Taletrectinib Extends Cancer-Free Time With Fewer Neurological Side Effects in NSCLC Patients

Nuvation Bio announced promising pooled data from the TRUST-I and TRUST-II studies for taletrectinib, a next-generation ROS1 tyrosine kinase inhibitor (TKI) designed for patients with advanced ROS1-positive non-small cell lung cancer (NSCLC).

With around two percent of NSCLC cases being ROS1-positive, and up to 55 percent of patients experiencing disease progression to the brain, there is a need for better treatments.

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The studies, presented at the European Society of Medical Oncology (ESMO) Congress, highlighted significant tumor shrinkage and extended progression-free survival (PFS) in patients, reinforcing taletrectinib’s potential as a leading treatment for ROS1-positive NSCLC. Results from the Phase II TRUST-I study, published in the Journal of Clinical Oncology, have been key in advancing taletrectinib’s clinical profile.

The TRUST-I study found that taletrectinib demonstrated a higher overall response rate in both TKI-naïve patients (90.6 percent) and patients pretreated with Pfizer’s crizotinib (51.5 percent), with fewer severe neurological side effects, adding to its clinical appeal.

In the pooled analysis, tumor shrinkage occurred in 89 percent of the 160 TKI-naïve patients, while 56 percent of TKI-pretreated patients also saw significant tumor reduction. Impressively, TKI-naïve patients showed a median duration of response (DOR) of 44 months and progression-free survival (PFS) of 46 months.

Among those who had already undergone prior treatments, the median DOR stood at 17 months, with a PFS of 10 months. Additionally, patients with measurable brain metastases responded well to treatment — 77 percent of TKI-naïve patients and 66 percent of TKI-pretreated patients saw confirmed brain tumor shrinkage.

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Taletrectinib’s favorable safety profile was another key highlight. The most common side effects included elevated liver enzymes, diarrhea and nausea. Severe neurologic adverse events remained low. Dizziness and taste alterations were reported, though most were mild. Treatment discontinuations due to side effects were seen in seven percent of patients.

Nuvation Bio’s efforts to establish taletrectinib as a best-in-class therapy are ongoing. With the ongoing TRUST-I and TRUST-II studies, taletrectinib could offer a much-needed option for patients with ROS1-positive NSCLC, particularly those with limited treatment alternatives.

Assuming regulatory approval, taletrectinib may launch in the US by 2025, marking a significant advancement in the treatment landscape for ROS1-positive NSCLC.