667P - Efficacy and safety of larotrectinib (laro) as first-line treatment for patients (pts) with tropomyosin receptor kinase (TRK) fusion cancer

Background

Laro is a highly selective, central nervous system (CNS)-active TRK inhibitor approved for tumour-agnostic use in pts with TRK fusion cancer based on a rapid, robust and durable objective response rate (ORR) in both adult and paediatric pts. We report data on laro-treated pts without prior systemic therapy.

Methods

Pts with treatment-naïve non-primary CNS TRK fusion cancer from three laro clinical trials were included. Laro was administered at 100 mg twice daily in most pts. Responses were assessed per independent review committee (IRC) using RECIST v1.1.

Results

As of July 2022, 84 pts were eligible for efficacy analyses by IRC; three pts (all adults) had known brain metastases at baseline. There were 12 different tumour types; the most common were soft tissue sarcoma (n=24; 29%), infantile fibrosarcoma (n=18; 21%), thyroid (n=15; 18%) and salivary gland (n=14; 17%). Median age was 31.5 years (range 0–90). The gene fusions involved were NTRK1 (n=30; 36%), NTRK2 (n=3; 4%) and NTRK3 (n=51; 61%). ORR was 80% (95% confidence interval [CI] 70–88): 42 (50%) complete response (CR; including six pathologic CR), 25 (30%) partial response, 10 (12%) stable disease, six (7%) progressive disease and one (1%) not evaluable. Median time to response was 1.8 months. Median duration of response was 44.5 months (95% CI 31.4–not estimable [NE]) at a median follow-up of 26.7 months. Medians for progression-free survival and overall survival (OS) were 46.2 months (95% CI 32.0–NE) and not reached, respectively, at median follow-ups of 30.4 and 41.3 months. The 48-month OS rate was 82% (95% CI 71–92). Treatment duration was 0–64+ months. Treatment-related adverse events (TRAEs) were mainly Grade 1/2. Grade 3/4 TRAEs occurred in 20 (24%) pts. Two pts discontinued due to a TRAE (malaise and hypoventilation occurred in one pt each).

Conclusions

Laro demonstrated rapid and durable responses, extended survival and a favourable safety profile in pts without prior systemic therapy. This supports the use of laro in a first-line setting and the wider adoption of next-generation sequencing panels that include NTRK gene fusions to identify pts who may benefit from treatment.

Clinical trial identification

NCT02576431, NCT02122913, NCT02637687.

Editorial acknowledgement

Medical writing assistance was provided by Patricia Badia Folgado, MSc, and editorial assistance was provided by Melissa Ward, BA, both of Scion Medica, London, UK.

Legal entity responsible for the study

Bayer HealthCare Pharmaceuticals, Inc.

Funding

Bayer HealthCare Pharmaceuticals, Inc.

Disclosure

D.S. Hong: Financial Interests, Personal, Funding: 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, Pfizer, Seattle Genetics, Takeda; Financial Interests, Personal, Other, Travel fees: Loxo Oncology, MiRNA, ASCO, AACR, SITC, 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 and Institutional, Leadership Role, Founder: OncoResponse; Financial Interests, Personal, Other, Consultancy: Alpha Insights, Axiom, Adaptimmune, Baxter, Bayer, Genentech, GLG, Group H, Guidepoint Global, Infinity, Janssen, Merrimack, Medscape, Numab, Pfizer, Seattle Genetics, Takeda, Trieza Therapeutics. R.S. McDermott: Financial Interests, Personal, Advisory Board: Amgen, Bayer, BMS, Clovis, Janssen, Pfizer; Financial Interests, Personal, Invited Speaker: Astellas, Ipsen, MSD; Financial Interests, Institutional, Principal Investigator, Local PI: Astellas, Bayer, BMS, Clovis, Regeneron; Financial Interests, Institutional, Principal Investigator, Coordinating PI: MSD. 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., Beihai Kangcheng (Beijing) Medical Technology Co., Ltd.; Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy: MSD, Merck, Boehringer Ingelheim, Harbour Biomed; Financial Interests, Personal, Speaker, Consultant, Advisor, Speaker: Hutchison Whampoa, Hengrui Therapeutics, ZaiLab, CStone. F. Doz: Financial Interests, Institutional, Advisory Board: Bayer, BMS, Roche, Celgene, Loxo Oncology, Servier, Tesaro; Financial Interests, Personal, Other, Travel expenses: Bayer, BMS, Roche; Financial Interests, Institutional, Speaker, Consultant, Advisor, Consultancy: Servier. M. Tahara: Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting/Advisory: Bayer, Merck Serono, MSD, Ono Pharmaceutical, Rakuten Medical, Pfizer, Lilly, AstraZeneca, Loxo Oncology; Financial Interests, Personal, Other, Honorarium: Eisai, MSD, Ono Pharmaceutical, BMS; Financial Interests, Personal, Research Funding: Bayer, Ono Pharmaceutica. V. Bernard-Gauthier: Financial Interests, Personal and Institutional, Full or part-time Employment: Bayer. R. Norenberg: Financial Interests, Personal and Institutional, Full or part-time Employment, External employee: Bayer. N. Brega: Financial Interests, Personal and Institutional, Full or part-time Employment: Bayer. T.W. Laetsch: Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy: Novartis, Cellectis, Bayer, Loxo Oncology, Lilly, Deciphera, Jumo Health, Y-mAbs Therapeutics; Financial Interests, Personal, Research Funding: Pfizer, Novartis, Bayer, Loxo Oncology, AbbVie, Amgen, Atara, Biotherapeutics, BMS, Lilly, Epizyme, GSK, Janssen, Jubilant Pharmaceuticals, Novella Clinical, Servier. A. Drilon: Financial Interests, Personal, Stocks or ownership, Equity: Treeline Bio; Financial Interests, Institutional, Other, Associated research paid to institution: Pfizer, Exelixis, GSK, Teva, Taiho, PharmaMar; Financial Interests, Personal, Ownership Interest, Copyright (filed/pending): Selpercatinib-Osimertinib ; Financial Interests, Personal, Other, Research: Foundation Medicine; Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Personal, Other, Food/beverage: Merck, Puma, Merus; Financial Interests, Personal, Other: Boehringer Ingelheim; Financial Interests, Personal, Other, CME honorarium: 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, Clinical Care Options, EPG Health, JNCC/Harborside, Liberum, Remedica Ltd., Lungevity; Financial Interests, Personal, Other, Honoraria advisory/boards: Ignyta, Genentech, Roche, Loxo Oncology, Bayer, Lilly, Takeda, Ariad, Millennium, Turning Point Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Helsinn Therapeutics, BeiGene, BerGenBio, Hengrui Therapeutics, Exelixis, Tyra Biosciences, Verastem, MORE Health, AbbVie, 14ner/Elevation Oncology, ArcherDX, Monopteros, Novartis, EMD Serono, Medendi, Repare RX, Nuvalent, Merus, Chugai Pharmaceutical, Remedica Ltd., mBrace, AXIS, EPG Health, Harborside Nexus, Liberum, RV More, Ology, Amgen, TouchIME, Janssen, Entos, Treeline Bio, Prelude, Applied Pharmaceutical Science, Inc., AiCME, i3 Health, MonteRosa, Innocare, Boundless Bio. All other authors have declared no conflicts of interest.