Abstract 464P
Background
Laro, a highly selective, central nervous system (CNS)-active TRK inhibitor approved for adult and paediatric pts with TRK fusion cancer, showed rapid and durable responses in three phase I/II single-arm studies. The growth modulation index (GMI) is an intra-pt comparison that compares progression-free survival (PFS) on current therapy against time to progression or treatment failure (TTP) on most recent prior therapy. A GMI ratio ≥1.33 is a threshold for meaningful clinical activity. We report the GMI of 140 laro-treated pts with an extended follow-up, and of an expanded dataset with an additional 36 pts (176 pts in total) to assess the treatment effect of laro more extensively in pts with non-primary CNS TRK fusion cancer previously treated with ≥1 line of therapy.
Methods
Adult and paediatric pts treated in three laro clinical trials (NCT02576431, NCT02122913, and NCT02637687) were analysed retrospectively. TTP on prior line of therapy was investigator-assessed. PFS on laro was determined by an independent review committee (RECIST v1.1). Pts without progression were censored as of last visit. Median GMI, TTP, and PFS were estimated by Kaplan–Meier analyses. Data cut-off: July 2021.
Results
GMI results are shown in the table for the 140 pts with extended follow-up and the expanded dataset of 176 pts. Of the 53 pts with a GMI <1.33 in the expanded dataset, 10 were censored and continuing treatment. Of pts with 1, 2, or ≥3 prior lines of therapy, 47 (69%), 29 (59%), and 47 (80%) pts, respectively, had a GMI of ≥1.33 on laro. Median TTP on prior therapy was 3.0 months. Median PFS on laro was 19.6 months. Table: 464P
| Laro-treated pts (N) | Data cut-off | GMI | |||
| ≥1.33,n (%) | ≥1 to <1.33,n (%) | <1,n (%) | Median(95% CI) | ||
| 140 (Extended follow-up) | July 2020 (Italiano et al, ASCO 2021) | 103 (74) | 7 (5) | 30 (21) | 8.9(6.2–17.4) |
| July 2021 | 105 (75) | 6 (4) | 29 (21) | 7.9(5.8–11.7) | |
| 176 (Expanded dataset) | July 2021 | 123 (70) | 9 (5) | 44 (25) | 7.2(5.5–10.0) |
Conclusions
With extended follow-up, 75% of laro-treated pts with TRK fusion cancer had prolonged PFS compared with most recent prior therapy, irrespective of the number of prior lines of therapy received. This reinforces the benefits of using laro to treat pts with TRK fusion cancer.
Clinical trial identification
NCT02576431, NCT02122913, NCT02637687.
Editorial acknowledgement
Medical writing assistance was provided by Luke Springall, PhD, of Scion (London, UK), supported by Bayer HealthCare Pharmaceuticals, Inc.
Legal entity responsible for the study
Bayer.
Funding
Bayer.
Disclosure
A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, CHUGAI, GSK; Financial Interests, Institutional, Invited Speaker: Bayer, AstraZeneca, Roche, MSD, IPSEN, MERCK. A.E. Drilon: Financial Interests, Personal, Advisory Board: Ignyta/Genentech/Roche, Loxo Oncology/Bayer/Lilly, Takeda/Ariad/Millennium, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Helsinn Therapeutics, Beigene, BerGenBio, Hengrui Therapeutics, Exelixis, Tyra Biosciences, Verastem, MORE Health, AbbVie, 14ner/Elevation Oncology, Remedica Ltd., ArcherDX, Monopteros, Novartis, EMD Serono, Melendi, Liberum, Repare RX, Nuvalent, Merus, Chugai Pharmaceutical, EPG Health, Harborside Nexus, Liberum, RV More, Ology, Amgen, TouchIME, Janssen, Entos, Treeline Bio, Prelude, Applied Pharmaceutical Science, Inc; Financial Interests, Institutional, Research Grant: Pfizer, Exelixis, GSK, Teva, Taiho, PharmaMar; Financial Interests, Personal, Research Grant: Foundation Medicine; Financial Interests, Personal, Royalties: Wolters Kluwer; Non-Financial Interests, Personal, Other, Food/Beverage: Merck , Puma, Merus, Boehringer Ingelheim; Financial Interests, Personal, Other, CME honoraria: Medscape, OncLive, PeerVoice, Physicians Education Resources, Targeted Oncology, Research to Practice, Axis, Peerview Institute, Paradigm Medical Communications, WebMD, MJH Life Sciences, Med Learning, Imedex, Answers in CME, Medscape, Clinical Care Options, EPG Health, JNCC/Harborside, Liberum, Remedica Ltd. L. Shen: Financial Interests, Personal, Funding: Beijing Xiantong Biomedical Technology Co., Ltd, Qilu Pharmaceutical Co., Ltd, Zaiding Pharmaceutical (Shanghai) Co., Ltd, Jacobio Pharmaceuticals Co., Ltd.; Financial Interests, Personal, Advisory Role: Beihai Kangcheng (Beijing) Medical Technology Co.,Ltd., MSD, Merck, BI, Harbour; Financial Interests, Personal, Invited Speaker: Hutchison Whampoa, Hengrui, ZaiLab, CStone. D.S. Hong: Financial Interests, Personal, Research Grant: AbbVie, Adaptimmune, Amgen, AstraZeneca, Bayer, BMS, Daiichi-Sankyo, Eisai, Fate Therapeutics, Genentech, Genmab, Ignyta, Infinity, Kite, Kyowa, Lilly, Loxo Oncology, Merck, MedImmune, Mirati, MiRNA, Molecular Templates, Mologen, NCI-CTEP, Novartis, Pfize; Non-Financial Interests, Personal, Other, Travel: Loxo Oncology, MiRNA, ASCO, AACR, SITC, and Genmab; Financial Interests, Personal, Advisory Role: Alpha Insights, Axiom, Adaptimmune, Baxter, Bayer, Genentech, GLG, Group H, Guidepoint Global, Infinity, Janssen, Merrimack, Medscape, Numab, Pfizer, Seattle Genetics, Takeda, Trieza Therapeutics, Molecular Match, Presagia Inc; Financial Interests, Personal, Other, Founder: OncoResponse. C. van Tilburg: Financial Interests, Personal, Advisory Board: Bayer, Novartis. D.S.W. Tan: Financial Interests, Personal, Advisory Role: Novartis, Merck, Loxo, AstraZeneca, Roche, Pfizer; Financial Interests, Personal, Other, Travel: Pfizer, Boehringer Ingelheim, Roche; Honoraria: BMS, Takeda, Novartis, Roche, Pfizer; Financial Interests, Personal, Research Grant: Novartis, GSK, AstraZeneca. J.J. Lin: Financial Interests, Personal, Other, Personal fees: Pfizer, Genentech, C4 Therapeutics, Nuvalent, and Blueprint Medicines; Financial Interests, Personal, Other, Personal fees and other: Turning Point Therapeutics, Elevation Oncology, and Roche/Genentech; Financial Interests, Personal, Other: Hengrui Therapeutics, Neon Therapeutics, Relay Therapeutics, Novartis, and Bayer. S. Kummar: Non-Financial Interests, Personal, Other, Editor-in-Chief: Current Problems in Cancer (Elsevier); Financial Interests, Personal, Advisory Role: Boehringer Ingelheim, Springworks Therapeutics, Gilead, EcoR1, Seagen, Mundibiopharma Ltd, Bayer, Genome & Company HarbourBiomed, Oxfordbiotherapeutics; Financial Interests, Personal, Other, Co-founder and equity holder: PathomlQ. F. Doz: Financial Interests, Institutional, Advisory Role: Bayer, BMS, Roche, Celgene, LOXO Oncology, Servier, Tesaro, Servier; Non-Financial Interests, Personal, Other, Travel expenses: Bayer, BMS, and Roche. B. Geoerger: Financial Interests, Personal, Advisory Role: Bayer. M.S. Brose: Financial Interests, Personal, Research Grant: Loxo Oncology, Genentech, Eisai, Blueprint Medicines, Lilly, and Novartis; Financial Interests, Personal, Advisory Role: Bayer, Loxo Oncology, Genentech, AstraZeneca, and Lilly; Financial Interests, Personal, Other, Honoraria: Clinical Care Options, Medscape, OncLive, and PeerView. A. Briggs: Financial Interests, Personal, Advisory Role: Bayer. U.N. Lassen: Financial Interests, Personal, Advisory Role: Bayer, Pfizer, Novartis; Financial Interests, Personal, Research Grant: BMS, GSK, Pfizer and Roche. G. Vassal: Financial Interests, Personal, Advisory Role: Bayer, Hutchinson Pharma, Roche/Genentech, AstraZeneca, Pfizer, Ipsen, and BMS. K.N. Keating: Financial Interests, Personal, Full or part-time Employment: Bayer. R. Norenberg: Financial Interests, Personal, Other, External employee of Bayer, working for a CRO: Bayer. L. Dima: Financial Interests, Personal, Full or part-time Employment: Bayer. N. Brega: Financial Interests, Personal, Full or part-time Employment: Bayer. T. Laetsch: Financial Interests, Personal, Advisory Role: Novartis, Cellectis, Bayer, Loxo Oncology, Lilly, Deciphera, Jumo Health, Y-mAbs Therapeutics; Financial Interests, Personal, Research Grant: Pfizer, Novartis, Bayer, Loxo Oncology, AbbVie, Amgen, Atara Biotherapeutics, BMS, Lilly, Epizyme, GSK, Janssen, Jubilant Pharmaceuticals, Novella Clinical, and Servier. J. Garcia-Foncillas: Financial Interests, Personal, Other, Consulting, advisory, and honoraria speaker roles: Abbott, Amgen, Astellas, AstraZeneca, Biocartis, Boehringer Ingelheim, BMS, Bayer, Celgene, Eisai, Foundation Medicine, GSK, Hospira, Janssen, Lilly, Loxo Oncology, Merck Serono, MSD, Novartis, Pharmamar, Pfizer, Roche, Sanofi, Regeneron, Servier, Sysmex,.