Abstract 596P
Background
Repotrectinib, a next-generation ROS1 and TRK tyrosine kinase inhibitor (TKI), has demonstrated durable activity and manageable safety in pts with ROS1+ NSCLC in the pivotal phase 1/2 TRIDENT-1 trial (NCT03093116). Here, we report efficacy and safety of repotrectinib in the Asia and China subpopulations in the TRIDENT-1 trial.
Methods
Pts with ROS1+ NSCLC were enrolled in distinct cohorts based on prior treatment. Recommended phase 2 dose was 160 mg once daily for 14 d, then 160 mg twice daily. Phase 2 primary endpoint was confirmed objective response rate (cORR).
Results
As of December 19, 2022, 41 of 71 pts in the TKI-naïve cohort were from Asia (median f/u 25 mo) with 11 from China (median f/u 17 mo). In the TKI-naïve pts from Asia, cORR (95% CI) was 88% (74–96); 12-mo and 18-mo duration of response (DOR) estimates were 82% (70–95) and 76% (61–90), respectively; 12-mo and 18-mo progression-free survival (PFS) estimates were 84% (72–96) and 75% (61–89), respectively. Of 56 pts in the 1 prior TKI and no prior chemo cohort, 23 were from Asia (median f/u 20 mo) with 11 from China (median f/u 16 mo). In these pts from Asia, cORR (95% CI) was 35% (16–57); 12-mo DOR and PFS estimates were 62% (29–96) and 48% (25–71), respectively. Results including intracranial activity and efficacy in pts from China are shown in the table. The most common any grade treatment-emergent adverse events (TEAEs) in pts from Asia (n = 195) were dizziness (63%), anemia (51%), and dysgeusia (48%); in pts from China (n = 73) were anemia (74%), constipation (52%), and dizziness (48%). Gr ≥ 3 TEAEs occurred in 45% and 51%, respectively. Treatment discontinuation due to TEAEs was 7% in both subpopulations.
Conclusions
In TRIDENT-1, repotrectinib showed durable clinical activity, intracranial response, and manageable safety in both TKI-naïve and -pretreated pts from Asia, including pts from China. Table: 596P
Repotrectinib efficacy in ROS1+ NSCLC
| TKI-naïve | 1 prior TKI no chemo | |||
| Asia (n = 41) | China (n = 11) | Asia (n = 23) | China (n = 11) | |
| cORR, n (%) [95% CI] a | 36 (88) [74–96] | 10 (91) [59–100] | 8 (35) [16–57] | 5 (46) [17–77] |
| CR, n (%) | 3 (7) | 2 (18) | 2 (9) | 0 |
| PR, n (%) | 33 (80) | 8 (73) | 6 (26) | 5 (46) |
| DOR, % (95% CI) | ||||
| 12-mo estimate | 82 (70–95) | 76 (47–100) | 62 (29–96) | 60 (17–100) |
| 18-mo estimate | 76 (61–90) | — | — | — |
| PFS, % (95% CI) | ||||
| 12-mo estimate | 84 (72–96) | 79 (52–100) | 48 (25–71) | 46 (13–78) |
| 18-mo estimate | 75 (61–89) | — | — | — |
| Intracranial ORR in pts with measurable baseline brain mets, n/N (%) [95% CI] a | 5/5 (100)b [48–100] | 1/1 (100)b [2–100] | 2/7 (29)b [4–71] | 1/2 (50)b [1–99] |
aBlinded independent central review. bAll PRs. CR, complete response; PR, partial response.
Clinical trial identification
NCT03093116.
Editorial acknowledgement
Medical writing support, under directions of the authors, was provided by Elaine Heatherington, PhD, of Bio Connections LLC.
Legal entity responsible for the study
Bristol Myers Squibb.
Funding
Bristol Myers Squibb.
