Nuvation Bio's taletrectinib, a next-generation ROS1 tyrosine kinase inhibitor (TKI), has shown promising results in patients with advanced ROS1-positive non-small cell lung cancer (NSCLC). Pooled data from the pivotal Phase 2 TRUST-I and TRUST-II studies, presented at the European Society of Medical Oncology (ESMO) Congress 2024, highlight the drug's potential as a best-in-class treatment option. The data supports Nuvation Bio's plan to submit a New Drug Application (NDA) to the U.S. FDA in the fourth quarter of 2024.
Significant Tumor Shrinkage and Durability
The pooled efficacy analyses included 160 TKI-naïve patients and 113 TKI-pretreated patients. Key findings include:
- In TKI-naïve patients, taletrectinib achieved an 89% confirmed objective response rate (cORR), indicating significant tumor shrinkage.
- Measurable brain metastases shrank in 77% (13/17) of TKI-naïve patients, demonstrating intracranial efficacy.
- Median duration of response (DOR) and progression-free survival (PFS) in TKI-naïve patients were 44 months and 46 months, respectively, after a median follow-up of 21 months.
- In TKI-pretreated patients, the cORR was 56%, and intracranial cORR was 66% (21/32).
- Tumors shrank in 62% (8/13) of TKI-pretreated patients with G2032R mutations.
Maurice Perol, M.D., TRUST-II study investigator and Head of Thoracic Oncology at Léon Bérard Cancer Center, noted the critical unmet need for more effective and tolerable treatments for patients with advanced ROS1-positive NSCLC, emphasizing taletrectinib’s potential to offer clinically meaningful advancements in efficacy combined with a favorable safety profile.
Favorable Safety Profile
The pooled safety analysis, which included 337 patients, demonstrated a favorable safety and tolerability profile. The incidence of neurologic treatment-emergent adverse events (TEAEs) was low, with dizziness (21%) and dysgeusia (15%) being the most common, mostly Grade 1. The rate of treatment discontinuation due to TEAEs was 7%, and the rate of dose reduction due to TEAEs was 29%. Common TEAEs included increased aspartate aminotransferase (72%; 8% ≥ Grade 3) and alanine aminotransferase (68%; 10% ≥ Grade 3), diarrhea (63%; 2% ≥ Grade 3), and nausea (47%; 2% ≥ Grade 3).
Implications for ROS1-Positive NSCLC Treatment
These results position taletrectinib as a promising treatment option for patients with ROS1-positive NSCLC, a subset affecting approximately 2% of NSCLC cases. The drug's efficacy in both TKI-naïve and TKI-pretreated patients, including those with brain metastases and G2032R mutations, addresses critical unmet needs in this patient population. The favorable safety profile suggests that taletrectinib may offer a better balance of efficacy and tolerability compared to existing ROS1 inhibitors.
David Hung, M.D., Founder, President, and Chief Executive Officer of Nuvation Bio, expressed excitement about the compelling data, highlighting taletrectinib’s durable response, prolonged disease control, and favorable safety profile. He believes these results position taletrectinib as a potential best-in-class treatment option for people living with advanced ROS1-positive NSCLC.
Regulatory and Commercialization Plans
Nuvation Bio plans to submit an NDA to the FDA in the fourth quarter of 2024, with a potential U.S. launch in 2025. Taletrectinib has already been granted Orphan Drug Designation by the U.S. FDA and Breakthrough Therapy Designations by both the U.S. FDA and China’s National Medical Products Administration (NMPA).
