264P - Updated analysis of entrectinib in a subset of Chinese (mainland China, Hong Kong, Taiwan) patients (pts) with NTRK fusion-positive (fp) solid tumours and ROS1-fp non-small cell lung cancer (NSCLC)

Background

Entrectinib is a CNS-active tyrosine kinase inhibitor that showed efficacy in pts with NTRK-fp solid tumours and ROS1-fp NSCLC from three phase 1/2 clinical trials (ALKA-372-001, EudraCT 2012-000148-88; STARTRK-1, NCT02097810; STARTRK-2, NCT02568267), including in a subset of Chinese (mainland China, Hong Kong, Taiwan) pts from STARTRK-2 (objective response rate [ORR]: 81% [NTRK-fp] and 63% [ROS1-fp]; data cutoff: 17 June 2021). We report updated data for this subset of patients, with a longer follow-up (enrolment/data cutoff: 17 Dec 2020/17 Dec 2021).

Methods

Chinese pts aged ≥18 years with locally advanced/metastatic NTRK-fp solid tumours or ROS1-fp NSCLC were enrolled. Tumour responses were assessed by blinded independent central review (BICR) per RECIST v1.1 at the end of Week 4 and every 8 weeks thereafter. Primary endpoints: ORR and duration of response (DoR). Key secondary endpoints: intracranial (IC) efficacy, time-to-event outcomes, and safety.

Results

The efficacy-evaluable population included 21 pts with NTRK-fp tumours (NSCLC n=11; sarcoma n=5; colon n=2; breast n=1; salivary n=1; thyroid n=1) and 38 pts with ROS1-fp NSCLC. Median survival follow-up was 16.7 mos (NTRK-fp tumours) and 36.6 mos (ROS1-fp NSCLC). In patients with NTRK-fp tumours, ORR was 81%. ORR in pts with ROS1-fp NSCLC was 66% (Table). The overall and IC results were in line with those reported in the overall study population. In the safety-evaluable NTRK-fp (n=32) and ROS1-fp (n=54) populations, 97% and 96% of pts reported treatment-related adverse events (TRAEs), respectively. Most were grade 1–2 and non-serious. TRAE-related discontinuation rates were 0% (NTRK-fp tumours) and 6% (ROS1-fp NSCLC).

Conclusions

This updated analysis with longer follow-up provides further evidence that entrectinib is associated with deep and durable responses in Chinese pts with NTRK-fp solid tumours or ROS1-fp NSCLC. Table: 264P

*By BICR; ^†Baseline CNS metastases by BICR; ^‡Data are not mature NE, not estimable

Clinical trial identification

Editorial acknowledgement

This study is sponsored by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance, under the direction of the authors, was provided by Claire White, PhD, of Ashfield MedComms, an Inizio company, and funded by F. Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

S. Lu: Financial Interests, Institutional, Invited Speaker: Hansoh, AstraZeneca, Roche; Financial Interests, Personal, Research Grant: AstraZeneca, Hutchison, BMS, Heng Rui BeiGene, Roche, Hansoh. C. Chiu: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Boehringer-Ingelhein, Bristol Myers Squibb, Chugai Pharmaceutical, Eli Lilly, Janssen, Merck KGaA, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical, Pfizer, Roche, Takeda; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Eli Lilly, Janssen, Merck KGaA, Merck Sharp & Dohme, Novartis, Roche. H.H.F. Loong: Financial Interests, Institutional, Invited Speaker: Boehringer-Ingelheim, MSD; Financial Interests, Personal, Invited Speaker: Eli Lilly, Illumina, Bayer, Guardant Health; Financial Interests, Personal, Advisory Board: Novartis, Takeda. C. Lin: Financial Interests, Personal, Other, Travel support: BeiGene, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Blueprint Medicines, Bristol Myers Squibb, Daiichi Sankyo, Novartis, AbbVie, PharmaEngine, Merck KGaA; Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, Roche. Z. Zhang: Financial Interests, Institutional, Full or part-time Employment: F. Hoffmann-La Roche Limited, Beijing, China. N. Zhao, T. Xu: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd. M. Hou: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd. All other authors have declared no conflicts of interest.