1289P - Pooled efficacy and safety from 2 pivotal phase II trials of taletrectinib in patients (Pts) with advanced or metastatic ROS1+ non-small cell lung cancer (NSCLC)

Background

Taletrectinib, a highly potent, next-generation, CNS-active, selective ROS1 tyrosine kinase inhibitor (TKI), has shown high and durable overall response rates (ORR), high intracranial (IC) response rates, prolonged progression-free survival (PFS), and robust activity against ROS1^G2032R with a favorable safety profile in pts with ROS1+ NSCLC. We report pooled data from the regional TRUST-I (NCT04395677) and global TRUST-II (NCT04919811) pivotal studies.

Methods

TRUST-I and TRUST-II are multicenter, single-arm, open-label, pivotal phase 2 studies of taletrectinib 600 mg QD. Endpoints included ORR (RECIST 1.1) by independent review committee (IRC), duration of response (DOR), PFS, and safety.

Results

As of March 29, 2024, 217 pts were evaluated for efficacy^a from TRUST-I (79%) and TRUST-II (21%): 130 TKI naive and 87 with 1 prior ROS1 TKI (median age: 56 y; 55% female; 94% Asian; 68% never smoked). In TKI-naive pts, 20% had prior chemotherapy and 21% had brain metastases. In pts with 1 prior ROS1 TKI, 38% had prior chemotherapy and 46% had brain metastases. In TKI-naive pts, cORR was 92% and IC-ORR was 76%; in pts with 1 prior ROS1 TKI, cORR was 54% and IC-ORR was 63% (Table). In TKI-naive pts, median DOR (mDOR) and median PFS (mPFS) were not reached (NR). In pts with 1 prior ROS1 TKI, mDOR was 24.9 mo and mPFS was 9.6 mo. Among 331 pts with ROS1+ NSCLC treated at 600 mg QD across phase 1 and 2 trials, the most frequent treatment-emergent adverse events (TEAEs) were increased AST (72%; 8% grade [G] ≥3), increased ALT (69%; 10% G≥3), and diarrhea (62%; 2% G≥3). Rates of neurologic TEAEs were low (dizziness, 20%) and mostly G1–2. Discontinuation (6%) and dose reductions (28%) due to TEAEs were low.

Conclusions

In a pooled population across two pivotal studies, taletrectinib showed high and durable overall responses, robust IC activity, and a favorable safety profile with low rates of neurologic AEs. Table: 1289P

Responses in patients with ROS1+ NSCLC^a

Data cutoff date: March 29, 2024^aPts who had ≥1 dose of taletrectinib, ≥1 IRC-assessed measurable lesion, and were enrolled ≥14 mo prior to data cut-off

Clinical trial identification

NCT04395677, NCT04919811.

Editorial acknowledgement

Medical writing and editorial support was provided by Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA.

Legal entity responsible for the study

AnHeart Therapeutics. A Nuvation Bio Company.

Funding

AnHeart Therapeutics, a Nuvation Bio Company.

