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Phase 1/2 TRIDENT-1 study of repotrectinib in patients with ROS1+ or NTRK plus advanced solid tumors
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.
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.
Citations
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Abstract
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.
Description
Date
2021
Publisher
Collections
Keywords
Type
Meetings and Proceedings
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.