Abstract 77TiP
Background
Taletrectinib (AB-106/DS-6051b) is a next-generation, brain-penetrant, ROS1/ NTRK tyrosine kinase inhibitor (TKI) and has shown clinically meaningful effect and safety profile in ROS1+ Non-Small Cell Lung Cancer (NSCLC) patients in phase 1 studies (Fujiwara et al, Oncotarget 2018; 9(34): 23729-23737; Ou et al, JTO Clin Res Rep. 2020 Oct 21;2(1):100108). Taletrectinib has also demonstrated activity against ROS1 G2032R resistance mutation and CNS metastases in the ongoing phase 2 TRUST study (NCT04395677) in China. Also, taletrectinib has shown preliminary efficacy against NTRK-positive solid tumors in an ongoing phase 2 study (NCT04617054).
Trial design
TRUST-II study (NCT04919811) is a phase 2, global, multicenter, open-label, single-arm multi-cohort study evaluating the efficacy and safety of taletrectinib for ROS1 fusion-positive advanced metastatic NSCLC and other solid tumors. Taletrectinib will be given at 600 mg once daily in 21-day cycle. The patients with ROS1 fusions detected by local tests are eligible to enroll with retrospective confirmation by a central laboratory. The study consists of four cohorts: cohort 1: systemic chemotherapy naïve or ≤ one prior line and ROS1 TKI naïve NSCLC (N=53); cohort 2: previously treated with one ROS1 TKI (crizotinib or entrectinib) and with progression who are either chemotherapy naïve or ≤ one line of platinum and/or pemetrexed based therapy for NSCLC (N=46); cohort 3: ≤ 2 prior ROS1 TKIs and with progression who are either chemotherapy naïve or ≤ 2 lines of platinum and/or pemetrexed based therapy for NSCLC (N=10); and cohort 4: systemic chemotherapy naïve or ≤ 2 prior lines of chemotherapy, but ROS1-TKI naïve ROS1-positive solid tumor other than NSCLC ( N=10). The primary endpoint is objective response rate (ORR) (RECIST v1.1) by independent review committee (IRC) assessment for cohorts 1 and 2. Key secondary endpoints include IRC-assessed duration of response, IRC-assessed intra-cranial ORR, progression free survival (PFS), overall survival (OS), and safety. This study is currently recruiting in Japan, Republic of Korea, and USA. Additional accrual is planned in Canada, China, and European Union.
Clinical trial identification
NCT04919811.
Legal entity responsible for the study
The authors.
Funding
AnHeart Therapeutic Inc.
Disclosure
M. Nagasaka: Financial Interests, Personal, Speaker’s Bureau: Takeda; Financial Interests, Personal, Speaker’s Bureau: Blueprint Medicine; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Caris Life Sciences; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Mirati. S. Sugawara: Financial Interests, Personal, Speaker’s Bureau: Chugai Pharma; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Nippon Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly and Company; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: Kyowa Kirin; Financial Interests, Personal, Speaker’s Bureau: Yakult Honsha. T. Okamoto: Financial Interests, Personal, Speaker’s Bureau: Eli Lilly Japan; Financial Interests, Personal, Speaker’s Bureau: Johnson & Johnson; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Nippon Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical; Financial Interests, Institutional, Research Grant: λ Covidien Japan; Financial Interests, Institutional, Research Grant: Pfizer Japan; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Nippon Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical. N. Yanagitani: Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: ONO Pharmaceutical Co., Ltd.; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical Co., Ltd. K. Nosaki: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca KK; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly Japan K.K.; Financial Interests, Personal, Speaker’s Bureau: Nippon Kayaku Co., Ltd.; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: ONO Pharmaceutical Co., Ltd.; Financial Interests, Personal, Speaker’s Bureau: Pfizer Japan Inc.; Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca KK; Financial Interests, Personal and Institutional, Research Grant: AbbVie Inc.; Financial Interests, Personal and Institutional, Research Grant: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Personal and Institutional, Research Grant: Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal and Institutional, Research Grant: MSD K.K. T. Takahashi: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca KK; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly Japan K.K.; Financial Interests, Personal, Speaker’s Bureau: ONO Pharmaceutical Co., Ltd.; Financial Interests, Personal, Speaker’s Bureau: MSD K.K; Financial Interests, Personal, Speaker’s Bureau: Pfizer Japan Inc.; Financial Interests, Personal, Sponsor/Funding: Boehringer Ingelheim Japan; Financial Interests, Personal, Speaker’s Bureau: Roche Diagnostics; Financial Interests, Personal, Speaker’s Bureau: Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal, Speaker’s Bureau: Yakult Honsha Co., Ltd.; Financial Interests, Institutional, Funding: AstraZeneca