NCCN Guidelines Recommend Taletrectinib for ROS1+ NSCLC Subtype

The NCCN Clinical Practice Guidelines in Oncology for Central Nervous System (CNS) cancers now includes taletrectinib (Ibtrozi) as a recommended systemic therapy option for patients with ROS1-positive NSCLC harboring brain metastases, according to a press release from the developer, Nuvation Bio Inc.^1,2

The latest guidelines, updated on April 24, 2026, indicate taletrectinib as a suitable treatment option for patients with NSCLC harboring a positive ROS1 gene fusion alongside repotrectinib (Augtyro). Of note, the NCCN previously added taletrectinib as a preferred agent in the frontline setting and beyond for patients with ROS1-positive NSCLC in its Clinical Practice Guidelines in Oncology for NSCLC in June 2025.

“We are encouraged to see taletrectinib added to the NCCN Guidelines for CNS Cancers given its demonstrated high rates of [durable] intracranial response in [patients with ROS1-positive] NSCLC with brain metastases. Given the prevalence of CNS tumors among [patients with ROS1-positive] NSCLC, taletrectinib can address a critical need for these patients, offering meaningful brain penetrance while maintaining a favorable neurologic safety profile,” David Hung, MD, founder, president, and chief executive officer of Nuvation Bio, said in the press release.² “Additionally, with this update, taletrectinib is now one of the few therapies to be added by NCCN to both NSCLC and CNS guidelines.”

The FDA previously approved taletrectinib for patients with locally advanced or metastatic ROS1-positive NSCLC in June 2025.³ Supporting findings for the approval came from the phase 2 TRUST-I trial (NCT04395677) and the phase 2 TRUST-II trial (NCT04919811). Updated long-term findings from the TRUST-I and TRUST-II trials were presented at the 2026 American Association for Cancer Research (AACR) Annual Meeting.⁴

In a pooled population of 157 patients who received no prior tyrosine kinase inhibitors (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. The intracranial response rate was 76.5% among 17 patients with evaluable brain metastases. Additionally, the median overall survival (OS) was not reached in this cohort.

Among 113 patients who received prior TKIs, taletrectinib produced a confirmed ORR of 55.8%, a median DOR of 16.6 months, and a median PFS of 9.7 months. The intracranial response rate was 65.6% among 32 patients with evaluable brain metastases in this group. Data also showed a median OS of 29.8 months.

Pooled data showed that the safety profile of taletrectinib in the TRUST-I and TRUST-II trials was comparable with its prescribing information. The most common adverse effects (AEs) included diarrhea, nausea, vomiting, and dizziness, which typically occurred at low grades and resolved quickly. Additionally, 8.5% of patients discontinued taletrectinib due to treatment-emergent AEs. Investigators reported no new safety signals after longer follow-up.

“[T]aletrectinib 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 a professor of medicine at UC San Diego Moores Cancer Center, stated in an interview with CancerNetwork^® regarding updated findings from the TRUST-I and TRUST-II trials.

Across the studies, the primary end points included best overall response per independent review committee evaluation in TRUST-I and ORR per independent radiology review using RECIST v1.1 criteria in TRUST-II.^5,6 Secondary end points across both trials included AEs, PFS, intracranial responses and pharmacokinetics.

According to the press release, the placebo-controlled phase 3 TRUST-IV trial (NCT07154706) will assess adjuvant taletrectinib among approximately 180 patients with resected early-stage ROS1-positive NSCLC.

References

1. NCCN. Clinical Practice Guidelines in Oncology. Central Nervous System Cancers, version 1.2026. Accessed April 28, 2026. https://tinyurl.com/ywfaxkne
2. Nuvation Bio announces National Comprehensive Cancer Network® adds taletrectinib (IBTROZI®) as recommended option to clinical practice guidelines in oncology for central nervous system cancers. News release. Nuvation Bio Inc. April 27, 2026. Accessed April 28, 2026. https://tinyurl.com/2prfcwym
3. FDA approves taletrectinib for ROS1-positive non-small cell lung cancer. News release. FDA. June 11, 2025. Accessed April 28, 2026. https://tinyurl.com/yc4f379m
4. 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 April 28, 2026. https://tinyurl.com/47s5w3y7
5. A study of AB-106 in subjects with advanced NSCLC harboring ROS1 fusion gene. ClinicalTrials.gov. Updated February 6, 2026. Accessed April 28, 2026. https://tinyurl.com/44wfyjxh
6. Taletrectinib phase 2 global study in ROS1 positive NSCLC (TRUST-II). ClinicalTrials.gov. Updated January 7, 2026. Accessed April 28, 2026. https://tinyurl.com/4r7x8hp2