Nuvation Bio's Phase 2 TRUST-I Data on Taletrectinib Published in JCO and Presented at 2024 ASCO

Nuvation Bio Inc., a biopharmaceutical company in the late stages of clinical development, recently announced promising results from their pivotal Phase 2 TRUST-I study of taletrectinib. Published in the Journal of Clinical Oncology, the findings will also be highlighted in an oral presentation at the 2024 American Society of Clinical Oncology Annual Meeting. The study evaluates taletrectinib, an investigational next-generation ROS1 tyrosine kinase inhibitor (TKI), in treating advanced ROS1-positive non-small cell lung cancer (NSCLC).

The study involved 173 patients with advanced ROS1-positive NSCLC. Among these patients, 106 had not been treated previously with a ROS1 TKI (TKI-naïve), while 66 had been treated with crizotinib (TKI-pretreated). Tumors shrank in 91% of TKI-naïve patients and 52% of TKI-pretreated patients. Furthermore, taletrectinib proved effective in treating disease spread to the brain and in patients with acquired resistance mutations, including the G2032R mutation.

Data from the study indicate that taletrectinib exhibits durable responses, especially in TKI-naïve patients. After a median follow-up of 23.5 months, the median duration of response and progression-free survival had not been reached. In contrast, TKI-pretreated patients showed a median duration of response of 10.6 months and median progression-free survival of 7.6 months after a 9.7-month follow-up. The safety profile of taletrectinib was consistent with previous reports, showing a low incidence of neurologic adverse events.

Dr. Caicun Zhou, the principal investigator of the TRUST-I study, remarked on the significance of these findings, noting the necessity for new treatment options for advanced ROS1-positive NSCLC that are both well-tolerated and offer enduring responses. David Hung, M.D., Founder, President, and CEO of Nuvation Bio, emphasized the consistency of the new data with prior results and the potential of taletrectinib to become a best-in-class treatment option. Nuvation Bio plans to share results from the global TRUST-II study by the end of 2024 and aims to become a commercial-stage organization by the end of 2025.

The TRUST-I study is a multicenter, single-arm, open-label study evaluating taletrectinib as a monotherapy. Patients received 600 mg of taletrectinib orally once daily in 21-day treatment cycles. The primary endpoint was the confirmed objective response rate (cORR), and secondary endpoints included duration of response, progression-free survival, and safety.

Results showed a 90.6% cORR in TKI-naïve patients, with 87.5% of patients with measurable brain tumors showing tumor shrinkage. At the two-year mark, 78.6% of responders were still responding, and 70.5% were progression-free. In TKI-pretreated patients, the cORR was 51.5%, with 73.3% of those with brain tumors experiencing shrinkage. Additionally, 66.7% of patients with G2032R mutations saw tumor shrinkage. At nine months, 69.8% of responders were still responding, and 47.4% were progression-free.

The most common treatment-emergent adverse events (TEAEs) included increased liver enzymes, diarrhea, vomiting, and anemia, most of which were mild to moderate in severity. Neurologic TEAEs were infrequent and mostly mild, with dizziness being the most common. Discontinuations and dose reductions due to TEAEs were minimal.

Taletrectinib is a next-generation ROS1 inhibitor designed for patients with advanced ROS1-positive NSCLC. It has received Breakthrough Therapy Designations from both the U.S. FDA and China’s NMPA. The TRUST-I study’s results have led to the acceptance and priority review of New Drug Applications for taletrectinib in China.

Nuvation Bio, founded in 2018, is focused on addressing unmet needs in oncology through innovative therapeutic candidates. Their portfolio includes several promising drugs currently in development.