628P - Efficacy and safety of larotrectinib as first-line treatment for patients (pts) with TRK fusion cancer: An updated analysis

Background

Larotrectinib is the first-in-class, highly selective, CNS-active TRK inhibitor approved for tumour-agnostic use in pts with TRK fusion cancer. We report data on pts with TRK fusion cancer treated with larotrectinib in the first line.

Methods

Pts with treatment-naïve (no prior systemic therapy, excluding surgery and radioiodine, in the metastatic/unresectable setting) non-primary CNS TRK fusion cancer from 3 larotrectinib clinical trials (NCT02637687 [SCOUT], NCT02122913, NCT02576431) were included. Responses were independent review committee (IRC)-assessed (RECIST v1.1). Pts enrolled in SCOUT were permitted to stop larotrectinib in the absence of on-treatment progression (wait-and-see).

Results

As of 20 July 2023, of 101 pts enrolled (60 adults and 41 paediatrics [paeds]), 100 were eligible for IRC efficacy analyses. Four pts had baseline CNS metastases. There were 14 different tumour types; the most common were soft tissue sarcoma (30%), infantile fibrosarcoma (18%), salivary gland (18%) and thyroid (17%). Median age was 37 years (range 0–90). NTRK gene fusions were detected by NGS, FISH, PCR and an unknown method in 80, 12, 7 and 1% of pts, respectively. ORR was 77% (95% CI 68–85): 47% CR (including 10% pathologic CR), 30% PR, 11% SD, 9% PD and 3% not evaluable. ORR was 68% (95% CI 54–79) and 90% (95% CI 77–97) in adults and paeds, respectively. In all pts, median DoR, PFS and OS was 59 months (mo; 95% CI 33–not estimable [NE]), 61 mo (95% CI 33–NE) and not reached, respectively, at median follow-ups of 34, 36 and 50 mo. The 5-year OS rate was 76% (95% CI 65–86). Treatment duration was 0–6.4+ years. At data cut-off, 25 (61%) paeds enrolled in SCOUT had participated in ‘wait-and-see’. Treatment-related adverse events (TRAEs) were mainly Grade 1/2. Grade 3/4 TRAEs occurred in 26% of pts. One pt discontinued due to a TRAE (hypoventilation).

Conclusions

Larotrectinib continues to demonstrate rapid and durable responses, extended survival and a favourable safety profile in pts without prior systemic therapy. This supports the use of larotrectinib in a first-line setting and the wider adoption of NGS panels that include NTRK gene fusions to identify pts who may benefit from treatment.

Clinical trial identification

NCT02122913; NCT02637687; NCT02576431.

Editorial acknowledgement

Medical writing assistance was provided by Patricia Badia Folgado, MSc, and editorial and typesetting assistance was provided by Melissa Ward, BA, both of Scion (a division of Prime, London, UK).

Legal entity responsible for the study

Bayer Healthcare Pharmaceuticals, Inc.

Funding

Bayer Healthcare Pharmaceuticals, Inc.

Disclosure

D.S. Hong: Financial Interests, Institutional, Research Funding: AbbVie, Adaptimmune, AstraZeneca, Amgen, 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: Loxo Oncology, MiRNA, ASCO, AACR, SITC, Genmab; Financial Interests, Personal, Speaker, Consultant, Advisor: 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. L. Shen: Financial Interests, Institutional, 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, Speaker, Consultant, Advisor, Consultancy: MSD, Merck, Boehringer Ingelheim, Harbour Biomed; Financial Interests, Personal, Invited Speaker: Hutchison Whampoa, Hengrui Therapeutics, ZaiLab, CStone. D. Orbach: Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy: Bayer, Roche; Financial Interests, Institutional, Research Funding: Roche. R.S. McDermott: Financial Interests, Personal, Advisory Board: Amgen, Bayer, Clovis, Janssen, BMS, Pfizer; Financial Interests, Personal, Invited Speaker: Astellas, Ipsen, MSD; Financial Interests, Institutional, Local PI: Astellas, Bayer, BMS, Clovis, Regeneron; Financial Interests, Institutional, Coordinating PI: MSD. A. Italiano: Financial Interests, Personal, Advisory Role, Advisory role/honoraria: Bayer, Daiichi Sankyo, Epizyme, Ipsen, Roche, SpringWorks Therapeutics; Financial Interests, Institutional, Research Grant: AstraZeneca, Bayer, Merck, MSD, PharmaMar, Roche. M. Tahara: Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting/advisory fees: AstraZeneca, Bayer, Lilly, Loxo Oncology, Merck Serono, MSD, Ono Pharmaceutical, Pfizer, Rakuten Medical; Financial Interests, Personal, Other, honoraria: BMS, Eisai, MSD, Ono Pharmaceutical; Financial Interests, Institutional, Research Funding: Bayer, Ono Pharmaceutical. V. Bernard-Gauthier, C.E. Mussi, E.A. De La Cuesta: Other, Personal, Full or part-time Employment, Employee of: Bayer. N. Neu: Other, Personal, Full or part-time Employment, External employee of: Bayer. T. Laetsch: Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy: Bayer, Cellectis, Deciphera, Jumo Health, Lilly, Loxo Oncology, Novartis, Y-mAbs Therapeutics; Financial Interests, Institutional, Research Funding: AbbVie, Amgen, Atara, Biotherapeutics, Bayer, BMS, Epizyme, GSK, Janssen, Jubilant Pharmaceuticals, Lilly, Loxo Oncology, Novartis, Novella Clinical, Pfizer, Servier. A.E. Drilon: Financial Interests, Personal, Advisory Board: 14ner/Elevation Oncology, AbbVie, AiCME, Amgen, Applied Pharmaceutical Science, Inc, ArcherDX, AstraZeneca, AXIS, BeiGene, BerGenBio, Blueprint Medicines, Boundless Bio, Chugai Pharmaceutical, EMD Serono, Entos, EPG Health, Exelixis, Harborside Nexus, Helsinn Therapeutics, Hengrui Therapeutics, i3 Health, Ignyta/Genentech/Roche, Innocare, Janssen, Liberum, Loxo Oncology/Bayer/Lilly, mBrace, Medendi, Merus, Monopteros, MonteRosa, MORE Health, Novartis, Nuvalent, Ology, Pfizer, Prelude, Remedica Ltd, Repare RX, RV More, Takeda/Ariad/Millennium, TouchIME, Treeline Bio, Turning Point Therapeutics, Tyra Biosciences, Verastem; Financial Interests, Personal, Other, Equity: Treeline Bio; Financial Interests, Institutional, Research Funding: Exelixis, GSK, Pfizer, PharmaMar, Taiho, Teva, Foundation Medicine; Other, Personal and Institutional, Ownership Interest, copyright (filed/pending): Selpercatinib-Osimertinib; Financial Interests, Personal and Institutional, Royalties: Wolters Kluwer; Financial Interests, Personal, Other, food/beverage funding: Boehringer Ingelheim, Merck, Merus, Puma, CME; Financial Interests, Personal, Other, honoraria: CME, Axis, Clinical Care Options, EPG Health, Imedex, JNCC/Harborside, Liberum, Lungevity, Med Learning, Medscape, MJH Life Sciences, OncLive, Paradigm Medical Communications, Peerview Institute, PeerVoice, Physicians Education Resources, Research to Practice, Targeted Oncology, WebMD; Financial Interests, Personal, Officer, honoraria: Remedica Ltd. All other authors have declared no conflicts of interest.