Phase 1/2 TRIDENT-1 study of repotrectinib in patients with ROS1+ or NTRK plus advanced solid tumors
Authors
Cho, B. C.Doebele, R. C.
Lin, J.
Nagasaka, M.
Baik, C.
Van der Wekken, A.
Velcheti, V.
Lee, K. H.
Liu, S.
Solomon, B.
Kao, S.
Krebs, Matthew G
Zhu, V.
Stopatschinskaja, S.
Camidge, R.
Drilon, A.
Affiliation
Yonsei Cancer Center, Severance Hospital, Seoul/KRIssue Date
2021
Metadata
Show full item recordAbstract
Introduction: Repotrectinib is a next-generation ROS1/TRK TKI with >90-fold greater potency than crizotinib and entrectinib against ROS1 and >100-fold greater potency than larotrectinib against TRK in engineered Ba/F3 cell proliferation assays. In the Phase 1 portion of TRIDENT-1 study, repotrectinib demonstrated encouraging overall clinical activity in patients (pts) with ROS1 fusion+ NSCLC and TRK fusion+ solid tumors, especially in those pts with ROS1+ NSCLC who are TKI naive. Methods: In Phase 1 portion of the study, the Recommended Phase 2 Dose (RP2D) for repotrectinib was determined to be 160 mg QD for 14 days followed by 160 mg BID if tolerated. Currently, this global trial (Clinical trial information: NCT03093116) is actively enrolling pts whose cancers harbor a ROS1 or NTRK1/2/3 fusion in six phase 2 expansion cohorts (see table). The primary endpoint for the Phase 2 portion is confirmed overall response rate (cORR) by Blinded Independent Central Review (BICR) using RECIST v1.1. An early interim analysis on 39 pts enrolled in Phase 2 was conducted using investigator assessment. Results: Phase 1: Utilizing a 22 July 2019 data cutoff, cORR was 91% by BICR in 11 ROS1 TKI-naïve pts with 5 responses ongoing. The median duration of response (DOR) for the 10 confirmed responders was 23.1 months (95% CI: 5.6enot reached [NR]) and median progression-free survival (PFS) was 24.6 months (95% CI: 7.2 e NR). As of 6 April 2020, with an additional 8.5 months of follow-up, 4 of the 5 previously responding TKI-naïve pts remained in a partial response (PR) per physician assessment data and 7 TKI-naïve pts remained on treatment, range (17.3+ - 34.2+ months). Phase 2: The early Phase 2 TRIDENT-1 dataset utilizing a July 10, 2020 data cutoff includes the first 39 treated pts across six cohorts who have had at least one post-baseline scan. Conclusion: Repotrectinib was well tolerated and continues to demonstrate encouraging overall clinical activity in pts with ROS1 fusion-positive NSCLC and TRK fusion-positive solid tumors. Keywords: repotrectinib TKI-naive response.Citation
Cho BC, Doebele RC, Lin J, Nagasaka M, Baik C, Van Der Wekken A, et al. MA11.07 Phase 1/2 TRIDENT-1 Study of Repotrectinib in Patients with ROS1+ or NTRK+ Advanced Solid Tumors. Journal of Thoracic Oncology. 2021 Mar;16(3):S174–5.Journal
Journal of Thoracic OncologyDOI
10.1016/j.jtho.2021.01.251Additional Links
https://dx.doi.org/10.1016/j.jtho.2021.01.251Type
Meetings and ProceedingsLanguage
enae974a485f413a2113503eed53cd6c53
10.1016/j.jtho.2021.01.251