KK; Financial Interests, Institutional, Funding: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Institutional, Funding: Eli Lilly Japan K.K.; Financial Interests, Institutional, Funding: ONO Pharmaceutical Co., Ltd.; Financial Interests, Institutional, Funding: MSD K.K.; Financial Interests, Institutional, Funding: Pfizer Japan Inc.; Financial Interests, Institutional, Funding: Amgen Inc.; Financial Interests, Institutional, Funding: Boehringer Ingelheim Japan. Y. Fujiwara: Financial Interests, Institutional, Principal Investigator: Amgen; Financial Interests, Institutional, Principal Investigator: AnHeart; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Chiome Bioscience; Financial Interests, Institutional, Principal Investigator: Chugai; Financial Interests, Personal, Speaker’s Bureau: Chugai; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: Daiichi Sankyo; Financial Interests, Institutional, Principal Investigator: Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Advisory Board: Otsuka Pharmaceutical; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Yakult; Financial Interests, Personal, Speaker’s Bureau: Taiho. H. Hayashi: Financial Interests, Personal and Institutional, Invited Speaker: Ono Pharmaceutical Co. Ltd; Financial Interests, Personal and Institutional, Speaker’s Bureau: Ono Pharmaceutical Co. Ltd; Financial Interests, Personal and Institutional, Advisory Board: Ono Pharmaceutical Co. Ltd; Financial Interests, Personal and Institutional, Research Grant: Ono Pharmaceutical Co. Ltd; Financial Interests, Personal and Institutional, Principal Investigator: Ono Pharmaceutical Co. Ltd; Financial Interests, Personal and Institutional, Sponsor/Funding: Ono Pharmaceutical Co. Ltd; Financial Interests, Personal and Institutional, Invited Speaker: Bristol Myers Squibb Co. Ltd; Financial Interests, Personal and Institutional, Speaker’s Bureau: Bristol Myers Squibb Co. Ltd; Financial Interests, Personal and Institutional, Advisory Board: Bristol Myers Squibb Co. Ltd; Financial Interests, Personal and Institutional, Research Grant: Bristol Myers Squibb Co. Ltd; Financial Interests, Personal and Institutional, Principal Investigator: Bristol Myers Squibb Co. Ltd; Financial Interests, Personal and Institutional, Sponsor/Funding: Bristol Myers Squibb Co. Ltd; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca K.K; Financial Interests, Personal and Institutional, Speaker’s Bureau: AstraZeneca K.K; Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca K.K; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca K.K; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca K.K; Financial Interests, Personal and Institutional, Invited Speaker: Boehringer Ingelheim Japan Inc; Financial Interests, Personal and Institutional, Speaker’s Bureau: Boehringer Ingelheim Japan Inc; Financial Interests, Personal and Institutional, Research Grant: Boehringer Ingelheim Japan Inc; Financial Interests, Personal and Institutional, Principal Investigator: Boehringer Ingelheim Japan Inc; Financial Interests, Personal and Institutional, Invited Speaker: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal and Institutional, Speaker’s Bureau: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal and Institutional, Advisory Board: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal and Institutional, Research Grant: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal and Institutional, Principal Investigator: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal and Institutional, Advisory Board: Daiichi Sankyo Co. Ltd.; Financial Interests, Personal and Institutional, Principal Investigator: Daiichi Sankyo Co. Ltd.; Financial Interests, Personal and Institutional, Speaker’s Bureau: Eli Lilly Japan K.K; Financial Interests, Personal and Institutional, Advisory Board: Eli Lilly Japan K.K; Financial Interests, Personal and Institutional, Research Grant: Eli Lilly Japan K.K; Financial Interests, Personal and Institutional, Speaker’s Bureau: Merck Biopharma Co. Ltd.; Financial Interests, Personal and Institutional, Advisory Board: Merck Biopharma Co. Ltd.; Financial Interests, Personal and Institutional, Principal Investigator: Merck Biopharma Co. Ltd.; Financial Interests, Personal and Institutional, Advisory Board: Shanghai Haihe Biopharm; Financial Interests, Personal and Institutional, Principal Investigator: Shanghai Haihe Biopharm; Financial Interests, Personal and Institutional, Principal Investigator: Taiho Pharmaceutical Co. Ltd; Financial Interests, Personal and Institutional, Speaker’s Bureau: Pfizer; Financial Interests, Personal and Institutional, Principal Investigator: Pfizer; Financial Interests, Personal and Institutional, Advisory Board: Pfizer; Financial Interests, Personal and Institutional, Speaker’s Bureau: Takeda Pharmaceutical Co. Ltd; Financial Interests, Personal and Institutional, Advisory Board: Takeda Pharmaceutical Co. Ltd; Financial Interests, Personal and Institutional, Principal Investigator: Takeda Pharmaceutical Co. Ltd; Financial Interests, Institutional, Principal