Durvalumab (D) +/- tremelimumab (T) + chemotherapy (CT) in 1L metastatic (m) NSCLC: Overall survival (OS) update from POSEIDON after median follow-up (mFU) of approximately 4 years (y)

ABSTRACT

Background: In the Phase 3 POSEIDON study, 1L T+D+CT demonstrated statistically significant improvements in PFS and OS (OS HR 0.77;95% CI 0.65-0.92;p=0.0030;mFU 34.9 mo in censored pts) vs CT alone in pts with mNSCLC. D+CT showed a statistically significant improvement in PFS and a positive trend for OS improvement vs CT that did not reach significance (OS HR 0.86;95% CI 0.72-1.02;p=0.0758). Here we report an updated exploratory analysis of OS, and histology and mutational status subgroups, after a mFU of ~4 y. Method(s) Pts with EGFR/ALK wild-type mNSCLC were randomised 111 to 1L D (until progression) +/- limited-course T (up to 5 doses) + platinum-based CT (up to 4 cycles);or CT (up to 6 cycles). Alpha-controlled endpoints were PFS and OS for D+CT vs CT and T+D+CT vs CT. Pt tumours were molecularly characterised via sequencing of tissue and/or ctDNA samples. Result(s) At an updated data cutoff (DCO) of 11 Mar 2022 (mFU 46.5 mo in censored pts), T+D+CT continued to show OS benefit vs CT (HR 0.75;95% CI 0.63-0.88) with an estimated 25.0% of pts alive at 3 y vs 13.6% (Table). D+CT continued to numerically improve OS vs CT (HR 0.84;95% CI 0.71-0.99;3 y OS 20.7%). Consistent with results at the earlier DCO, OS benefit appeared more pronounced with T+D+CT vs CT in pts with non-squamous (than squamous;data will be presented) histology. A trend for OS benefit with T+D+CT vs CT continued to be observed in non-squamous subgroups with mutations (m) in STK11 (Table), KEAP1 or KRAS (data will be presented). No new safety signals were identified based on collection of serious AEs during long-term FU. [Formula presented] Conclusion(s) The results of this exploratory analysis from POSEIDON, after mFU of ~4 y, demonstrate the durable long-term OS benefit of adding a limited course of T to D and 4 cycles of CT. These data support the use of this regimen as a 1L treatment option for pts with mNSCLC, including harder-to-treat mutational subgroups such as STK11m, KEAP1m or KRASm. Clinical trial identification NCT03164616 (release date 23 May 2017). Editorial acknowledgement Medical writing support for the development of this , under the direction of the authors, was provided by James Holland, PhD, of Ashfield MedComms (Macclesfield, UK), an Inizio company, and was funded by AstraZeneca. Legal entity responsible for the study AstraZeneca PLC. Funding(s) AstraZeneca. Disclosure B.C. Cho Financial Interests, Personal, Advisory Board KANAPH Therapeutic Inc, Brigebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc;Financial Interests, Personal, Member of the Board of Directors Interpark Bio Convergence Corp., J INTS BIO;Financial Interests, Personal, Stocks/Shares TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp, J INTS BIO;Financial Interests, Personal, Royalties Champions Oncology;Financial Interests, Personal, Research Grant Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GIInnovation, Eli Lilly, Blueprint medicines, Interpark Bio Convergence Corp;Financial Interests, Personal, Advisory Role, Consulting Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint medicines;Financial Interests, Personal, Other DAAN Biotherapeutics. 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E.B. Garon Financial Interests, Personal, Advisory Board ABL Bio, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Dracen Pharmaceuticals, Eisai, Eli Lilly, EMD Serono, Gilead, GSK, Merck, Natera, Novartis, Personalis, Regeneron, Sanofi, Shionogi, Xilio Therapeutics;Financial Interests, Personal, Research Grant ABL Bio, AstraZeneca, Bristol Myers Squibb, Dynavax Technologies, EMD Serono, Genentech, Iovance Biotherapeutics, Eli Lilly, Merck, Mirati Therapeutics, Neon Therapeutics, Novartis. T.S.K. Mok Financial Interests, Personal, Invited Speaker ACEA Pharma, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., Ltd., AstraZeneca (before 1/1/19), BeiGene, BI, BMS, Daiichi Sankyo, Daz Group, Fishawack Facilitate Ltd., InMed Medical Communication, Janssen Pharmaceutica NV, Jiahui Holdings Co. Limi, Novartis, OrigiMed Co. Ltd., P. 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All other authors have declared no conflicts of interest. Copyright © 2022