Abstract 147P
Background
Repotrectinib demonstrated durable clinical activity among patients with ROS1 fusion-positive (ROS1+) locally advanced or metastatic NSCLC in the TRIDENT-1 non-randomized phase I/II clinical trial. However, no head-to-head evidence is available comparing repotrectinib against other approved ROS1 tyrosine kinase inhibitors (TKIs). The objective was to indirectly compare progression free survival (PFS) and objective response rate (ORR) between repotrectinib and entrectinib in patients with TKI-naïve ROS1+ locally advanced or metastatic NSCLC.
Methods
Using evidence from a systematic literature review, unanchored matching adjusted indirect comparisons (MAIC) were used to estimate population-adjusted hazard ratios (HR) for PFS and odds ratios (OR) for ORR, between repotrectinib and entrectinib. TKI-naïve cohorts from registrational trials for repotrectinib (individual patient-level data [IPD]) and entrectinib (aggregate-level data and digitized Kaplan-Meier curves) formed the evidence base. The MAIC adjusted for imbalances in pre-specified baseline prognostic and effect modifying factors (age, sex, race, smoking, performance status, brain metastasis, prior lines of therapy). Weighted Cox (for PFS) and logistic (for ORR) regression models were fit. Supplementary analyses (SA) explored the impact of missing data and modeling assumptions on effect estimates.
Results
After MAIC weighting, patient characteristics were balanced between TRIDENT-1 (repotrectinib; n=71) and ALKA-372-001, STARTRK-1&-2 (entrectinib; n=168). The population-adjusted PFS HR favoured repotrectinib over entrectinib (0.52; 95% confidence interval [CI]: 0.31-0.87); SAs were consistent with the main findings (SA HR range, 0.35 to 0.53). The adjusted ORR OR numerically favoured repotrectinib (1.53; 95% CI: 0.64-3.67), though the 95% CI included the null value; SAs were consistent (SA OR range, 1.08 to 1.84).
Conclusions
Estimates from this MAIC suggest that repotrectinib may be associated with about half the risk of progression or death compared with entrectinib in TKI-naïve patients with ROS1+ NSCLC. Comparisons with other ROS1 TKIs, and of other endpoints (e.g., safety) are underway.
Legal entity responsible for the study
Bristol Myers Squibb.
Funding
Bristol Myers Squibb.
Disclosure
J. Wolf: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Blueprint, BMS, Boehringer Ingelheim, Daiichi Sankyo, Janssen, Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda, Nuvalent, Pierre Fabre, Merck, Mirati; Financial Interests, Personal, Invited Speaker: Bayer, Chugai; Financial Interests, Institutional, Research Grant: BMS, Janssen, Novartis, Pfizer. S. Goring: Financial Interests, Institutional, Other, I work as an independent contractor for Broadstreet HEOR, which is a research organization that has been contracted by Bristol Myers Squibb and other pharmaceutical companies.: Broadstreet HEOR; Financial Interests, Institutional, Other, I work as an independent contractor for Precision Xtract, which is a research organization that does research via contracts with pharmaceutical companies.: Precision Xtract; Financial Interests, Institutional, Other, I work as an independent contractor for Canadian Agency for Drugs and Technologies in Health, conducting rapid reviews.: Canadian Agency for Drugs and Technologies in Health; Financial Interests, Institutional, Other, I have received honoraria from Professional Society for Health Economics and Outcomes Research (ISPOR) for teaching a short course in network meta-analysis methods.: Professional Society for Health Economics and Outcomes Research (ISPOR). A. Lee: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. 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, Medpacto, Blueprint medicines, RandBio, Hanmi, GC Cell, Gilead, Ridgeline Discovery GmbH; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc, J INTS Bio, Therapex Co., Ltd, Gilead, Amgen, AstraZeneca, Regeneron, Seagen, Samsung Bioepis; Financial Interests, Personal, Member of Board of Directors: Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Full or part-time Employment: Yonsei University Health System; 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, PearlRiver Bio GmbH, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: CHA Bundang Medical Center, MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, Gradiant Bioconvergence, Therapex, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, 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, JINTSbio, Hanmi, Daewoong Pharmaceutical Co., Ltd., Vertical Bio AG, Korea Institute of Oriental Medicine, National Research Foundation of Korea, KHIDI; Other, Personal, Other, Founder: DAAN Biotherapeutics; Other, Personal, : ASCO. A. Drilon: Financial Interests, Personal, Advisory Board: 14ner/Elevation Oncology, AbbVie, Amgen, ArcherDX, AstraZeneca, BeiGene, BerGenBio, Blueprint Medicines, EcoR1, Exelixis, Helsinn, Hengrui Therapeutics, Ignyta/Genentech/Roche, Janssen, Liberum, Loxo/Bayer/Lilly, Melendi, Monopteros, Monte Rosa, Novartis, Pfizer, Remedica Ltd., TP Therapeutics, Takeda/Ariad/Millennium, Tyra Biosciences, Verastem Oncology; Financial Interests, Personal, Other, CME: AiCME, Clinical Care Options, MJH Life Sciences, Med Learning, Medscape, Medscape, Onclive, Paradigm Medical Communications, PeerView Institute, PeerVoice, Physicians Education Resources, Targeted Oncology, WebMD; Financial Interests, Personal, Other, Consulting: Applied Pharmaceutical Science, Inc, EPG Health, Entos, Harborside Nexus, Merus, Nuvalent, Ology, Prelude, TouchIME, Treeline Bio, mBrace; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, RV More, Remedica Ltd; Financial Interests, Personal, Stocks/Shares: Treeline Biosciences; Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Personal, Other, stocks: mBrace; Financial Interests, Institutional, Funding, Research funding: Pfizer, Exelixis, PharmaMar, GSK, Teva, Taiho; Financial Interests, Personal, Funding, Research: Foundation Medicine; Non-Financial Interests, Personal, Member: ASCO, AACR, IASLC; Other, Personal, Other, Food/Beverage: Merck, PUMA, Merus; Other, Personal, Other, Other: Boehringer Ingelheim. G. Lozano-Ortega: Financial Interests, Institutional, Funding, Funding provided to BroadstreetHEOR: BMS. Y. Yuan: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. E.E. Korol, D. Ayers, M. Crabtree, L. Huria, E. Popoff: Financial Interests, Institutional, Funding, Funding provided to Broadstreet HEOR: BMS. C. Calvet: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. D.R. Camidge: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, Anheart, Anchiarno, Appolomics, AstraZeneca/Daiichi Sankyo, BeiGene, Dizal, Bio-Thera, Blueprint, BMS, Eisai, Elevation, Eli Lilly, EMD Serono, GSK, Helsinn, Hengrui, Hummingbird, Janssen, Kestrel, Medtronic, Mersana, Mirati, Nalo Therapeutics, Nuvalent, Onkure, Pfizer, Puma, Qilu, Regeneron, Ribon, Roche, Sanofi, Seattle Genetics, Takeda, Theseus, Turning Point, Xcovery; Financial Interests, Institutional, Funding: Inivata; Financial Interests, Institutional, Principal Investigator: AbbVie, AstraZeneca, Blueprint, Dizal, Inhibrx, Karyopharm, Nuvalent, Pfizer, Phosplatin, Psioxus, Rain, Roche/Genentech, Seattle Genetics, Takeda, Turning Point, Verastem.