Efficacy and Safety of Taletrectinib in Patients With ROS1+ NSCLC: Updated Safety Analysis From the Phase 2 TRUST-I and TRUST-II Studies
Amanda Herrmann,1 Jorge J. Nieva,2 Misako Nagasaka,3 Geoffrey Liu,4 Scott Owen,5 Xue Meng,6 Pilar Garrido,7 Feiwu Ran,8 Wei Wang,8 Clara Li,8 Xianyu Zhang,8 Lyudmila Bazhenova1
1Moores Cancer Center, University of California San Diego, San Diego, CA, USA; 2Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA; 3University of California Irvine School of Medicine and Chao Family Comprehensive Cancer Center, Orange, CA, USA; 4Princess Margaret Cancer Centre, Temerty School of Medicine, University of Toronto, Toronto, ON, Canada; 5McGill University Health Centre, Montreal, QC, Canada; 6Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China; 7University Hospital Ramón y Cajal, Madrid, Spain; 8Nuvation Bio Inc., New York, NY, USA
Presented at the 2026 Targeted Therapies of Lung Cancer Meeting | February 18–21, 2026 | Huntington Beach, CA, USA
For more information, please contact Dr Amanda Herrmann: aherrmann@health.ucsd.edu
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Background
- Taletrectinib is a next-generation, CNS-active, selective ROS1 TKI that has shown activity against the G2032R resistance mutation1,2
- Taletrectinib has been approved in the United States, Japan, and China for the treatment of patients with locally advanced or metastatic ROS1+ NSCLC3-5
- In two Phase 2 studies, TRUST-I (NCT04395677) and TRUST-II (NCT04919811), taletrectinib showed robust efficacy and a manageable safety profile in TKI-naïve and TKI-pretreated patients with advanced ROS1+ NSCLC6
- Here we report efficacy data from TRUST-I and TRUST-II, and updated pooled safety results with longer follow-up, including more detailed characterization of TEAEs of clinical interest
Methods
- The study designs of TRUST-I and TRUST-II have been previously reported6
- The efficacy population included patients from TRUST-I and TRUST-II with ≥1 measurable lesion(s) at baseline per RECIST v1.1 by IRC who started treatment on taletrectinib 600 mg QD
- The safety population included patients with ROS1+ NSCLC who received ≥1 dose(s) of taletrectinib 600 mg QD from Phase 1 and Phase 2 studies
Results
Patient Demographics and Baseline Characteristics
aAssessed by IRC per mRECIST v1.1.
Efficacy Summary
Data cutoff: October 28, 2024. aResponses were observed in 8/12 patients with G2032R mutations (ORR 66.7% [95% CI: 34.9–90.1]). bDOR reported in responders only. cAssessed by IRC per mRECIST v1.1 in patients with ≥1 measurable baseline brain metastasis.
TEAEs of Clinical Interest (N=349)
Data cutoff: October 28, 2024. aMedian time to onset for Grade ≥3 increased AST/ALT was 43 days (IQR: 22, 86) and median time to resolution was 13 days (IQR: 8, 19.5). These results are based on laboratory data.
- As of October 28, 2024, the integrated safety population included 349 patients with ROS1+ NSCLC from Phase 1 and Phase 2 studies
- The most common (any grade) TEAEs were increased AST, increased ALT, diarrhea, nausea, and vomiting (Supplement)
- With longer follow-up, TEAEs led to dose interruptions in 40.7% of patients, dose reductions in 28.9%, and treatment discontinuations in 7.2%
- The most common TEAEs leading to dose interruption or reduction were increased AST and ALT
- TEAEs of clinical interest were mostly low grade and transient, with low rates of dose modifications
TRUST-I and TRUST-II: DOR and PFS Were Similar Regardless of Dose Reduction Status9
Data cutoff: October 28, 2024.
Conclusions
- Taletrectinib demonstrated robust efficacy in both TKI-naïve and TKI-pretreated patients with advanced ROS1+ NSCLC
- With longer follow-up, taletrectinib maintained a manageable and consistent safety profile, with no new safety signals
- TEAEs of clinical interest, including increased AST/ALT, gastrointestinal events, and CNS events, were largely transient and low grade, and rarely led to treatment discontinuation
- Pooled analyses from the TRUST-I and TRUST-II studies demonstrated that dose reductions did not compromise efficacy
Supplement
TEAEs in ≥15% of Patients (N=349)a
Data cutoff: October 28, 2024. aThe safety population included patients with ROS1+ NSCLC who received ≥1 dose(s) of taletrectinib 600 mg QD from Phase 2 trials (TRUST-I and TRUST-II) and a Phase 1 trial (J102).
TRAEs in ≥15% of Patients (N=349)a
Data cutoff: October 28, 2024. aThe safety population included patients with ROS1+ NSCLC who received ≥1 dose(s) of taletrectinib 600 mg QD from Phase 2 trials (TRUST-I and TRUST-II) and a Phase 1 trial (J102).
Abbreviations
ALT, alanine aminotransferase; AST, aspartate aminotransferase; CI, confidence interval; CNS, central nervous system; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; IC, intracranial; IQR, interquartile range; IRC, independent review committee; (m)RECIST v1.1, (modified) Response Evaluation Criteria in Solid Tumors version 1.1; NA, not available; NR, not reached; NSCLC, non-small cell lung cancer; ORR, objective response rate; PFS, progression-free survival; QD, once daily; ROS1, ROS proto-oncogene 1; TEAE, treatment-emergent adverse event; TKI, tyrosine kinase inhibitor; TRAE, treatment-related adverse event.
References
- Katayama R, et al. Nat Commun 2019;10:3604
- Nagasaka M, et al. Future Oncol 2023;19:123–135
- IBTROZIⓇ (taletrectinib). Prescribing Information. Nuvation Bio Inc.; 2025
- Nippon Kayaku. Nippon Kayaku announces IBTROZIⓇCapsules 200mg (taletrectinib) has been approved in Japan for patients with unresectable advanced and/or recurrent ROS1-positive non-small cell lung cancer. Accessed January 20, 2026; https://www.nipponkayaku.co.jp/english/news/detail.php?n=20250919_6G5AI1Y7
- Nuvation Bio. Nuvation Bio receives approval from China’s National Medical Products Administration for taletrectinib for patients with advanced ROS1-positive non-small cell lung cancer. Accessed January 20, 2026; https://investors.nuvationbio.com/news/news-details/2025/Nuvation-Bio-Receives-Approval-from-Chinas-National-Medical-Products-Administration-for-Taletrectinib-for-Patients-with-Advanced-ROS1-positive-Non-Small-Cell-Lung-Cancer
- Pérol M, et al. J Clin Oncol 2025;43:1920–1929
- Li W, et al. J Thorac Oncol 2025;20(Suppl 1):S500
- Liu G, et al. J Thorac Oncol 2025;20(Suppl 1):S56
- Pérol M, et al. J Clin Oncol 2025;43(16_suppl):8643
Acknowledgments
We would like to thank all patients who participated in these studies, the study investigators, and their staff. These studies were sponsored by Nuvation Bio Inc. Medical writing support was provided by Lisa Alberts, MPhil, of Ashfield MedComms, an Inizio company, and was funded by Nuvation Bio Inc.
