Randomized, Double-Blind, Phase 3 TRUST-IV Study of Adjuvant Taletrectinib vs Placebo in Patients With Stage IB–IIIA ROS1+ Non-Small Cell Lung Cancer (NSCLC)
1Virginia Cancer Specialists and US Oncology, Fairfax, VA, USA; 2Memorial Sloan Kettering Cancer Center, New York, NY, USA; 3David Geffen School of Medicine, University of California, Los Angeles, CA, USA; 4Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; 5Thoraxklinik and National Center for Tumor Diseases at Heidelberg University Hospital, Heidelberg, Germany; 6Centre Léon Bérard, Lyon, France; 7Nuvation Bio Inc., New York, NY, USA; 8Princess Margaret Cancer Centre, Temerty School of Medicine, University of Toronto, Toronto, ON, Canada; 9Shanghai East Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China
Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting ⏐ May 29–June 2, 2026 ⏐ Chicago, IL, USA ⏐ For more information, please contact Dr Alexander Spira: Alexander.Spira@USOncology.comJump to a section:
Background & Rationale
- Taletrectinib is a next-generation, CNS-active, selective ROS1 TKI approved in the US, Japan, and China for the treatment of adult patients with locally advanced or metastatic ROS1+ NSCLC1–5
- A marketing authorization application for taletrectinib has been submitted to the European Medicines Agency and is currently under review6
- Taletrectinib has demonstrated durable and robust efficacy in both TKI-naïve and TKI-pretreated patients with advanced ROS1+ NSCLC;7,8 in TKI-naïve patients, cORR was 90%, with median DOR and median PFS exceeding 4 years after >4 years of follow-up9
- Taletrectinib has demonstrated a manageable safety profile, with AEs of clinical interest being mostly low grade and transient, and with a low rate of treatment discontinuations7–10
- Treatment for resectable stage IB–IIIA NSCLC typically includes complete surgical resection with perioperative platinum-based chemotherapy (neoadjuvant and/or adjuvant), with or without ICI therapy; however, disease recurrence is still common11
- Phase 3 trials have shown that, with some oncogenic drivers in early-stage NSCLC (e.g., EGFR mutations, ALK fusions), adjuvant targeted therapy can significantly improve DFS vs standard-of-care treatment12,13
- However, no adjuvant targeted therapies are currently approved for ROS1+ NSCLC, representing a clear unmet clinical need
- Given the demonstrated efficacy of taletrectinib in advanced ROS1+ NSCLC, evaluation in the adjuvant setting following complete resection is warranted
TRUST-IV Study Design
- TRUST-IV (NCT07154706) is a randomized, double-blind, multicenter, Phase 3 study evaluating the efficacy and safety of adjuvant taletrectinib in patients with completely resected stage IB–IIIA ROS1+ NSCLC
aSurgery performed ≥4 or ≤16 weeks before randomization if no adjuvant chemotherapy was given; ≥4 or ≤30 weeks if adjuvant chemotherapy was given. bAdjuvant ICI therapy is allowed, but patients should have received no more than four cycles of ICI, and at the time of randomization, have at least 12 weeks of washout from the last dose of ICI.
Trial Progress
- TRUST-IV (NCT07154706)14 is currently recruiting patients in the US, Canada, and China, with additional sites planned in other countries in 2026
- In the US, this study is included in the Tempus TIME program for rapid site activation
- First patient enrolled: September 30, 202515
- Estimated primary completion date: August 2030
- Estimated study completion date: August 2033
Summary
- TRUST-IV is a randomized, double-blind, multicenter, Phase 3 study evaluating the efficacy and safety of taletrectinib compared with placebo in patients with stage IB, II, or IIIA ROS1+ NSCLC following complete tumor resection
- The study is currently recruiting in the US, Canada, and China, with further global expansion in 2026
Abbreviations
AE, adverse event; AJCC, American Joint Committee on Cancer; ALK, anaplastic lymphoma kinase; BICR, blinded independent central review; c, confirmed; CNS, central nervous system; DFS, disease-free survival; DOR; duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; ICI, immune checkpoint inhibitor; INV, investigator; NSCLC, non-small cell lung cancer; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PK, pharmacokinetics; R, randomized; ROS1, ROS proto-oncogene 1; TKI, tyrosine kinase inhibitor; US, United States
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. IBTROZIⓇ Capsules 200mg (taletrectinib) has been approved in Japan. Accessed May 6, 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 May 6, 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
- Nuvation Bio. Eisai and Nuvation Bio Announce EMA Validation of Taletrectinib MAA for ROS1+ NSCLC. Accessed May 6, 2026; https://investors.nuvationbio.com/news/news-details/2026/Eisai-and-Nuvation-Bio-Announce-Marketing-Authorisation-Application-for-Taletrectinib-for-the-Treatment-of-Advanced-ROS1-Positive-Non-Small-Cell-Lung-Cancer-Validated-by-the-European-Medicines-Agency/default.aspx
- Bazhenova L, et al. Cancer Res 2026;86(8_Suppl):CT300
- Liu G, et al. Cancer Res 2026;86(8_Suppl):CT244
- Li W, et al. J Clin Oncol 2026. doi: 10.1200/JCO-26-00434 (online ahead of print)
- Elamin YY, et al. ESMO Open 2026;11(Suppl 3):53P
- Mirsky MM, et al. J Clin Med 2025;14:4127
- Wu Y-L, et al. N Engl J Med 2020;383:1711–1723
- Wu Y-L, et al. N Engl J Med 2024;390:1265–1276
- ClinicalTrials.gov. NCT07154706. Accessed May 6, 2026; https://clinicaltrials.gov/study/NCT07154706
- Nuvation Bio. First Patient Enrolled in Phase 3 TRUST-IV Study of Adjuvant Taletrectinib in ROS1+ Early-Stage NSCLC. Accessed May 6, 2026; https://investors.nuvationbio.com/news/news-details/2025/Nuvation-Bio-Enrolls-First-Patient-in-TRUST-IV-Phase-3-Study-of-IBTROZI-taletrectinib-for-the-Adjuvant-Treatment-of-ROS1-Positive-Early-Stage-Non-Small-Cell-Lung-Cancer/default.aspx
Acknowledgments
We would like to thank all patients who are participating in this ongoing study, the study investigators, and their staff. Prof. Caicun Zhou and Dr Geoffrey Liu serve as Co-Chairs of the steering committee for this trial. We also acknowledge the contributions to the study of Dih-Yih Chen and Xianyu Zhang from Nuvation Bio Inc. This study is 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.
