1441P - Atezolizumab and bevacizumab (atezo + bev) ± radiotherapy (RT) vs docetaxel (doc) in checkpoint inhibitor (CPI)–experienced metastatic NSCLC (mNSCLC): Results from the phase Ib/II MORPHEUS-lung study

Background

The MORPHEUS platform was designed to accelerate development of novel cancer immunotherapy combinations across tumour types. The adaptive design of these global, open-label, randomised, phase Ib/II studies allows a single control arm to be compared with multiple experimental arms and provides the flexibility to open new arms or close existing arms. We report interim analysis results from the MORPHEUS-Lung study in CPI-experienced patients (pts) with mNSCLC.

Methods

Cohort 2 (C2) of MORPHEUS-Lung is enrolling pts with EGFR/ALK WT mNSCLC that has progressed on prior platinum and a CPI (anti–PD-L1/PD-1) given concurrently or sequentially. The primary endpoints are investigator-assessed ORR (RECIST v1.1) and safety. Secondary endpoints include PFS and OS. Biomarkers are also being explored. C2 pts with non-squamous mNSCLC randomised to the atezo + bev, atezo + bev + RT or doc (control) arms were included in the analysis. Data from the atezo + bev + RT arm will be presented at the meeting along with updated data for the atezo + bev and doc arms.

Results

At data cutoff (24 Aug 2022), the efficacy and safety populations included 72 pts (atezo + bev, n=40; doc, n=32). The median age was 63 y, 72% of pts (n=52) were male and 81% (n=58) had PD-L1+ NSCLC per local testing. Confirmed ORR was 18% (n=7) and 16% (n=5) in the atezo + bev and doc arms, respectively (Table); 1 pt (3%) had a complete response (atezo + bev). Gr 3-5 AEs occurred in 40% (n=16) and 59% (n=19) of pts in the respective arms (Table). Tx-related Gr 4/5 AEs only occurred in the doc arm.

Conclusions

MORPHEUS-Lung interim analysis results suggest that atezo + bev is a potential tx option for CPI-experienced pts with mNSCLC. No new safety signals were identified, and AEs were consistent with the known safety profiles of the individual agents. Atezo + bev was tolerable, with fewer Gr 3-5 AEs and tx withdrawals than with doc. Table: 1441P

NE, not estimable. ^aPer RECIST 1.1. ^bMedian survival follow-up: atezo + bev, 8.5 mo; doc, 7.2 mo. ^cGrade 5 pneumonia considered by the investigator to be tx related.

Clinical trial identification

NCT03337698.

Editorial acknowledgement

Medical writing support for this abstract, furnished by Kia C. E. Walcott, PhD, of Health Interactions, Inc., was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Legal entity responsible for the study

F. Hoffmann-La Roche, Ltd.

Funding

F. Hoffmann-La Roche, Ltd.

Disclosure

F. Ghiringhelli: Financial Interests, Personal, Other, Honoraria: Roche, MSD, Serono; Financial Interests, Institutional, Research Funding: AstraZeneca, MedImmune , Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Amgen, Roche, Genentech. 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, Local PI, 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, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Member, Member of the Scientific Advisory Committee: CAC Hospital Universitari Parc Taulí. A. Zer: Financial Interests, Personal, Invited Speaker: Roche, BMS, MSD, Takeda, Pfizer, Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca, Steba, Oncohost; Financial Interests, Personal, Stocks/Shares: Nixio; Financial Interests, Institutional, Research Grant: BMS. L. Greillier: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, MSD, Novartis, Sanofi, Takeda, Roche; Financial Interests, Personal, Invited Speaker: Lilly, Pfizer; Financial Interests, Institutional, Local PI: AstraZeneca, AbbVie, BMS, MSD, Novartis, Takeda, Pfizer, PharmaMar; Financial Interests, Institutional, Coordinating PI: Sanofi; Financial Interests, Personal, Local PI: Roche. A. Greystoke: Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, Boehringer Ingelheim, Takeda, Roche, Novartis; Financial Interests, Personal, Invited Speaker: Merck, MSD, Pfizer, Janssen; Financial Interests, Institutional, Local PI: MSD; Financial Interests, Institutional, Coordinating PI: Pfizer, AstraZeneca, Novartis, Achilles; Non-Financial Interests, Advisory Role: National Institue for Health and Clinical Excellence; Other, Clinical Lead for Cancer (paid position): North East England and Yorkshire Genomic Laboratory Hub. N. Al-Sakaff: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd. H. Helms: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. J.P. Pintoffl: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. S. Rahalkar: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. B.C. Cho: Financial Interests, Personal, Other, Consulting role: Abion, BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus Therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Janssen; Financial Interests, Personal, Advisory Board: Kanaph Therapeutic Inc, BridgeBio Therapeutics, Cyrus Therapeutics, Guardant Health, Oscotec Inc; Financial Interests, Personal, Other, Advisory role: Medpacto, Blueprint Medicines, RandBio, Hanmi; Financial Interests, Personal, Member of 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, Crown Bioscience, Imagen; Financial Interests, Institutional, Research Grant: MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Oncology, CJ Bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine., Janssen, Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, BridgeBio Therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph Therapeutics, Therapex, JINTSbio, Hanmi, CHA Bundang Medical Center; Other, Founder: Daan BioTherapeutics. All other authors have declared no conflicts of interest.