Taletrectinib in TKI-Naïve Patients With ROS1+ NSCLC: Updated Data From TRUST-I and TRUST-II
Lyudmila Bazhenova,1 Jorge Nieva,2 Misako Nagasaka,3 Hidetoshi Hayashi,4 Qitao Yu,5 Scott Owen,6 Maurice Pérol,7 Feiwu Ran,8 Wei Wang,8 Xianyu Zhang,8 Wenfeng Chen,8 Wei Li,9 Geoffrey Liu,10 Caicun Zhou11
1UC San Diego Moores Cancer Center, 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; 4Kindai University Faculty of Medicine, Osaka, Japan; 5Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China; 6McGill University Health Centre, Montreal, QC, Canada; 7Léon Bérard Cancer Center, Lyon, France; 8Nuvation Bio Inc., New York, NY, USA; 9Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China; 10Princess Margaret Cancer Centre, Temerty School of Medicine, University of Toronto, Toronto, ON, Canada; 11Shanghai East Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China
Presented at the American Association for Cancer Research (AACR) Annual Meeting ⏐ April 17-22, 2026 ⏐ San Diego, CA, USA
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Background
- Taletrectinib is a next-generation, CNS-active, selective ROS1 TKI approved in the US, Japan, and China for the treatment of patients with locally advanced/metastatic ROS1+ NSCLC1–5
- Taletrectinib has shown robust efficacy, including intracranial activity, and a manageable safety profile in both TKI-naïve and TKI-pretreated patients with ROS1+ NSCLC in the Phase 2 TRUST-I (NCT04395677) and TRUST-II (NCT04919811) studies6–8
- Here we report updated efficacy data for taletrectinib in TKI-naïve patients from TRUST-I and TRUST-II, along with updated data from an integrated safety analysis
TRUST-I and TRUST-II: Pivotal Phase 2 Trials of Taletrectinib in ROS1+ NSCLC
aOr ≥20 years in TRUST-II, as required by local regulations. bRegistrational cohorts. cPatients who received one prior TKI. dThree TKI-naïve patients from TRUST-I started treatment on taletrectinib 400 mg QD as part of the lead-in stage, two of whom escalated to 600 mg QD.
- The efficacy population reported here included TKI-naïve patients from TRUST-I and TRUST-II with ≥1 measurable baseline lesion per RECIST v1.1 by IRC who started treatment on taletrectinib 600 mg QD
- Safety was evaluated in TKI-naïve and TKI-pretreated patients with ROS1+ NSCLC from Phase 1 and Phase 2 trials who received ≥1 dose of taletrectinib 600 mg QD
Baseline Characteristics
aIncludes three patients who started treatment on taletrectinib 400 mg QD. bIncludes patients with ≥1 measurable baseline lesion per RECIST v1.1 by IRC who started treatment on taletrectinib 600 mg QD (103 patients from TRUST-I and 54 patients from TRUST-II). cIncludes TKI-naïve and TKI-pretreated patients with ROS1+ NSCLC from Phase 1 and 2 trials who received ≥1 dose of taletrectinib 600 mg QD. dAssessed by IRC per mRECIST v1.1.
Tumor Response in TKI-Naïve Patients
Data cutoff: August 31, 2025
aPatients with ≥1 measurable baseline lesion per RECIST v1.1 by IRC who started treatment on taletrectinib 600 mg QD. bAssessed by IRC per mRECIST v1.1 in patients with ≥1 measurable baseline brain metastasis. Among these, three patients from TRUST-II had been previously treated with IC radiotherapy. cThree patients with cBOR of NE are not shown in the figure. One patient with cBOR of SD had
a best % change of 0%.
DOR in TKI-Naïve Patients From the Pooled Efficacy Analysis
Data cutoff: August 31, 2025
aDOR reported only for patients with a complete or partial tumor response.
DOR in TKI-Naïve Patients From TRUST-I and TRUST-II
Data cutoff: August 31, 2025
aDOR reported only for patients with a complete or partial tumor response.