Disclosure
S. Lu: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Hutchison MediPharma, ZaiLab, GenomiCare, Novartis, Yuhan Corporation, Mirati Therapeutics, Menarini, Daiichi Sankyo, Inc, D3 Bio Limited, Simcere, Takeda, Roche ; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Hansoh; Financial Interests, Personal, Other, Research grant: AstraZeneca, Hutchinson, BMS, Heng Rui, BeiGene, Roche, Hansoh. K. Goto: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Amgen K.K., Takeda Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Amgen Inc., Amoy Diagnosties Co., Ltd., AstraZeneca K.K., Bayer HealthCare Pharmaceuticals Inc., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb K.K., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Guardant Health Inc., Ono Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., Thermo Fisher Scientific K.K., Taiho Pharmaceutical Co., Ltd., Syneos Health Clinical K.K., Life Technologies Japan Ltd.; Financial Interests, Personal, Advisory Board: Janssen Pharmaceutical K.K., Medpace Japan K.K., Haihe Biopharma Co., Ltd.; Financial Interests, Personal and Institutional, Funding: Amgen Inc., Amgen K.K., AstraZeneca K.K., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Haihe Biopharma Co., Ltd., Ignyta,Inc., Janssen Pharmaceutical K.K., KISSEI Pharmaceutical CO., LTD., Merck Biopharma Co., Ltd., Kyowa Kirin Co., Ltd., Loxo Oncology, Inc., Medical&Biological Laboratoires Co., LTD., Merus N.V., MSD K.K., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sysmex Corporation., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Turning Point Therapeutics,Inc., Amgen Astellas BioPharma K.K., Bayer Yakuhin, Ltd., Blueprint Medicines Corporation., Craif Inc., Life Technologies Japan Ltd., NEC Corporation., Novartis Pharma K.K., Pfizer R&D Japan G.K., Turning Point Therapeutics,Inc.; Non-Financial Interests, Personal, Member: American Society of Clinical Oncology, The Japan Lung Cancer Society, Japanese Society of Medical Oncology, The Japanese Cancer Association. R.A. Soo: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BMS, Lily, Merck, Novartis, Pfizer, Roche, Taiho, Takeda, Yuhan, Thermo Fisher, Janssen, Merck Serono, Puma Biotech; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim. K.H. Lee: Financial Interests, Personal, Advisory Role: BMS, MSD, AstraZeneca, Pfizer, Eli Lilly. D.W. Lim: Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Board: MSD, Roche, BeiGene; Financial Interests, Institutional, Trial Chair, Grant funding for investigator-sponsored study: Bristol Myers Squibb; Financial Interests, Institutional, Steering Committee Member: Novartis. T. Kato: Financial Interests, Personal, Advisory Board, speaker, consultancy: AstraZeneca, Eli Lilly, Merck Biopharma, MSD; Financial Interests, Personal, Advisory Board, speaker: Pfizer, Amgen, Janssen; Financial Interests, Personal, Other, consultancy: Daiichi Sankyo, Takeda, Taiho; Financial Interests, Personal, Other, consultancy, speaker: Chugai; Financial Interests, Personal, Invited Speaker: Ono, Novartis, Bristol-Myers Squibbb, Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: BeiGene, Glaxo; Financial Interests, Personal, Advisory Board, Steering Committee: Roche; Financial Interests, Personal, Full or part-time Employment, Family member: Eli Lilly; Financial Interests, Institutional, Local PI: Chugai, MSD, Pfizer, Eli Lilly, AbbVie, Regeneron, Novartis, Amgen, Merck Biophama, BeiGene, Haihe Biopharma, Blueprint Medicines, Turning Point, Gilead, GSK, Janssen, Bayer, Takeda, Daiichi Sankyo; Financial Interests, Institutional, Steering Committee Member, Local PI: AstraZeneca. M. Tamiya: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly, Chugai Pharmaceutical, Boehringer Ingelheim, Taiho Pharmaceutical, Pfizer, Ono Pharmaceutical, Bristol Myers Squibb, MSD, Amgen; Financial Interests, Personal, Advisory Board: Pfizer. F. Ades: Financial Interests, Personal, Other, Employee: Bristol Myers Squibb. P.T. Wang: Financial Interests, Personal, Full or part-time Employment, Biostatistician employed full-time: BMS (Bristol Myers Squibb); Financial Interests, Personal, Stocks/Shares: BMS (Bristol Myers Squibb). 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 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, Therapex, JINTSbio, Hanmi, CHA Bundang Medical Center; Other, Personal, Other, Founder: DAAN Biotherapeutics. All other authors have declared no conflicts of interest.
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