University of Colorado, Aurora, CO
Robert Charles Doebele , Jessica Jiyeong Lin , Misako Nagasaka , Viola Weijia Zhu , Nashat Y. Gabrail , Lyudmila Bazhenova , Peter Meade Anderson , Benjamin J. Solomon , Arkadiusz Z. Dudek , Andrew William Pippas , Mihran Shirinian , Christina S Baik , Shanna Stopatschinskaja , D. Ross Camidge , Byoung Chul Cho , Alexander E. Drilon
Background: Repotrectinib is a next-generation ROS1/TRK inhibitor with > 90-fold greater potency than crizotinib against ROS1 and > 100-fold greater potency than larotrectinib against TRK. Preclinical studies demonstrated inhibitory activity of repotrectinib against ROS1 resistance mutations, including the solvent-front mutation (SFM) G2032R. In the phase 1 portion of the study, repotrectinib was found to be well tolerated with encouraging antitumor activity including a 91% confirmed overall response (cORR) in TKI-naïve ROS1+ NSCLC pts. In ROS1+ NSCLC pts who received 1 prior chemo and 1 prior TKI, the cORR was 57% at the clinical dose of 160 mg QD or above. Intra-cranial (IC) activity was observed in ROS1+ NSCLC pts with measurable CNS disease (100% IC-ORR in TKI-naïve and 75% IC-ORR in patients with 1 prior TKI). Encouraging antitumor activity was observed in pts with NTRK+ solid tumors. Methods: A global phase 2 study was initiated and is actively enrolling. The primary endpoint for the Phase 2 study is cORR assessed by BICR (Blinded Independent Central Review) using RECIST v1.1, in each expansion cohort in pts with advanced solid tumors that harbor a ROS1 or NTRK1/2/3 gene fusion. Secondary endpoints include duration of response (DOR), progression-free survival (PFS), overall survival (OS), IC-ORR, IC-PFS, and quality of life assessments. All pts need to have RECIST 1.1 measurable disease confirmed by BICR and ECOG performance score ≤1. Repotrectinib is administered at 160 mg QD for 14 days and, if tolerated, the dose can be increased to 160 mg BID. Approximately 320 pts (≥12 years old) will be enrolled into 6 defined expansion cohorts, depending on the status of previous treatment with TKIs and cancer types (see table below). Clinical trial information: NCT03093116.
Cohort # | Tumor Type | Prior Treatment | Sample Size (pts) |
---|---|---|---|
1 | ROS1+NSCLC | ROS1 TKI-naive | 55 |
2 | 1 Prior ROS1 TKI AND 1 Platinum-based Chemo | 100 | |
3 | 2 Prior ROS1 TKIs AND 1 Platinum-based Chemo | 40 | |
4 | 1 Prior ROS1 TKI and NO Prior Chemo OR Immunotherapy | Up to 30 | |
5 | NTRK+solid tumors | TRK TKI-naïve | 55 |
6 | TRK TKI-pretreated (up to 2 prior TKIs) | 40 |
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Abstract Disclosures
2023 ASCO Annual Meeting
First Author: Jessica Jiyeong Lin
2022 ASCO Annual Meeting
First Author: Misako Nagasaka
2023 ASCO Annual Meeting
First Author: Jialei Wang
2021 ASCO Annual Meeting
First Author: Haruko Daga