1373P - Efficacy and safety of taletrectinib in patients (Pts) with ROS1+ non-small cell lung cancer (NSCLC): Interim analysis of global TRUST-II study

Background

Taletrectinib, a next-generation, CNS-active, ROS1 TKI with selectivity over TRKB, demonstrated high overall and intracranial response rates, prolonged PFS, activity against G2032R, and was well tolerated in TRUST-I (NCT04395677). We report interim results of taletrectinib from the pivotal phase 2 trial, TRUST-II (NCT04919811), in advanced ROS1⁺ NSCLC pts from North America, Europe, and Asia.

Methods

TRUST-II, a multicenter, open-label, single-arm study in pts with ROS1⁺ tumors, has 4 cohorts: 1) NSCLC: ROS1 TKI-naive, ≤1 line of chemotherapy (CT); 2) NSCLC: 1 prior ROS1 TKI, ≤1 line of CT; 3) NSCLC: ≥2 ROS1 TKIs, ≤1 line of CT; and 4) solid tumors including NSCLC if ineligible for cohorts 1-3: ≤3 ROS1 TKIs, ≤2 lines of CT. Eligible pts had ECOG PS 0–1 and could have asymptomatic or treated/controlled CNS involvement. All pts started taletrectinib at 600 mg QD. The primary endpoint is independent review committee (IRC)-assessed confirmed objective response rate (cORR_IRC); other key endpoints include investigator-assessed cORR (cORR_INV), disease control rate (DCR), time to treatment response (TTR), DoR, PFS, and safety.

Results

Interim efficacy results are from 18 pts in cohort 1 and 22 pts in cohort 2 with ≥2 disease assessments (39% and 59% of pts had brain metastases, respectively). cORR_INV was 94% (17/18; 95% CI: 73, 100) in cohort 1 and 55% (12/22; 95% CI: 32, 76) in cohort 2; DCR was 100% and 91%, respectively. cORR_IRC will be presented. In both cohorts, median TTR was 1.4 mo; median DoR was not reached. As of March 31, 2023, 72 pts were included in the safety population that received ≥1 dose of taletrectinib. Median duration of exposure was 3.7 mo. Overall, 90% had a treatment-emergent adverse event (TEAE), mostly grade 1–2. The most common TEAEs were increased ALT (61%) or AST (61%), and nausea (38%). No treatment-related AE (TRAE) led to discontinuation or death; 24% of pts had a TRAE leading to dose reduction.

Conclusions

In this ongoing global pivotal phase 2 study, taletrectinib demonstrated robust and consistent clinical activity with TRUST-I, including high response rates and a tolerable safety profile in both TKI-naive and TKI-pretreated pts with ROS1⁺ NSCLC.

Clinical trial identification

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, New York, NY, USA.

Funding

AnHeart Therapeutics, New York, NY, USA.

