Abstract 72P
Background
Larotrectinib (laro) is the first-in-class, highly selective, CNS-active TRK inhibitor approved for tumour-agnostic use in patients (pts) with TRK fusion cancer based on a robust and durable objective response rate in both adult and paediatric pts with various tumour types. Here, we report data on adult pts with TRK fusion cancer treated in the first line.
Methods
Adult pts (≥18 years old) with treatment-naïve (no prior systemic therapy in the metastatic/unresectable setting, excluding surgery, radiotherapy and radioiodine) non-primary CNS TRK fusion cancer from 3 larotrectinib clinical trials (NCT02637687, NCT02122913, NCT02576431) were included. Responses were independent review committee (IRC)-assessed (RECIST v1.1).
Results
As of 20 July 2023, of 60 adult pts who were treatment-naive, 59 were eligible for IRC efficacy analyses. There were 11 different tumour types; the most common were salivary gland (n=18; 30%), thyroid cancer (n=15; 25%) and soft tissue sarcoma (n=14; 23%). Median age was 59 years (range 19–90). NTRK gene fusions were identified by NGS, FISH and RT-PCR in 54, 5 and 1 pt, respectively. Overall response rate was 68% (95% CI 54–79): 17 (29%) complete responses (CR; including 1 pathologic CR), 23 (39%) partial responses, 8 (14%) stable disease, 9 (15%) progressive disease and 2 (3%) not evaluable. Median time to first response was 1.8 months. Medians for duration of response, progression-free survival and overall survival (OS) were 59 months (95% CI 59–not estimable [NE]), 61 months (95% CI 15–NE) and not reached (range 1+ to 90+ months), at median follow-ups of 37, 36 and 48 months, respectively. The 5-year OS rate was 67% (95% CI 53–82). Treatment duration ranged from 0 to 74+ months (median 31 months). Treatment-related adverse events (TRAEs) were mainly Grade 1/2. Grade 3/4 TRAEs occurred in 9 (15%) pts. No pts discontinued due to a TRAE.
Conclusions
Laro demonstrates rapid and durable responses, extended survival and a favourable safety profile in adult pts without prior systemic therapy. This supports the use of laro in a first-line setting and the wider adoption of NGS panels that include NTRK gene fusions to identify adult pts who may benefit from targeted treatment.
Clinical trial identification
NCT02637687, NCT02122913, and NCT02576431.
Editorial acknowledgement
Medical writing assistance was provided by Patricia Badia Folgado, MSc, and editorial and typesetting assistance were provided by Melissa Ward, BA, both of Scion (a division of Prime, London, UK), supported by Bayer Healthcare Pharmaceuticals.
Legal entity responsible for the study
Bayer HealthCare Pharmaceuticals, Inc.
Funding
Bayer HealthCare Pharmaceuticals, Inc.
Disclosure
M. Casanova: Financial Interests, Personal, Advisory Role: AstraZeneca/Alexion, Bayer, Pfizer, BMS, Roche. A. Drilon: Financial Interests, Personal, Other, Honorarium: 14ner/Elevation Oncology, Amgen, AbbVie, ArcherDX, AstraZeneca, BeiGene, BerGenBio, Blueprint Medicines Corporation, Bristol Myers Squibb, Chugai Pharmaceutical, EcoR1, EMD Serono, Entos, Exelixis, Helsinn, Hengrui Therapeutics, Ignyta/Genentech/Roche, Janssen, Loxo/Bayer/Lilly, Merus, Monopteros, MonteRosa, Novartis, Nuvalent, Pfizer, Prelude, Regeneron, Repare RX, Springer Healthcare, Takeda/Ariad/Millenium, Treeline Bio, TP Therapeutics, Tyra Biosciences, Verastem; Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AnHeart Therapeutics, Bayer, EcoR1 Capital, LLC, Helsinn, MonteRosa, Novartis, Loxo/Lilly; Financial Interests, Personal, Other, Consulting: 14ner/Elevation Oncology, Boundless Bio, Entos, Innocare, MonteRosa, Nuvalent, Prelude, Treeline Bio, Zymeworks; Financial Interests, Institutional, Other, Associated