Abstract 79P
Background
NTRK gene fusions are oncogenic drivers in multiple tumour types. Larotrectinib (laro) is the first-in-class, highly selective, central nervous system (CNS)-active TRK inhibitor approved for tumouragnostic use in patients (pts) with TRK fusion cancer. We report updated data on laro efficacy outcomes in pts with TRK fusion lung cancer, stratified by prior lines of systemic therapy and baseline Eastern Cooperative Oncology Group performance status (ECOG PS).
Methods
Pts with TRK fusion lung cancer treated with laro in two clinical trials (NCT02122913, NCT02576431) were included. Responses were assessed by an independent review committee per RECIST v1.1.
Results
As of 20 July 2023, 32 pts with TRK fusion lung cancer were enrolled. Median age was 55.5 years (range 25–81). The overall response rate (ORR) was 66% (95% confidence interval [CI] 47–81) in all pts and 67% (95% CI 35–90) in those with known baseline CNS metastases (n=12; Table). The ORR by 0 (n=1), 1 (n=10), 2 (n=9) or ≥3 (n=12) lines of prior systemic therapy was 100% (95% CI 3–100), 70% (95% CI 35–93), 67% (95% CI 30–93) and 58% (95% CI 28–85), respectively. The ORR by baseline ECOG PS 0 (n=9), 1 (n=18), 2 (n=3) or 3 (n=2) was 89% (95% CI 63–100), 56% (95% CI 33–82), 33% (95% CI 1–91), and 100% (95% CI 16–100), respectively. Median time to response, duration of response, progression-free survival and overall survival in all pts were 1.8 months (mo; range 1.5–7.3), 34 mo (95% CI 10–not estimable [NE]), 22 mo (95% CI 10–NE) and 39 mo (95% CI 17–NE), respectively. Treatment-related adverse events were predominantly Grade 1/2.
Conclusions
Laro demonstrated clinical benefit and favourable safety in pts with advanced/metastatic TRK fusion lung cancer, including across varying levels of prior treatment and ECOG PS, and in pts with known CNS metastases. These results support the wider adoption of next-generation sequencing panels that include NTRK gene fusions to identify pts who may benefit from targeted treatment.
Clinical trial identification
NCT02122913, NCT02576431.
Editorial acknowledgement
Medical writing assistance was provided by Anastasija Pesevska, PharmD, and editorial assistance was 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
These studies were funded by Bayer HealthCare Pharmaceuticals, Inc.
Table 79P| Known baseline CNS metastases | Prior lines of systemic therapy | Baseline ECOG PS | ||||||||
| Total N=32 | Yes n=12 | 0 n=1 | 1 n=10 | 2 n=9 | ≥3 n=12 | 0 n=9 | 1 n=18 | 2 n=3 | 3 n=2 | |
| ORR, % (95% CI) | 66 | 67 | 100 | 70 | 67 | 58 | 89 | 56 | 33 | 100 |
| (47–81) | (35–90) | (3–100) | (35–93) | (30–93) | (28–85) | (63–100) | (33–82) | (1–91) | (16–100) | |
| Best overall response, n (%) | ||||||||||
| Complete response | 4(13) | 0 | 0 | 2 (20) | 1 (11) | 1 (8) | 2 (22) | 2 (11) | 0 | 0 |
| Partial response | 17 (53) | 8 (67) | 1 (100) | 5 (50) | 5 (56) | 6 (50) | 6 (67) | 8 (44) | 1 (33) | 2 (100) |
| Stable disease | 7 (22) | 2 (17) | 0 | 2 (20) | 2 (22) | 3 (25) | 0 | 5 (28) | 2 (67) | 0 |
| Progressive disease | 2 (6) | 2 (17) | 0 | 0 | 0 | 2 (17) | 0 | 2 (11) | 0 | 0 |
| Not evaluable | 2 (6) | 0 | 0 | 1(10) | 1 (11) | 0 | 1 (11) | 1 (6) | 0 | 0 |
Disclosure
