390P - Entrectinib in Japanese patients (pts) with locally advanced/metastatic ROS1 fusion-positive (fp) NSCLC and NTRK-fp solid tumours

Background

Entrectinib is a ROS1/TRK tyrosine kinase inhibitor (TKI) with CNS activity. In an integrated analysis of three phase I/II trials (ALKA-372-001 EudraCT 2012-000148-88; STARTRK-1 NCT02097810; STARTRK-2 NCT02568267), entrectinib showed overall response rates (ORRs) of 67% in pts with ROS1-fp NSCLC and 61% in pts with NTRK-fp solid tumours (data cutoff: 2 Aug 2021). We present primary data for the subset of Japanese pts from STARTRK-2.

Methods

Adult Japanese ROS1/TRK TKI-naïve pts with locally advanced/metastatic ROS1-fp NSCLC or NTRK-fp solid tumours with ≥12 mos follow-up were included (enrolment/clinical cutoffs: 2 July 2020/2 Aug 2021). Tumour responses by blinded independent central review (BICR; RECIST v1.1), were evaluated at Wk 4 and then every 8 wks. Endpoints: ORR, duration of response, progression-free survival, intracranial (IC) efficacy (all by BICR), overall survival (OS) and safety.

Results

In total, 20 pts with ROS1-fp NSCLC and 10 pts with NTRK-fp solid tumours (5 salivary, 1 breast, 1 colorectal, 1 NSCLC, 1 sarcoma, 1 thyroid) were efficacy evaluable. For both cohorts, median survival follow-up was 38.6 mos and ORR was 70%. Overall data for these patients (Table) were aligned with the overall study population. The 24-mos OS rates were 65% (ROS1-fp NSCLC) and 90% (NTRK-fp solid tumours). In pts without baseline CNS mets by investigator, ORR was 76% (ROS1-fp NSCLC; n=13/17) and 75% (NTRK-fp solid tumours; n=6/8). In pts with baseline CNS mets by BICR (3 ROS1-fp; 1 NTRK-fp), one pt (NTRK-fp) had an IC response. In the safety population, treatment-related adverse events (TRAEs) led to treatment discontinuation/reduction/interruption in 22%/43%/65% of pts with ROS1-fp NSCLC (N=23) and 7%/43%/50% of pts with NTRK-fp solid tumours (N=14). No deaths due to a TRAE occurred.

Conclusions

Entrectinib showed deep and durable responses and manageable safety in Japanese pts with locally advanced/metastatic ROS1-fp NSCLC or NTRK-fp solid tumours Table: 390P

*BICR assessedNE, not estimable

Clinical trial identification

NCT02568267.

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 Tahmina Alam, MA, 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

