Efficacy of Taletrectinib (AB-106/DS-6051b) in ROS1+ NSCLC: An Updated Pooled Analysis of U.S. and Japan Phase 1 Studies
Year: 2020
Type: article
Abstract: Introduction Taletrectinib (AB-106/DS-6051b) is an oral, potent selective ROS1 and pan-NTRK tyrosine kinase inhibitor (TKI). Preclinically, taletrectinib has activity against ROS1 G2032R solvent-front mutation. Methods Patients with ROS1+ NSCLC enrolled into two phase 1 studies conducted in United States (U101, NCT02279433) and Japan (J102, NCT02675491) were analyzed for objective response rate (ORR) by the Response Evaluation Criteria in Solid Tumors version 1.1, progression-free survival, and safety. Results A total of 22 patients with ROS1+ NSCLC out of the total 61 patients enrolled were analyzed. Taletrectinib was given at the oral dose of 400 mg, 600 mg, 800 mg, and 1200 mg once daily and 400 mg twice daily as part of the dose-escalation schema. Data cutoff was August 19, 2020. Median follow-up time for all 22 patients was 14.9 months (95% confidence interval [CI]: 4.1–33.8). A total of 18 patients with ROS1+ were assessable for response. The confirmed ORR for ROS1 TKI-naive patients (N = 9) was 66.7% (95% CI: 35.4–87.9) with a disease control rate of 100% (70.1–100). The confirmed ORR for crizotinib pretreated patients (N = 6) was 33.3% (95% CI: 9.7–70.0) with a disease control rate of 88.3% (95% CI: 443.6–97.0). The median progression-free survival for ROS1 TKI-naive patients (N = 11) was 29.1 months (95% CI: 2.6–not reached) and 14.2 months (95% CI: 1.5–not reached) for crizotinib-refractory only patients (N = 8). The most common treatment-related adverse events were alanine transaminase elevations (72.7%), aspartate transaminase elevations (72.7%), nausea (50.0%), and diarrhea (50.0%). Grade 3 or higher adverse events were alanine transaminase elevations (18.2%), aspartate transaminase (9.1%), and diarrhea (4.5%). Conclusions Taletrectinib (AB106/DS6051b) has a meaningful clinical activity in patients with advanced ROS1+ NSCLC who are ROS1 TKI-naive or crizotinib-refractory and a manageable safety profile.
Institutions: University of California, Irvine, University of California, Irvine Medical Center, UC Irvine Chao Family Comprehensive Cancer Center, National Cancer Center Hospital, Harvard University, Massachusetts General Hospital, Novartis Institutes for BioMedical Research, Kindai University, Dana-Farber Cancer Institute, National Hospital Organization Kyushu Cancer Center
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,000
Funders: Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Astellas Pharma US, AstraZeneca, Bayer, GlaxoSmithKline, Merck, Novartis, Roche, Sanofi, Ariad Pharmaceuticals, AbbVie, Meso Scale Diagnostics, Takeda Pharmaceuticals U.S.A., Taiho Pharmaceutical, Bayer Fund, Kissei, Parexel, Nichi-Iko Pharmaceutical, Boehringer Ingelheim Japan, Incyte, Otsuka America, Daiichi-Sankyo, Eisai, Kyowa Hakko Kirin, Astellas Pharma, Ono Pharmaceutical, Genentech, Merck Sharp and Dohme, Chugai Pharmaceutical, Ignyta, Bayer Yakuhin, Loxo Oncology, Daiichi Sankyo Europe
OpenAlex ID: W3094439638