The trial is evaluating the safety and efficacy of taletrectinib in ROS1 NSCLC. Taletrectinib is a novel TKI.
The first patient has been dosed in the phase 2 TRUST-II study of taletrectinib (DS-6051b/AB-106) in patients with ROS1-fusion-positive lung cancer, according to a press release by AnHeart Therapeutics.1
Taletrectinib is an investigational next-generation tyrosine kinase inhibitor that is meant to target by ROS1 and NTRK fusion mutations. It has the potential to treat by TKI-naïve or TKI-pretreated patients. A ROS1 mutation is an oncogenic driver in an estimated 2% to 3% of all advanced NSCLC patients.
The TRUST-II study (NCT04919811) has an estimated enrollment of 119 patients with an estimated study completion date of June 2027. The primary end point of the study is objective response rate (ORR). Secondary end points include progression-free survival (PFS), efficacy, safety and tolerability, and the pharmacokinetic profile. Other outcomes measured include intracranial PFS and intracranial ORR.2
During the single-arm study, all patients will receive 600 mg of taletrectinib once daily in 21-day cycles.
Preliminary results from the phase 2 TRUST study (NCT04395677) showed that crizotinib treatment-naïve patients with ROS1 fusion NSCLC (n=15) had an ORR of 93% following treatment with taletrectinib. In pretreated patients (n=5), the ORR was 60% and the disease control rate was 100%. Adverse events were manageable, and largely gastrointestinal in nature.3
In order to participate in the study, patients must be 18 years of age or older, have a confirmed diagnosis of locally advanced or metastatic NSCLC or other solid tumor, have evidence of a ROS1 fusion in tumor tissue, be ROS1 TKI naive, have at least one measurable lesion, and ECOG score of 0 or 1, a life expectancy of 12 weeks or more, and adequate organ function.
Patients who have received an investigational agent or anticancer therapy within 2 weeks to study enrollment, major surgery within 4 weeks of study enrollment, unresolved prior toxicities, spinal cord compression, or evidence of a viral infection are not eligible to participate.
"Taletrectinib dosing of the first patient in our global Phase 2 ROS1 fusion-positive TRUST-II lung cancer trial represents a key milestone for our lead ROS1-directed clinical program," said Bing Yan, MD, co-founder and chief medical officer of AnHeart Therapeutics, in a press release. "Based on the broad expression of ROS1 fusions across different cancer types, and our recent clinical data presented at ASCO and CSCO showing taletrectinib antitumor activity with a promising safety and efficacy profile, we are proud of advancing this investigational candidate as a potential new therapy for ROS1 fusion-positive lung cancer."