HRs for A+CE vs P+CE similar to the BEP, where A+CE was associated with longer OS than P+CE. 18 out of 26 eligible pts from IMpower133 rolled over to IMbrella A. At clinical cutoff (24 May 2024), minimum follow-up for pts in the A+CE arm was 83.8 mo. The A+CE 6-y estimated OS rate was 10.8% (95% CI: 5.8, 15.8). In IMbrella A, serious AEs occurred in 28% of pts and AEs of special interest in 22%. 10 pts were alive and 4 were ongoing treatment. IMbrella A pts with WES data (n=10) showed a profile similar to the IMpower133 BEP.
Conclusions
Overall, genomic subgroups showed results similar to the BEP. While limited by small numbers and lack of long-term data for P+CE, IMbrella A exploratory OS provides information on long-term outcomes with first-line cancer immunotherapy in ES-SCLC.
Clinical trial identification
NCT02763579; NCT03148418.
Editorial acknowledgement
Medical writing assistance for this abstract was provided by Bena Lim, PhD, CMPP, of Nucleus Global, an Inizio Company.
Legal entity responsible for the study
F. Hoffmann-La Roche, Ltd.
Funding
F. Hoffmann-La Roche, Ltd.
Disclosure
S.C. Kao: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, MSD, BMS, Roche, Amgen, Beigene, Boeringher, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: MSD, BMS, Roche, AstraZeneca, Pfizer, Takeda, Beigene, Daiichi Sankyo; Financial Interests, Institutional, Other, Research grant: AstraZeneca; Non-Financial Interests, Personal, Principal Investigator: Nuvalent, AstraZeneca, Roche. M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, BMS, Boehringer-Ingelheim, Lilly, MSD, Merck, Novartis, Regeneron, Roche, Sanofi, GSK, Pfizer; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, BioNTech, Boehringer-Ingelheim, Daiichi Sankyo, Gilead, MSD, Mirati, Pfizer, Regeneron, Roche, Sanofi, GSK, Lilly; Financial Interests, Personal, Other, Member of DMSB: Daiichi Sankyo; Financial Interests, Personal, Coordinating PI: AstraZeneca; Financial Interests, Institutional, Steering Committee Member: Amgen, Boehringer-Ingelheim, Beigene, Daiichi Sankyo, GSK, BMS, Lilly, MSD, Regeneron, Roche; Financial Interests, Institutional, Local PI: Pfizer Seagen. S.V. Liu: Financial Interests, Personal, Advisory Board, Consultant: AstraZeneca, Daiichi Sankyo, Elevation Oncology, Genentech / Roche, Janssen, Jazz Pharmaceuticals, Merck, Novartis, Regeneron, Sanofi; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Catalyst, RAPT Therapeutics, Gilead, Guardant Health, Merus, Takeda, Revolution Medicines, Amgen, AbbVie, Boehringer Ingelheim, Mirati, Pfizer; Financial Interests, Personal, Invited Speaker: OSE Immunotherapeutics; Financial Interests, Institutional, Local PI: Alkermes, Elevation Oncology, Gilead, Merck, Merus, Nuvalent, RAPT, Turning Point Therapeutics, AbbVie, AstraZeneca, Puma, Ellipses; Financial Interests, Institutional, Steering Committee Member: Genentech; Financial Interests, Institutional, Coordinating PI: OSE Immunotherapeutics; Non-Financial Interests, Personal, Member: ASCO, IASLC. R. Dziadziuszko: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Pfizer, Novartis, Takeda, MSD, Bristol Myers-Squibb, GSK; Financial Interests, Personal and Institutional, Coordinating PI: Roche, AstraZeneca; Financial Interests, Personal and Institutional, Local PI: MSD, Amgen, Celon Pharma, Pfizer, Novartis, Brsitol Myers-Squibb, Eli Lilly, Loxo, Ryvu Therapeutics, Boehringer Ingelheim; Financial Interests, Personal and Institutional, Other, Subinvestigator and ad hoc Consultant: PDC* line Pharma; Financial Interests, Personal, Local PI: OSE Immunotherapeutics; Non-Financial Interests, Institutional, Product Samples: Pfizer. M.J. Hochmair: Financial Interests, Personal, Advisory Board: Roche, MSD, Boehringer Ingelheim, BMS, Takeda, Lilly. R. Bernabe Caro: Financial Interests, Personal, Advisory Board: Roche, Bristol; Financial Interests, Personal, Invited Speaker: AstraZeneca, Msd, Lilly, Sanofi, Janssen. D.M. Kowalski: Non-Financial Interests, Personal, Advisory Role: BMS, MSD, Roche, Pfizer, AstraZeneca, MEDISON, Johnson&Johnson, TAKEDA. Z.G. Andric: Financial Interests, Personal, Invited Speaker: MSD, Roche, AstraZeneca, Novartis, Merck-D. M. Oancea: Financial Interests, Personal, Full or part-time Employment: Hoffmann la Roche; Financial Interests, Personal, Stocks/Shares: Hoffmann la Roche. M. Kaul: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Roche. H. Li: Financial Interests, Institutional, Full or part-time Employment, Roche, Product Development China is a branch office of Roche Product development in China: Roche, Product Development China; Financial Interests, Personal, Stocks/Shares, I own Roche shares through Roche employee's stockt program: Roche. M.C. Lee: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Roche. B.Y. Nabet: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Roche. S. Sugawara: Financial Interests, Personal, Other, Lecture Fee: Amgen, AstraZeneca, Bristol Myers Squibb, Chugai Pharma, Eisai, Kyowa Kirin, Lilly, Merck, MSD K.K., Nippon Boehringer Ingelheim, Nippon Kayaku, Novartis, Ono Pharmaceutical, Pfizer, Sysmex, Taiho Pharmaceutical, Takeda, Thermo Fisher Scientific; Financial Interests, Institutional, Local PI: A2 Healthcare, AbbVie, Accerise, Amgen, AnHeart, AstraZeneca, Bristol Myers Squibb, Chugai Pharma, Daiichi Snakyo, EPS Corporation, MSD K.K., Nippon Boehringer Ingelheim, Ono Pharmaceutical, Parexel International, PPD-SNBL, Syneos Health, Taiho Pharmaceut. All other authors have declared no conflicts of interest.