Dr Bazhenova on Updated Data From the TRUST-I Trial of Taletrectinib in ROS1+ NSCLC

Lyudmila A. Bazhenova, MD, clinical professor, medicine, The University of California, San Diego (UCSD); medical oncologist, Moores Cancer Center, UCSD Health, discusses updated efficacy data from the phase 2 TRUST-I study (NCT04395677) investigating taletrectinib (AB-106) in patients with ROS1-positive advanced or metastatic non–small cell lung cancer (NSCLC) and highlights the agent's potential role in the NSCLC treatment paradigm.

The multicenter, single-arm, open-label, pivotal TRUST-I trial evaluated taletrectinib and was conducted in China. TRUST-I comprised both a cohort of patients who were TKI-naive and a cohort of patients pretreated with crizotinib (Xalkori). Findings from a larger patient sample were presented at the 2024 ASCO Annual Meeting, and they were found to be consistent with previously reported data, Bazhenova reports. With longer follow-up, taletrectinib demonstrated durable overall responses; robust intracranial and ROS1 G2032R activity; and a safety profile with a low incidence of neurologic adverse effects (AEs), she says.

In the TKI-naive cohort (n = 106), the overall response rate (ORR) was 90.6% (95% CI, 83.33%-95.38%) per independent central review assessment. Notably, the median progression-free survival (PFS) was not yet reached (NR; 95% CI, 29.1-NR) at a median follow-up of 23.5 months; the 2-year PFS rate was 70.5%. The PFS data were particularly impressive considering the aggressive nature of the disease, Bazhenova says.

In the crizotinib-pretreated cohort (n = 66), the ORR was 51.5% (95% CI, 38.88%-64.01%), and at a median follow-up of 9.7 months, the median PFS was 7.6 months (95% CI, 5.5-12.0). This cohort highlighted taletrectinib's efficacy against the ROS1 G2032R mutation—the most common resistance mutation to other ROS1-targeted TKIs, Bazhenova explains. For patients with this mutation (n = 12), the ORR was 66.7%.

Moreover, the data underscored the central nervous system (CNS) efficacy of taletrectinib, Bazhenova notes. Among patients with measurable CNS lesions, the intracranial confirmed ORR was 87.5% (95% CI, 47.35%-99.68%) in the TKI-naive cohort (n = 8) and 73.3% (95% CI, 44.90%-92.21%) in the crizotinib-pretreated cohort (n = 15).

Given these results, taletrectinib may be positioned for use as the first ROS1-targeted TKI and in the post-TKI setting, Bazhenova says. In TKI-naive patients, the ORR and durability of responses make the agent a strong candidate for patients who have not been exposed to a TKI. In the post-TKI setting, taletrectinib’s efficacy against resistant mutations such as ROS1 G2032R offers a valuable treatment option for patients who have progressed on other therapies, she explains.

However, taletrectinib's optimal role will be clearer after a full analysis of the data, Bazhenova adds. Regulatory agencies may require head-to-head clinical trials against currently approved standard-of-care treatments to make informed decisions about its approval and use. Until then, taletrectinib remains a TKI of interest with substantial potential to improve outcomes for patients with ROS1-positive NSCLC, Bazhenova concludes.