Taletrectinib is a potent, next-generation, CNS-active, ROS1 tyrosine kinase inhibitor (TKI) with selectivity over TRKB. In previous reports from TRUST-I (NCT04395677), taletrectinib showed meaningful clinical efficacy and was well tolerated in pts with ROS1+ NSCLC (n=109) regardless of crizotinib (CRZ) pretreatment status. We report updated efficacy and safety data with ~1.5 yr follow-up.
TRUST-I is a multicenter, open-label, single-arm study with two cohorts: ROS1 TKI-naïve and CRZ-pretreated. Pts in both cohorts received taletrectinib 600 mg QD. Key study endpoints included IRC-confirmed ORR (cORR), DoR, disease control rate (DCR), PFS, and safety. A pooled analysis of ORR, PFS, and safety including pts from additional clinical trials was also conducted.
In the 109 pts from TRUST-I (enrolled prior to Feb 2022) the median follow-up was 18.0 mo in TKI-naïve (n=67) and 16.9 mo in CRZ-pretreated pts (n=42). cORR was 92.5% in TKI-naïve and 52.6% in CRZ-pretreated pts (Table). Median DoR (mDoR) and mPFS were not reached. Intracranial-ORR was 91.6%; ORR in pts with G2032R was 80.0%. In a pooled analysis with phase 1 studies, ORR was 89.5% and 50.0% for TKI-naïve and CRZ-pretreated pts, respectively; mPFS was 33.2 mo and 9.8 mo. In 178 pts treated at 600 mg QD, treatment-emergent adverse events (TEAEs) were 92.7%; most (64.0%) were grade 1–2. The most common TEAEs were increased AST (60.7%), increased ALT (55.6%), and diarrhea (55.6%). Neurological TEAEs (dizziness, 18.5%; dysgeusia, 12.4%) and discontinuations due to TEAEs (3.4%) were low. Further updated results will be presented.
Table. Efficacy in pts treated with taletrectinib.
| TRUST-1 | ROS1 TKI-Naïve (n=67) | CRZ-Pretreated (n=38) |
| Median follow-up | 18.0 (17.4-18.4) | 16.9 (11.7-18.0) |
| Confirmed ORR | 92.5 (83.4-97.5) | 52.6 (35.8-69.0) |
| Confirmed DCR | 95.5 (87.5-99.1) | 81.6 (65.7-92.3) |
| Median time to response, mo (Min,Max) | 1.4 (NE-NE) | 1.4 (1.3-1.4) |
| Pooled Data | ROS1 TKI-Naïve (n=78) | CRZ-Pretreated (n=46) |
| Confirmed ORRa | 89.5 (80.3-95.3) | 50.0 (34.6-65.4) |
| Median PFSa | 33.2 (23.5-NE) | 9.8 (5.6-18.4) |
| Data reported as mo (95% CI) unless specified. aData from evaluable patients from a pooled analysis from Phase 1 and 2 studies. CRZ, crizotinib; DCR, disease control rate; NE, not evaluable; ORR, overall response rate; PFS, progression-free survival; TKI, tyrosine kinase inhibitor. | ||
With additional follow-up, taletrectinib continued to demonstrate meaningful efficacy outcomes including high response rates, prolonged PFS, robust intracranial activity, activity against G2032R, and tolerable safety with low incidence of neurological AEs.
NCT04395677
Medical writing and editorial assistance were provided by Arpita Kulshrestha of Peloton Advantage, LLC, an OPEN Health company, and
funded by AnHeart Therapeutics, Inc.