Taletrectinib Sustains Positive Efficacy and Safety in ROS1-Positive NSCLC

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Taletrectinib (DS-6051b/AB-106) continued to demonstrate clinically meaningful efficacy and favorable a safety profile in patients with ROS1-positive non–small cell lung cancer (NSCLC), according to updated efficacy and safety data from the phase 2 TRUST-I trial (NCT04395677).¹

In an oral presentation at the European Lung Cancer Congress (ELCC) 2023, experts reported that at about 1.5-year follow-up time, the confirmed objective response rate (ORR) was 92.5% among patients who were ROS1 tyrosine kinase inhibitor (TKI)-naïve, and 52.6% in crizotinib (Xalkori)-pretreated patients. The intracranial ORR was 91.7%, regardless of prior ROS1 TKI treatment history, and the ORR among patients with a ROS1 G2032R resistance mutation was 80.0%.

Taletrectinib, a potent, next-generation, central nervous system-active ROS1 TKI. Previously, the FDA granted the agent a breakthrough therapy designation for the treatment of patients with advanced or metastatic ROS1-positive NSCLC, who are either ROS1 TKI treatment naïve or who were previously treated with crizotinib.

In the multicenter, open-label, single-arm TRUST-I trial, investigators assessed treatment with taletrectinib in 2 cohorts. The first cohort consisted of patients who were ROS1 TKI-naïve while the second included patients who were pretreated with crizotinib.² The goals of the study were to evaluate safety, pharmacokinetics (PK), and efficacy taletrectinib for patients with advanced NSCLC.

Part 1 of the trial sought to determine the safety and PK profile of the agent using 2 doses of taletrectinib at 400 mg and 600 mg every day. This portion of the trial confirmed 600 mg daily as the optimal dose. Then, part 2 evaluated the efficacy and safety of taletrectinib using the optimal dose of 600 mg daily

Patients enrolled in the trial must have been aged 18 years or older with histologically or cytologically confirmed locally advanced or metastatic NSCLC that is positive for an ROS1 fusion as determined by the local qualified laboratories using the FISH, RT-PCR or NGS assay. For cohort A, patients must be TKI treatment naïve and patients in cohort B must have had disease progression following treatment with crizotinib. Additionally, patients with brain metastases must have been asymptomatic or neurologically stable for at least 2 weeks prior to study entry, have at least 1 measurable target tumor lesion, an ECOG performance status of 0 or 1, a life expectancy ≥ 3 months, and adequate organ function. Prior therapies, including chemotherapies, radiotherapy, or surgery, should have been completed at least 2 weeks prior to study entry.

The primary study end point was best overall response with secondary end points including the number of patients with treatment-related adverse events, PK, duration of response, time to response, time to progression, progression-free survival, intracranial best overall response, duration of intracranial response, and overall survival.

Now, a pivotal, global, phase 2 trial, TRUST-II, (NCT04919811) is actively enrolling patients at clinical sites in North America, Europe, and Asia to further evaluate treatment with taletrectinib.¹

"We’re excited to see that, with longer follow-up time, taletrectinib continues to demonstrate robust efficacy outcomes and favorable safety profiles in patients with ROS1 TKI-naïve or crizotinib-pretreated ROS1-positive NSCLC," said Caicun Zhou, PhD, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China, in the press release. "Additionally, taletrectinib hits a unique balance of strong intracranial activity and low incidence of neurological [adverse events]."

REFERENCES

1. AnHeart therapeutics presents updated efficacy and safety of taletrectinib in patients with ROS1-positive non–small cell lung cancer. News release. AnHeart Therapeutics. March 31, 2023. Accessed April 7, 2023. https://yhoo.it/3mdK8ht

2. A study of AB-106 in subjects with advanced NSCLC harboring ROS1 fusion gene. ClinicalTrials.gov. Updated June 18, 2021. Accessed April 7, 2023. https://clinicaltrials.gov/ct2/show/NCT04395677