H. Murakami: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharma, Takeda, Daiichi Sankyo, AbbVie, Ono Pharmaceutical, Bristol Myers Squibb Japan, MSD, Pfizer, Novartis, Lilly Japan, Taiho Pharmaceutical, Boehringer Ingelheim, Eisai Nihonkayaku; Financial Interests, Institutional, Principal Investigator: AstraZeneca, Chugai Pharma, Takeda, Daiichi Sankyo, AbbVie, IQvia; Financial Interests, Personal, Advisory Board: Chugai Pharma, GAIA BioMedicine. Y. Ohe: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Chugai, Eli Lilly, ONO, BMS, Boehringer Ingelheim, Bayer, Pfizer, MSD, Taiho, Nippon Kayaku, Kyowa Hakko Kirin; Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai, ONO, BMS, Kyorin, Celltrion, Amgen, Nippon Kayaku; Financial Interests, Personal, Research Grant: AstraZeneca, Chugai, Lilly, ONO, BMS, Kyorin, Dainippon- Sumitomo, Pfizer, Taiho, Novartis, Kissei, Ignyta, Takeda, Kissei, Daiichi-Sankyo, Janssen, LOXO; Financial Interests, Personal, Officer: JSMO, JLCS. H. Hayashi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd., Bristol Myers Squibb Co. Ltd, AstraZeneca K.K, Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K, Merck Biopharma Co. Ltd, MSD K.K., Novartis Pharmaceuticals K.K, Pfizer, Takeda Pharmaceutical Co. Ltd, Janssen Pharmaceutical K.K.; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb Co. Ltd, Daiichi Sankyo Co. Ltd., Eli Lilly Japan K.K, Shanghai Haihe Biopharm, Pfizer, AstraZeneca K.K; Financial Interests, Institutional, Funding: AstraZeneca K.K., Astellas Pharma Inc., MSD K.K., Ono Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co.,Ltd., Novartis Pharma K.K., grants, Pfizer Japan Inc., Bristol Myers Squibb Company, Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd., Daiichi; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., and Ono Pharmaceutical Co. Ltd.; Non-Financial Interests, Personal, Principal Investigator: Ono Pharmaceutical Co. Ltd. and Bristol Myers Squibb Co; Non-Financial Interests, Personal, Member: West Japan Oncology Group, Japan Society of Medical Oncology. T. Esaki: Financial Interests, Institutional, Invited Speaker: Chugai, Taiho, EP force, MSD, Daiichi Sankyo, Eli Lilly, Ono; Financial Interests, Personal, Research Grant: MSD, Novartis, Ono, Nihon Kayaku, IQVIA, Daiichi Sankyo, Chugai, Syneos Health Clinical, Pfizer, Dainippon Sumitomo, Quintiles, Eli Lilly, Prexel, Astellas, Astellas Amgen Biopharma; Financial Interests, Personal, Funding: Taiho, Chugai, Nihon Kayaku. T. Yamaguchi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, MSD, Merck, Towa Pharmaceutical and Bristol-Meyers Squibb; Financial Interests, Personal, Writing Engagements: Nippon Kayaku. H. Daga: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly, Chugai pharmaceutical. H. Tanaka: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai pharmaceutical, Boehringer Ingelheim, Eli Lilly, MSD, Ono pharmaceutical, Merck, Novartis, Takeda pharmaceutical, Pfizer, Daiichi Sankyo pharmaceutical, Taiho pharmaceutical, Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Chugai pharmaceutical, Merck, AstraZeneca, MSD, Eli Lilly, Ono pharmaceutical, Bristol Myers Squibb, Merck, Takeda pharmaceutical, Taiho pharmaceutical, Pfizer, Daiichi Sankyo pharmaceutical, AbbVie. T. Kozuki: Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical Co., AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical Co., Bristol Myers Squibb, Ono Pharmaceutical Co., MSD, Kyowa Hakko Kirin, Merck Biophama, Daiichi-Sankyo, Amgen, AbbVie, Sanofi, Eisai, Labcorp Development Japan; Financial Interests, Personal, Other, Consulting fees: Chugai Pharmaceutical Co., AstraZeneca, Ono Pharmaceutical Co., Pfizer Japan, Daiichi-Sankyo, Bayer, AbbVie; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical Co., AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical Co, Bristol Myers Squibb, Ono Pharmaceutical Co., MSD, Pfizer Japan, Kyowa Hakko Kirin, Nippon Boehringer Ingelheim, Merck Biophama, Nippon Kayaku, Novartis, Daiichi-Sankyo, Ta. S. Osborne: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd. W. Bordogna: Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd. K. Goto: Financial Interests, Personal, Invited Speaker: Amgen Inc., Amgen K.K., Amoy Diagnosties Co., Ltd., AstraZeneca K.K., Bayer HealthCare Pharmaceuticals Inc., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli ; Financial Interests, Personal, Advisory Board: Takeda Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., DAIICHI SANKYO Co., Ltd., Amgen Inc., Merck Biopharma Co., Ltd., Medpace Japan K.K; Financial Interests, Personal, Research Grant: Amgen Inc., Amgen Astellas BioPharma K.K., AstraZeneca K.K., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Haihe Biopharma Co., Ltd., Ign. All other authors have declared no conflicts of interest.