FDA Accepts sNDA for Taletrectinib in ROS1-Positive NSCLC

The FDA has accepted a supplemental new drug application (sNDA) for taletrectinib (Ibtrozi) for patients with advanced ROS1-positive non–small cell lung cancer (NSCLC) regardless of prior receipt of tyrosine kinase inhibitors (TKIs), according to a press release from the developer, Nuvation Bio Inc.¹ The regulatory agency has set a Prescription Drug User Fee Act date of January 4, 2027, for approving taletrectinib in this indication.

The sNDA is intended to fulfill a regulatory post-marketing commitment and update efficacy information noted in the taletrectinib label, which includes 10 additional months of data from the phase 2 TRUST-I (NCT04395677) and TRUST-II trials (NCT04919811). Updated findings from these studies were presented at the 2026 American Association for Cancer Research (AACR) Annual Meeting.²

In a pooled analysis of 157 patients with no prior receipt of TKIs, taletrectinib produced a confirmed overall response rate (ORR) of 89.8%, a median duration of response (DOR) of 49.7 months, and a median progression-free survival (PFS) of 46.1 months. Additionally, the agent yielded an intracranial response rate of 76.5% among 17 patients with brain metastases. The median overall survival (OS) was not yet reached at the time of analysis.

Among 113 patients who were previously treated with TKIs, taletrectinib demonstrated a confirmed ORR of 55.8%, a median DOR of 16.6 months, and a median PFS of 9.7 months. In 32 patients with evaluable brain metastases, investigators reported an intracranial response rate of 65.6%. The median OS was 29.8 months in this cohort.

Pooled data showed that taletrectinib demonstrated a favorable and manageable safety profile that was comparable with prior reports. Most adverse effects of clinical interest, including diarrhea, nausea, vomiting, and dizziness, occurred at low grades and resolved quickly. Additionally, 8.5% of patients discontinued study therapy due to treatment-emergent adverse effects. Overall, investigators observed no new safety signals.

“These longer-term data for [taletrectinib]—which show an impressive median [DOR] of more than 4 years in [patients who are] TKI naïve, mirrored by the [PFS] results and supported by a consistent safety profile—reinforce our belief that [taletrectinib] is becoming the new standard of care in advanced [ROS1-positive] NSCLC,” David Hung, MD, founder, president, and chief executive officer at Nuvation Bio, stated in the press release.¹ “The breadth and maturity of these data give both patients and providers even greater confidence when selecting [taletrectinib].”

The TRUST clinical program includes 3 registrational studies assessing the efficacy and safety of taletrectinib among patients with ROS1-positive NSCLC. The primary end point of the TRUST-I and TRUST-II studies was confirmed ORR per independent review committee evaluation.

Additionally, investigators will assess adjuvant therapy with taletrectinib among adult patients with resected early-stage ROS1-positive NSCLC in the phase 3 TRUST-IV study (NCT07154706). Approximately 180 patients across the US, Canada, Europe, Japan, and China will be assigned to receive taletrectinib or matched placebo. The trial’s primary end point will be disease-free survival.

The FDA approved taletrectinib for patients with locally advanced or metastatic ROS1-positive NSCLC based on prior results from the TRUST-I and TRUST-II trials in June 2025.³ Additionally, the NCCN Clinical Practice Guidelines in Oncology for Central Nervous System (CNS) Cancers added taletrectinib as a recommended systemic therapy option for patients with ROS1-positive NSCLC harboring brain metastases in April 2026.⁴

“Taletrectinib is a very effective oral [TKI] that should be considered for patients with ROS1-rearranged NSCLC,” study investigator Lyudmila Bazhenova, MD, FASCO, a board-certified medical oncologist and professor of medicine at the University of California San Diego Moores Cancer Center, stated in an interview with CancerNetwork^® about updated findings from the TRUST-I and TRUST-II trials.

References

1. Nuvation Bio announces FDA acceptance of supplemental new drug application for IBTROZI® (taletrectinib) with updated duration of response in advanced ROS1-positive non-small cell lung cancer. News release. Nuvation Bio Inc. May 6, 2026. Accessed May 7, 2026. https://tinyurl.com/ysava526
2. Nuvation Bio announces IBTROZI (taletrectinib) showed highly durable responses in longer-term follow-up data from pivotal studies presented at AACR 2026. News release. Nuvation Bio Inc. April 21, 2026. Accessed May 7, 2026. https://tinyurl.com/47s5w3y7
3. FDA approves taletrectinib for ROS1-positive non-small cell lung cancer. FDA. June 11, 2025. Accessed May 7, 2026. https://tinyurl.com/yc4f379m
4. NCCN. Clinical Practice Guidelines in Oncology. Central nervous system cancers, version 1.2026. Accessed May 7, 2026. https://tinyurl.com/ywfaxkne