Disclosure

M. Pérol: Financial Interests, Invited Speaker: Roche, Pfizer, Takeda, BMS, AstraZeneca, Amgen, MSD, Sanofi, Janssen-Cilag, Daiichi Sankyo, Medscape; Financial Interests, Expert Testimony: Roche, AstraZeneca, BMS; Financial Interests, Advisory Board: Roche, Eli Lilly, Pfizer, Merck Sharp & Dohme, Bristol Myers Squibb, Novartis, AstraZeneca, Takeda, Gritstone, Sanofi, GSK, Amgen, Daiichi Sankyo, Janssen-Cilag, Ipsen, AnHeart Therapeutics, Eisai, Roche, Eli Lilly, Pfizer, Merck Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, Takeda, GSK, Ipsen, AnHeart Therapeutics; Financial Interests, Principal Investigator: Roche, Eli Lilly, Pfizer, Merck Sharp & Dohme, Bristol Myers Squibb, Novartis, AstraZeneca, Takeda, Amgen, Daiichi Sankyo, AnHeart Therapeutics, AbbVie; Financial Interests, Sponsor/Funding: Roche, AstraZeneca, Chugai, Takeda, Boehringer Ingelheim. Y. Ohe: Financial Interests, Personal, Full or part-time Employment: AnHeart Therapeutics; Financial Interests, Institutional, Research Grant: AnHeart Therapeutics; Financial Interests, Personal and Institutional, Research Grant, personal fees: AstraZeneca, Chugai, Ono, BMS, Amgen, Nippon Kayaku, Eli Lilly, Pfizer, MSD, Taiho, Daiichi Sankyo, Janssen, Takeda; Financial Interests, Personal, Financially compensated role: Celltrion, Boehringer Ingelheim, Bayer, Eisai. S. Sugawara: Financial Interests, Institutional, Full or part-time Employment: AnHeart; Financial Interests, Institutional, Other: AstraZeneca, Chugai Pharma, MSD, Daiichi Sankyo, Bristol Myers Squibb, Nippon Boehringer Ingelheim, Ono Pharmaceutica, AbbVie, Amgen, Taiho Phamaceutical, Takeda; Financial Interests, Personal, Financially compensated role: Clinipace; Financial Interests, Speaker, Consultant, Advisor: AstraZeneca, Chugai Pharma, Ono Pharmaceutical, Bristol Myers Squibb, MSD, Nippon Boehringer Ingelheim, Pfizer, Taiho Pharmaceutical, Eli Lilly and Company, Novartis, Kyowa Kirin, Takeda, Nippon Kayaku, Merck, Amgen, AbbVie, Otsuka, Thermo Fisher Scientific, Towa Pharmaceutical. F.G.M. De Braud: Financial Interests, Personal, Speaker’s Bureau: BMS, Roche, Merck & Co, Kenilworth, NJ, Bayer, Ignyta, Dephaforum, Biotechespert, Prime Oncology, Pfizer , Nadirex, Ambrosetti, Incyte, Motore, Santia, Events, Fare Comunicazione, Itanet, Nadirex, ESO; Financial Interests, Personal, Advisory Board: Tiziana Life Sciences, BMS, Celgene, Novartis, Servier, Pharm Research Associated, Daiichi Sankyo, Ignyta, Amgen, Pfizer, Octimet Oncology, Incyte, Pierre Fabre, Eli Lilly, Roche, AstraZeneca, Gentili, Dephaforum, Merck & Co., Kenilworth, NJ, Bayer, Fondazione Menarini, Sanofi, Incyte, Taiho; Financial Interests, Institutional, Research Grant: Novartis, Roche, BMS, Celgene, Incyte, NMS, Merck KGaA, Kymab, Pfizer, Tesaro, Merck & Co.; Financial Interests, Personal, Principal Investigator: Novartis, Roche, BMS, Ignyta, Merck Sharp & Dohme, Kymab , Pfizer, Tesaro, MSD, MedImmune LCC, Exelixis Inc., Loxo Oncology Incorporated, Daiichi Sankyo Dev. Limited, Basilea Pharmaceutica International AG, Janssen-Cilag International NV, Merck KGAA; Financial Interests, Personal, Other, Consulting: BMS, Pierre Fabre, Mattioli 1885 , MCCann Health, MDS, IQVIA; Financial Interests, Personal, Other, Travel Expenses: Bristol Myers Squibb, Roche, Celgene, Amgen. J. Nieva: Financial Interests, Research Grant: Genentech, Merck; Financial Interests, Financially compensated role: Aadi Therapeutics, ANP technologies, Bioatla, AstraZeneca, Mindmed, Sanofi, Fujirebio, Naveris, Boeheringer-Ingelheim, G1 Therapeutics; Financial Interests, Other: Kalivir; Non-Financial Interests, Personal, Other, Dr. Nieva has a patent "Human Performance Measurements” licensed to Cansera: Cansera; Financial Interests, Ownership Interest: Cansera, Epic Sciences, Indee Bio, Quantgene. M. Nagasaka: Financial Interests, Personal, Speaker, Consultant, Advisor: Caris Life Sciences, AstraZeneca, Daiichi Sankyo, Novartis, Lilly, Pfizer, EMD Serono, Genentech, Mirati, Takeda, Janssen, Blueprint Medicine; Financial Interests, Institutional, Other, support for attending meetings and or travel: AnHeart Therapeutics. X. Zhang: Financial Interests, Personal, Full or part-time Employment: AnHeart Therapeutics. S. Li: Financial Interests, Personal, Full or part-time Employment: AnHeart Therapeutics. N.A. Pennell: Financial Interests, Advisory Board: AnHeart; Financial Interests, Advisory Role: Merck, Eli Lilly Loxo, Pfizer, Genentech, Janssen, Sanofi Genzyme, Novartis, Takeda, Bayer, Summit Therapeutics. All other authors have declared no conflicts of interest.