Abstract 43P
Background
NTRK gene fusions are oncogenic drivers in various cancers, including lung cancer. Laro is the first-in-class, highly selective, central nervous system (CNS)-active TRK inhibitor approved for use in pts with tumours harbouring an NTRK gene fusion. We report efficacy and safety with ctDNA analysis in pts with TRK fusion lung cancer treated with laro.
Methods
Pts treated with laro in two clinical trials (NCT02122913, NCT02576431) were analysed. NTRK gene fusions were determined by local testing before enrolment. Laro was administered at 100 mg twice daily. Response was assessed by an independent review committee (IRC) per RECIST v1.1. ctDNA was analysed using Guardant360 and GuardantOMNI.
Results
As of 20 July 2022, 30 pts (12 pts with CNS metastases) were enrolled. Pts received a median of two prior lines of systemic therapy, with 20 pts (67%) receiving two or more. Among 27 IRC-eligible pts, overall response rate was 74% (95% CI 54–89; three complete response [CR], 17 partial response [PR], four stable disease [SD], two progressive disease [PD] and one not evaluable). Median duration of response was 33.9 months (95% CI 9.5–not estimable [NE]); median follow-up was 22.9 months. Median progression-free survival was 33.0 months (95% CI 11.3–NE); median follow-up was 24.7 months. Median overall survival was 39.3 months (95% CI 17.2–NE); median follow-up was 23.1 months. Treatment-related adverse events were mostly Grade 1/2. ctDNA data were available for 14 pts. ctDNA analysis detected NTRK gene fusions in six of the 14 pts at treatment start. Baseline mutations were identified in nine pts. Eleven pts had prior immunotherapy. Best response to prior immunotherapy was one CR, one SD, two PD, two not evaluable and five unknown. The best responses to laro in these 11 pts were eight PR, two SD, and one PD.
Conclusions
Laro demonstrated durable responses, extended survival benefit and a favourable safety profile in pts with advanced lung cancer harbouring NTRK gene fusions. These results support the adoption of ctDNA next-generation sequencing panels that include NTRK gene fusions in clinical practice.
Clinical trial identification
NCT02122913, NCT02576431.
Editorial acknowledgement
Editorial assistance was provided by Anastasija Pesevska, PharmD, and Mel Ward, BA, both of Scion (London UK), supported by Bayer according to Good Publication Practice guidelines.
Legal entity responsible for the study
Bayer HealthCare Pharmaceuticals, Inc. and Loxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly and Company.
Funding
These studies were funded by Bayer HealthCare Pharmaceuticals, Inc. and Loxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly and Company.
Disclosure
A. Drilon: Financial Interests, Personal, Other, Received honoraria from/participated in advisory boards: Ignyta/Genentech/Roche, Loxo/Bayer/Lilly, Takeda/Ariad/Millennium, Turning Point Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Helsinn, 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, Merus, Chugai Pharmaceutical, Nuvalent, mBrace, AXIS, EPG Health, Harborside Nexus, Liberum, RV More, Ology; Financial Interests, Institutional, Funding: Pfizer, Exelixis, GSK, Teva, Taiho, PharmaMar; Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Personal, Other, Expenses: 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, EPG Health, JNCC/Harborside. J.J. Lin: Financial Interests, Personal, Other, Compensated consultant: Genentech; Financial Interests, Personal, Invited Speaker, Compensated consultant: C4 Therapeutics, Blueprint Medicines, Nuvalent, Bayer, Novartis, Mirati Therapeutics, Turning Point Therapeutics, Elevation Oncology, Regeneron; Financial Interests, Personal, Invited Speaker, Honoraria and travel support: Pfizer; Financial Interests, Institutional, Sponsor/Funding, Institutional research funding: 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, PeerView Institute, Northwell Health. D.S.W. Tan: Financial Interests, Personal, Other, Consultancy: Novartis, Merck, Loxo, AstraZeneca, Roche, Pfizer; Financial Interests, Personal, Other, Travel expenses: Pfizer, Boehringer Ingelheim, Roche; Financial Interests, Personal, Other, Honorarium: BMS, Takeda, Novartis, Roche, Pfizer; Financial Interests, Personal, Funding: Novartis, GSK, AstraZeneca. S. Kummar: Financial Interests, Personal, Other, Consulting/Advisory: Boehringer Ingelheim, SpringWorks Therapeutics, Gilead, EcoR1, Seagen, Mundibiopharma Ltd, Bayer, Mirati Therapeutics, Genome Insight, Genome & Company, Harbour Biomed; Financial Interests, Personal and Institutional, Leadership Role, Co-founder and equity holder: PathomlQ; Other, Personal, Advisory Role, Their spouse is scientific advisor: Cadila Pharmaceuticals Ltd; Other, Personal, Leadership Role, Their spouse is founder: Arxeon Inc. J.D. Patel: Financial Interests, Personal, Advisory Role: AbbVie, AstraZeneca, Takeda, Lilly. U.N. Lassen: Financial Interests, Personal, Advisory Board: Bayer, Pfizer, Novartis; Financial Interests, Personal, Funding: BMS, GSK, Pfizer, Roche. S. Leyvraz: Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Other, Travel grant support: Bayer. V. Moreno Garcia: Financial Interests, Personal, Other, Consultancy: Bayer, Pieris, BMS, Janssen; Financial Interests, Personal, Other, Travel support: Regeneron/Sanofi, BMS, Bayer; Financial Interests, Personal, Speaker’s Bureau: Nanobiotix, BMS, Bayer; Financial Interests, Personal, Other, Educational grant: Bayer, Medscape. L.S. Rosen: Financial Interests, Institutional, Funding: Bayer. B. Solomon: Financial Interests, Personal, Other, honoraria from or participated in advisory boards: AstraZeneca, Bayer. N. Neu: Financial Interests, Personal, Other, External employee: Bayer. D. Burcoveanu: Financial Interests, Personal, Full or part-time Employment: Bayer. C.E. Mussi: Financial Interests, Personal, Full or part-time Employment: Bayer. L. Shen: Financial Interests, Personal, Research Grant: 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 Therapeutics, Zai Lab, CStone Pharmaceuticals. All other authors have declared no conflicts of interest.