PFS in TKI-Naïve Patients From the Pooled Efficacy Analysis
Data cutoff: August 31, 2025
PFS in TKI-Naïve Patients From TRUST-I and TRUST-II
Data cutoff: August 31, 2025
OS in TKI-Naïve Patients
Data cutoff: August 31, 2025
Median OS was NR (95% CI: 41.6–NR) for TRUST-I and NR (95% CI: NR–NR) for TRUST-II
Taletrectinib Safety Profile in the Integrated Safety Analysis (N=363)a
- With longer follow-up, no new safety signals were identified, and safety was consistent between the integrated safety populationa and TKI-naïve patients
- The most common (any grade) TEAEs were increased AST, increased ALT, diarrhea, nausea, and vomiting
- Rates of neurologic TEAEs were low and mostly Grade 1 or 2
- Dizziness: 18.5% Grade 1; 2.8% Grade 2
- Dysgeusia: 13.2% Grade 1; 2.2% Grade 2
- TEAEs led to dose interruptions in 42.7% of patients, dose reductions in 31.3%, and treatment discontinuations in 8.5%
Data cutoff: August 31, 2025
aThe integrated safety population includes TKI-naïve and TKI-pretreated patients with ROS1+ NSCLC who received ≥1 dose of taletrectinib 600 mg QD from Phase 2 trials (TRUST-I and TRUST-II) and a Phase 1 trial (J102).
Conclusions
- With ~3 years of follow-up in the pooled analysis and >4 years of follow-up in TRUST-I, taletrectinib demonstrated high and durable response rates in TKI-naïve patients with ROS1+ NSCLC, with a median DOR of >4 years
- To the best of our knowledge, these results represent the highest ORR and longest DOR and PFS reported to date for an FDA-approved ROS1 TKI in this patient population9–11
- With 10 months of additional follow-up since the last report, taletrectinib continued to demonstrate a manageable safety profile, with low rates of neurologic AEs and no new safety signals
- These data support taletrectinib as an effective, durable, and tolerable treatment option for patients with advanced ROS1+ NSCLC who have not received a prior ROS1 TKI
Abbreviations
AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BOR, best overall response; c, confirmed; CI, confidence interval; CNS, central nervous system; CR, complete response; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; FDA, US Food and Drug Adminstration; IC, intracranial; IRC, independent review committee; (m)RECIST v1.1, (modified) Response Evaluation Criteria in Solid Tumors version 1.1; NA, not available; NE, not evaluable; NR, not reached; NSCLC, non-small cell lung cancer; ORR, objective response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; QD, once daily; ROS1, ROS proto-oncogene 1; SD, stable disease; TEAE, treatment-emergent adverse event; TKI, tyrosine kinase inhibitor; US, United States.
References
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- Nagasaka M, et al. Future Oncol 2023;19:123–135.
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- Nippon Kayaku. IBTROZI® Capsules 200mg (taletrectinib) has been approved in Japan. Accessed February 26, 2026; https://www.nipponkayaku.co.jp/english/news/detail.php?n=20250919_6G5AI1Y7.
- Nuvation Bio. Nuvation Bio Receives Approval from China’s NMPA for Taletrectinib. Accessed February 26, 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.
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- Li W, et al. J Thorac Oncol 2025;20(Suppl 1):S500.
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- Shaw AT, et al. Ann Oncol 2019;30:1121–1126.
- Drilon A, et al. N Engl J Med 2024;390:118–131.
- Fan Y, et al. Clin Lung Cancer 2024;25:e81–e86.
Acknowledgments
- We would like to thank all patients who participated in these studies, the study investigators, and their staff
- The 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.
Disclosure Information
Lyudmila Bazhenova, MD
I declare the following potential conflicts of interest:
- Independent contractor for: AbbVie, AnHeart Therapeutics, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Genentech, Johnson & Johnson, Merck, Natera, Nuvalent, Pfizer, Revolution Medicines, Summit, and Taiho Oncology