research paid to institution: Foundation Medicine, GSK, PharmaMar, Taiho, Teva; Financial Interests, Personal, Ownership Interest, Equity: mBrace; Financial Interests, Personal, Ownership Interest, Copyright (filed/pending): Selpercatinib-Osimertinib; Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Personal, Other, Food/beverage expenses: Boehringer Ingelheim, Merck, Merus Puma; Financial Interests, Personal, Other, CME honoraria: Answers in CME, Applied Pharmaceutical Science, Inc, AXIS, Clinical Care Options, Doc Congress, EPG Health, Harborside Nexus, I3 Health, Imedex, Liberum, Medendi, Med Learning, Medscape, MedTalks, MJH Life Sciences, MORE Health, Ology, OncLive, Paradigm, Peerview Institute, PeerVoice, Physicians Education, Projects in Knowledge, Research to Practice, Remedica Ltd, Resources, RV More, Targeted Oncology, TouchIME, WebMD. R.S. McDermott: Financial Interests, Personal, Advisory Board: Amgen, Bayer, BMS, Clovis, Janssen, Pfizer, Astellas; Financial Interests, Personal, Invited Speaker: Ipsen, MSD; Financial Interests, Institutional, Other, Local PI: Astellas, Bayer, BMS, Clovis, Regeneron; Financial Interests, Institutional, Other, coordinating PI: MSD. A. Italiano: Financial Interests, Personal, Advisory Role: Bayer, Daiichi Sankyo, Epizyme, Ipsen, Roche, SpringWorks Therapeutics; Financial Interests, Personal, Research Grant: AstraZeneca, Bayer, Merck, MSD, Pharmamar, Roche. M. Tahara: Financial Interests, Personal, Advisory Role: AstraZeneca, Bayer, Lilly, Loxo Oncology, Merck Serono, MSD, Ono Pharmaceutical, Pfizer, Rakuten Medical; Financial Interests, Personal, Other, Consultancy: BMS, Eisai, MSD, Ono Pharmaceutical; Financial Interests, Personal, Other, Research funding: Bayer, Ono Pharmaceutical. M.S. Brose: Financial Interests, Institutional, Other, Research support via the University of Pennsylvania School of Medicine: Bayer, Loxo Oncology, Genentech, Eisai, Blueprint Medicines, Lilly, Novartis; Financial Interests, Personal, Other, Consultancy: Bayer, Loxo Oncology, Genentech, AstraZeneca, Lilly, PeerView; Financial Interests, Personal, Other, Honorarium: Clinical Care Options, Medscape, OncLive. J.J. Lin: Financial Interests, Personal, Other, Consultancy: Genentech, C4 Therapeutics, Blueprint Medicines Corporation, Nuvalent, Bayer, Novartis, Mirati Therapeutics, Turning Point Therapeutics, Elevation Oncology, Regeneron; Financial Interests, Personal, Other, Honorarium and travel support: Pfizer; Financial Interests, Institutional, Other, Research funds: Roche/Genentech, Hengrui Therapeutics, Turning Point Therapeutics, Neon Therapeutics, Relay Therapeutics, Bayer, Elevation Oncology, Linnaeus Therapeutics, Nuvalent, Novartis; Financial Interests, Personal, Other, CME funding: OncLive, MedStar Health, Northwell Health. D. Burcoveanu: Financial Interests, Personal, Full or part-time Employment: Bayer. N. Neu: Financial Interests, Personal, Full or part-time Employment, External employee: Bayer. C.E. Mussi: Financial Interests, Personal, Full or part-time Employment: Bayer. L. Shen: Financial Interests, Personal, Other, Research 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, Other, Consultancy: MSD, Merck, Boehringer Ingelheim, Harbour; Financial Interests, Personal, Invited Speaker: Hutchison Whampoa, Hengrui, ZaiLab, CStone. D.S. Hong: Financial Interests, Personal, Other, Research 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 expenses: Loxo Oncology, MiRNA, ASCO, AACR, SITC, Genmab; 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; Financial Interests, Personal, Ownership Interest, Advisor: Molecular Match, Presagia Inc; Financial Interests, Personal, Ownership Interest, Founder: OncoResponse.