V. Moreno Garcia: Financial Interests, Personal, Other, Consultancy: Bayer, Pieris, Bristol Myers Squibb, Janssen; Financial Interests, Personal, Other, Travel expenses: Regeneron/Sanofi, Bristol Myers Squibb, Bayer; Financial Interests, Personal, Speaker’s Bureau: Nanobiotix, Bristol Myers Squibb, Bayer; Financial Interests, Personal, Other, Educational grant: Medscape/Bayer. A. Drilon: Financial Interests, Personal, Other, Honorarium: Elevation Oncology (formerly 14ner Oncology), Amgen, AbbVie, AnHeart Therapeutics, ArcherDX, AstraZeneca, Beigene, BergenBio, Blueprint Medicines, Bristol Myers Squibb, Boehringer Ingelheim, Chugai Pharmaceutical, EcoR1 Capital, 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, Zymeworks; Financial Interests, Personal, Advisory Board: Bayer, MonteRosa, AbbVie, EcoR1 Capital, Amgen, Helsinn, Novartis, Loxo/Lilly, AnHeart Therapeutics; Financial Interests, Personal, Other, Consultancy: MonteRosa, Innocare, Boundless Bio, Treeline Bio, Nuvalent, Elevation Oncology (formerly 14ner Oncology), Entos, Prelude, Bayer, Applied Pharmaceutical Science, Bristol Myers Squibb, Enlaza, Pfizer, Roche/Genentech; Financial Interests, Institutional, Other, Associated research paid to institution: Foundation Medicine, GSK, Teva, Taiho, PharmaMar; Financial Interests, Personal, Ownership Interest, Equity: mBrace, Treeline; Financial Interests, Personal, Ownership Interest, Copyright (US 18/041,617, pending): Selpercatinib-Osimertinib; Financial Interests, Personal, Royalties: Wolters Kluwer, UpToDate; Financial Interests, Personal, Other, Food/beverage expenses: Merck, Puma, Boehringer Ingelheim; Financial Interests, Personal, Other, CME honorarium: Answers in CME, Applied Pharmaceutical Science, Inc, AXIS, Clinical Care Options, Doc Congress, EPG Health, Harborside Nexus, I3 Health, Imedex, Liberum, Medendi, Medscape, Med Learning, MedTalks, MJH Life Sciences, MORE Health, Ology, OncLive, Paradigm, Peerview Institute, PeerVoice, Physicians Education, Projects in Knowledge, Resources, Remedica Ltd, Research to Practice, RV More, Targeted Oncology, TouchIME, WebMD. S. Kummar: Financial Interests, Personal, Other, Consulting/advisory role: Springworks Therapeutics, Seagen, Bayer, Genome & Company, HarbourBiomed, BPGbio Therapeutics, Oxford Biotherapeutics, Mundibiopharma, BPGbio, Inc., Gilead, Mirati, Fortress Biotech, Inc, GI Innovation Inc, XYone Therapeutics, Genome Insight, Aadi Biosciences, MOMA Therapeutics, Daiichi Sankyo; Financial Interests, Personal, Ownership Interest, Co-founder and equity holder: PathomlQ; Financial Interests, Personal, Other, Their spouse is a scientific advisor: Cadila Pharmaceuticals Ltd; Financial Interests, Personal, Ownership Interest, Their spouse is the founder: Arxeon Inc. J.J. Lin: Financial Interests, Personal, Other, Consultancy: Genentech, C4 Therapeutics, Blueprint Medicines, Nuvalent, Bayer, Novartis, Mirati Therapeutics, Turning Point Therapeutics, Elevation Oncology, Regeneron; Financial Interests, Personal, Other, Honoraria and travel support: Pfizer; Financial Interests, Institutional, Funding, Institutional 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, 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: Bristol Myers Squibb, Takeda, Novartis, Roche, Pfizer; Financial Interests, Personal, Funding, Research funding: Novartis, GSK, AstraZeneca. D.T. Rieke: Financial Interests, Personal, Advisory Role: Bayer, BeiGene; Financial Interests, Personal, Other, Travel expenses: Bayer, Johnson & Johnson; Financial Interests, Personal, Other, Honorarium: Lilly, Roche, Bristol Myers Squibb; Financial Interests, Personal, Funding, Research support: Seagen. 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. C. Qi: Financial Interests, Personal, Other, Consultancy: AstraZeneca, CARsgen Therapeutics; Financial Interests, Personal, Invited Speaker: Jiangsu Hengrui, Zai Lab, C-Stone Pharmaceuticals. All other authors have declared no conflicts of interest.