Positive topline data for repotrectinib across all ROS1-positive NSCLC cohorts of Phase 1/II TRIDENT-1 study.- Turning Point Therapeutics.

The primary objective of the TRIDENT-1 study is to determine the cORR (confirmed objective response rate ) based on BICR as assessed by RECIST 1.1, and the key secondary objectives include duration of response (DOR), progression free survival (PFS) and intracranial activity. The dataset utilizes a February 11, 2022 data cutoff date. The safety analysis included 380 treated patients from the pooled Phase 1 and Phase II portions of TRIDENT-1 across all cohorts, of which 287 patients were treated at the Phase II dose. The efficacy analyses included pooled patients from Phase 1 across all dose levels with an identified ROS1 fusion by next generation sequencing at baseline and Phase II patients. All patients received at least one dose of repotrectinib with at least four months of follow-up, and the majority of responders had at least six months of DOR follow-up.

Pooled Phase 1 and Phase II Topline Efficacy Analyses by BICR : ROS1-positive TKI-Naïve NSCLC (EXP-1; n=71 (8 from Phase 1 and 63 from Phase II) : In the ROS1-positive TKI-naïve advanced NSCLC population (EXP-1: n=71), the cORR was 79% (n=56/71; 95% CI: 68, 88), with 4 patients (6%) achieving a complete response (CR) and 52 patients (73%) achieving a partial response (PR). The cORR does not include one patient in an unconfirmed partial response (uPR) with tumor regression of -38% on the last scan, who remained on treatment awaiting the next scan as of the data cutoff date. DOR ranged from 1.4+ to 35.1+ months with probability of patients in a response at 6, 9, 12 and 18 months utilizing a Kaplan-Meier analysis, with a median duration of follow-up of 10.2 months. PFS ranged from 0+ to 40.4+ months with probability of patients remaining progression free at 6, 9, 12 and 18 months utilizing a Kaplan-Meier analysis, with a median duration of follow-up of 10.8 months.

ROS1-positive TKI-Pretreated NSCLC (EXP-2, EXP-3, and EXP-4; n=100) : i. In the ROS1-positive advanced NSCLC population pretreated with one prior TKI and prior platinum-based chemotherapy (EXP-2: n=26 (3 from Phase 1 and 23 from Phase II)), the cORR was 42% (n=11/26; 95% CI: 23, 63), with 1 patient (4%) achieving a CR and 10 patients (38%) achieving a PR. Duration of response ranged from 3.6 to 18.3+ months. ii. In the ROS1-positive advanced NSCLC population pretreated with two prior TKIs without prior chemotherapy (EXP-3: n=18 (1 from Phase 1 and 17 from Phase 2)), the cORR was 28% (n=5/18; 95% CI: 10, 54), with 1 patient (6%) achieving a CR and 4 patients (22%) achieving a PR. Duration of response ranged from 1.9+ to 20.3+ months. iii. In the ROS1-positive advanced NSCLC population pretreated with one prior TKI without prior chemotherapy (EXP-4: n=56 (3 from Phase 1 and 53 from Phase II)), the cORR was 36% (n=20/56; 95% CI: 23, 50), with 4 patients (7%) achieving a CR and 16 patients (30%) achieving a PR. The cORR does not include two patients with an uPR who both had tumor regressions of -47% on their last scans, both of whom remained on treatment awaiting their next scans as of the data cutoff date. Duration of response ranged from 1.9+ to 17.8 months. iv. Across the ROS1-positive TKI-pretreated advanced NSCLC population (EXP-2, EXP-3 and EXP-4), 17 patients had an identified ROS1 G2032R solvent front mutation detected, of which the cORR was 59% (n=10/17; 95% CI: 33, 82), with 1 patient (6%) achieving a CR and 9 patients (53%) achieving a PR. Duration of response ranged from 1.9+ to 20.3+ months.

TRIDENT-1 Topline Safety Analyses : Repotrectinib was generally well tolerated in a total of 380 patients with a safety and tolerability profile that was consistent with previously reported findings. The most commonly reported treatment emergent adverse event remained dizziness (61% all grade), of which 76% of patients who reported dizziness had a maximum severity of grade 1. The safety profile was comparable among the 287 patients who were treated at the Phase II dose.

As previously guided, the company anticipates discussing the topline BICR data with the FDA at a pre-NDA meeting this quarter. The company plans to present detailed study results, including intracranial activity, from the ROS1-positive advanced NSCLC cohorts of the TRIDENT-1 study, at a medical conference in the second half of 2022.