Key Takeaways
- FDA Approves Ibtrozi for ROS1+ NSCLC: Ibtrozi (taletrectinib) has been approved for adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC), based on strong results from the TRUST-I and TRUST-II trials.
- Up to 90% Response Rate in TKI-Naïve Patients: Clinical data showed confirmed overall response rates of up to 90% in treatment-naïve patients, with durable responses and significant intracranial activity.
- Well-Tolerated with Manageable Adverse Effects: Ibtrozi demonstrated a favorable safety profile, with most adverse events being mild and transient, making it a promising new targeted therapy option.
The FDA has approved Nuvation Bio’s Ibtrozi (taletrectinib), a next-generation oral ROS1 tyrosine kinase inhibitor (TKI), for the treatment of adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC). The approval was based on results from the Phase II TRUST-I and TRUST-II trials, which showed notable confirmed overall response rates (cORR) in treatment-naïve patients and demonstrated strong intracranial activity.1
How Does Ibtrozi’s Approval Advance Treatment for ROS1-Positive Lung Cancer?
“The FDA approval of Ibtrozi marks a major milestone in the evolution of targeted therapy for advanced ROS1-positive NSCLC,” said David Hung, MD, founder, president, CEO, Nuvation Bio, in a press release. “We believe one of the greatest threats to ROS1-positive lung cancer patients is disease progression, especially in the first line setting. In pivotal trials, Ibrtozi delivered high response rates with sustained durability—truly meaningful benefits for patients. With its clinically proven efficacy and safety profile, we believe Ibrtozi has the potential to become a new standard for what targeted therapies can achieve in this type of lung cancer. With approvals for Ibtrozi now in the US and China, and additional global filings underway, we remain committed to delivering innovative therapies that help patients stay ahead of their disease.”
TRUST-I and TRUST-II Trial Design and Endpoints
- The single-arm, pivotal TRUST-I and TRUST-II trials evaluated Ibtrozi in 173 and 164 patients, respectively.
- The primary endpoint of both trials was cORR as assessed by an independent review committee.
- Key secondary endpoints included intracranial cORR, duration of response (DOR), progression-free survival, and safety.
Efficacy Results in TKI-Naïve and Pretreated Patients
- In TRUST-I Ibtrozi demonstrated a cORR of 90% in TKI-naïve patients.
- In TRUST-II, Ibtrozi demonstrated an 85% cORR in TKI-naïve patients.
- Median DOR was not reached in TRUST-I, with the longest observed at 46.9 months and still ongoing.
- In TRUST-II, with a median follow up of 19 months, the longest DOR was observed at 30.4 months and ongoing.
- In patients treated with a ROS1 TKI, patients in TRUST-I demonstrated a cORR of 52% and median DOR of 13.2 months for TKI-pretreated patients, with a median follow up of 33 months.
- TRUST-II showed a cORR of 62%, with a median DOR of 19.4 months as of October 2024, and a median follow-up for responses of 19 months.
Safety and Tolerability Profile
- Common adverse events (AEs) included diarrhea; nausea; vomiting; dizziness; rash; constipation; and fatigue.
- Seven percent of patients discontinued treatment due to treatment-related AEs.
- Around 90% of reported dizziness cases were grade 1 and transient.
- The treatment was generally well tolerated.1
Stakeholder Perspectives and Broader Context
“For people living with advanced ROS1-positive lung cancer, who tend to be diagnosed at a younger age, having another treatment option can make a real difference for them and their loved ones,” said Janet Freeman-Daily, co-founder, president, The ROS1ders, in the press release. “The approval of this new targeted therapy is a meaningful step forward for the advanced ROS1+ lung cancer community and offers hope for patients facing the added challenge of cancer spreading to the brain.”
According to the American Cancer Society, NSCLC accounts for 87% of all lung cancers. Lung cancer as a whole is the second most common type of cancer for both men and women in the United States.2
“Patients living with advanced ROS1+ non-small cell lung cancer and their healthcare providers are in need of new treatment options,” said TRUST study investigator Nathan Pennell, MD, PhD, professor of medicine, Cleveland Clinic, in the press release. “Ibrtozi’s durability of response and ability to effectively penetrate the brain, coupled with a well-characterized and manageable safety profile, further addresses these critical needs for patients. I believe this now-approved therapy offers providers and patients a promising new option for the treatment of advanced ROS1+ non-small cell lung cancer.”
References
U.S. Food and Drug Administration Approves Nuvation Bio’s IBTROZI™ (taletrectinib), a Next-Generation Oral Treatment for Advanced ROS1-Positive Non-Small Cell Lung Cancer. Nuvation Bio. June 11, 2025. Accessed June 12, 2025. https://investors.nuvationbio.com/news/news-details/2025/U-S--Food-and-Drug-Administration-Approves-Nuvation-Bios-IBTROZI-taletrectinib-a-Next-Generation-Oral-Treatment-for-Advanced-ROS1-Positive-Non-Small-Cell-Lung-Cancer/default.aspx
Key Statistics for Lung Cancer. American Cancer Society. Accessed June 12, 2025. https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html