Disclosure

M. Pérol: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, MSD, BMS, Lilly, Novartis, Takeda, Gritstone, Sanofi, Pfizer, Amgen, Janssen, GSK, Eisai, Ipsen, AstraZeneca, AbbVie, AnHeart Therapeutics, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, MSD, BMS, Boehringer Ingelheim, Takeda, Illumina, Pfizer, Medscape; Financial Interests, Personal, Advisory Board, Advisory board: Novocure; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Takeda, Boehringer Ingelheim; Financial Interests, Personal, Steering Committee Member: Roche, Sophia Genetics, PharmaMar, AnHeart Therapeutics; Financial Interests, Personal, Other, DMSB: Roche; Financial Interests, Institutional, Local PI: AstraZeneca, Amgen, Roche, AbbVie, Apollomics, AnHeart Therapeutics, Innate Pharma, Boehringer Ingelheim, Arrivent Biopharma, Daiichi Sankyo, Bayer; Financial Interests, Steering Committee Member: Lilly. N.A. Pennell: Financial Interests, Personal, Advisory Role: Merck, BMS, Pfizer, Genentech, Sanofi Genzyme, Novartis, Bayer, Summit Therapeutics, AnHeart, Takeda, J&J, Eli Lilly/Regeneron, Iovance. G. Liu: Non-Financial Interests, Personal, Other, Honorarium: Takeda, Amgen, AstraZeneca, Roche, Novartis, Merck, Pfizer, Jazz Pharmaceuticals; Financial Interests, Institutional, Funding: Takeda, AstraZeneca, Amgen, Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Takeda, AstraZeneca, Amgen, Boehringer Ingelheim. Y. Ohe: Financial Interests, Personal, Advisory Board: Amgen, AnHeart Therapeutics Inc, AstraZeneca, BMS, Celltrion, Nippon Kayaku, ONO, Pfizer, Takeda, PharmaMar, AnHeart; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Eisai, Eli Lilly, MSD, Novartis, ONO, Takeda; Financial Interests, Institutional, Local PI: AstraZeneca, Janssen, Amgen; Financial Interests, Personal and Institutional, Coordinating PI: Takeda, ONO; Non-Financial Interests, Leadership Role: JSMO, JLCS, JCOG; Non-Financial Interests, Member: ASCO. F.G.M. De Braud: Financial Interests, Personal, Invited Speaker: AMGEN, Ambrosetti, Ambrosetti, BMS, Dephaforum, ESO, Healthcare Research & Pharmacoepidemiology, Incyte, MSD, Merck Group, Nadirex, Pfizer, Roche, Sanofi, Seagen, Servier, Accmed, Dynamicom Education; Financial Interests, Personal, Other, Think Thank: MCCann Health; Financial Interests, Personal, Other, Consultant: Mattioli 1885; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other, Consultant Advisory Board: AstraZeneca, BMS, EMD Serono, Incyte, MSD, Menarini, NMS Nerviano Medical Science, Novartis, Pierre Fabre, Roche, Sanofi; Financial Interests, Personal, Other, Consultant Adv Board: Taiho; Financial Interests, Personal, Coordinating PI: BMS, Basilea Pharmaceutica International AG, DAICHI SANKIO Dev. Limited, Exelixis Inc., F.Hoffmann-LaRoche Ltd., IQVIA, Ignyta Operating Inc., Janssen-Cilag International NV, Kymab, Loxo Oncology Incorporated, MSD, MedImmune LCC, Merck KGAA, Merck Sharp & Dohme Spa, Novartis, Pfizer, Tesaro. M. Nagasaka: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Takeda, Novartis, EMD Serono, Pfizer, Eli Lilly and Company, Regeneron and Genentech; Financial Interests, Personal, Speaker, Consultant, Advisor, Vitrual tumor board: Caris Life Sciences; Financial Interests, Personal, Invited Speaker: Blueprint Medicines, Janssen, Mirati, Takeda; Financial Interests, Personal, Other, Travel support: AnHeart Therapeutics. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, Sanofi, Takeda, Touch Oncology, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Local PI, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, BeiGene, Boehringer Ingelheim GmbH, Bristol Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc., Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Non-Financial Interests, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Member, Member of the Scientiffic Advisory Committee: CAC Hospital Universitari Parc Taulí. B. Yan, S. Li, M. Chen: Financial Interests, Personal, Full or part-time Employment: AnHeart. L. Bazhenova: Financial Interests, Personal, Advisory Board: AnHeart Therapeutics, Bayer, Daiichi Sankyo, Genentech, Gilead Sciences, Inc., The Janssen Pharmaceutical Companies of Johnson & Johnson, Novocure, ORIC Regeneron Pharmaceuticals, Inc., Pfizer, Bayer, Sanofi, Teligene, BI. C. Zhou: Financial Interests, Personal, Advisory role, Consulting fees: Innovent Biologics, Qilu, Hengrui, TopAlliance Biosciences Inc.; Financial Interests, Personal, Other, Payment or honoraria from: Eli Lilly China, Sanofi, Boehringer Ingelheim, Roche, Merck Sharp & Dohme, Qilu, Hengrui, Innovent Biologics, Alice, C-Stone, LUYE Pharma, TopAlliance Biosciences Inc., Amoy Diagnostics, AnHeart. All other authors have declared no conflicts of interest.