Investigator: SymBio Pharmaceuticals Limited; Financial Interests, Institutional, Principal Investigator: AbbVie Inc, inVentiv Health Japan. J. Nieva: Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Personal, Advisory Role: Astra Zeneca; Financial Interests, Personal, Advisory Role: Naveris; Financial Interests, Personal, Advisory Role: Fujirebio; Financial Interests, Personal, Ownership Interest: Cansera; Financial Interests, Personal, Ownership Interest: Quantgene; Financial Interests, Personal, Ownership Interest: Indee. L.E. Raez: Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Genentech/roche; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Lilly Oncology; Financial Interests, Institutional, Research Grant: LOXO; Financial Interests, Institutional, Research Grant: Nant Health; Financial Interests, Institutional, Research Grant: Syndax; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Novartis. A. Dimou: Financial Interests, Institutional, Principal Investigator: Novartis; Financial Interests, Institutional, Principal Investigator: Syntrix Pharmaceuticals; Financial Interests, Institutional, Other, Honoraria: Roche/Genentech; Financial Interests, Institutional, Advisory Board, Funds paid to Mayo Clinic to support research in cancer: TP Therapeutics. N. Pennell: Financial Interests, Personal and Institutional, Research Grant: Mirati; Financial Interests, Personal, Advisory Role: Mirati; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Genentech; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Sanofi-Genzyme-Regeneron; Financial Interests, Personal, Advisory Role: Astrazeneca; Financial Interests, Personal, Advisory Role: Eli Lilly-LOXO; Financial Interests, Personal, Advisory Role: G1 Therapeutics; Financial Interests, Personal, Advisory Role: Xencor; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim. G. Liu: Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Speaker’s Bureau: AbbVie; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Speaker’s Bureau: Jazz; Financial Interests, Personal, Advisory Board: Jazz; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca; Financial Interests, Personal and Institutional, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca; Financial Interests, Personal and Institutional, Sponsor/Funding: AstraZeneca; Financial Interests, Personal and Institutional, Invited Speaker: Takeda; Financial Interests, Personal and Institutional, Speaker’s Bureau: Takeda; Financial Interests, Personal and Institutional, Advisory Board: Takeda; Financial Interests, Personal and Institutional, Principal Investigator: Takeda; Financial Interests, Personal and Institutional, Sponsor/Funding: Takeda. S.I. Ou: Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: BeiGene; Financial Interests, Personal, Advisory Board: JNJ/Janssen; Financial Interests, Personal, Advisory Board: Elevation Oncology; Financial Interests, Personal, Stocks/Shares: Turning Point Therapeutics; Financial Interests, Personal, Stocks/Shares: Elevation Oncology. T. Seto: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Personal, Speaker’s Bureau: Covidien Japan; Financial Interests, Personal, Speaker’s Bureau: Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly Japan; Financial Interests, Personal, Speaker’s Bureau: Kyowa Hakko Kirin; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Mochida Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Nippon Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Novartis Pharma; Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Pfizer Japan; Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Takeda Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Towa Pharmaceuticall; Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Eli Lilly Japan; Financial Interests, Institutional, Research Grant: Kissei Pharmaceutical; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Novartis Pharma; Financial Interests, Institutional, Research Grant: Pfizer Japan; Financial Interests, Institutional, Research Grant: Takeda Pharmaceuticall. Y. Ohe: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: ONO; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Invited Speaker: Nippon Kayaku; Financial Interests, Personal, Invited Speaker: Kyowa Hakko Kirin; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Chugai; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: ONO; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Kyorin; Financial Interests, Institutional, Research Grant: Dainippon- Sumitomo; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Kissei; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: LOXO; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Chugai; Financial Interests, Personal, Advisory Board: ONO; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Kyorin; Financial Interests, Personal, Advisory Board: Celltrion; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Nippon Kayaku; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: AnHeart Therapeutics Inc. All other authors have declared no conflicts of interest.