Dr Drilon on the Potential Benefit of Taletrectinib in ROS1+ NSCLC

Alexander Drilon, MD, thoracic oncologist, chief, early drug development service, Memorial Sloan Kettering Cancer Center, discusses the potential benefit of taletrectinib (AB-106) in patients with ROS1-positive non–small cell lung cancer (NSCLC).

Repotrectinib (Augtyro) is currently one of the only FDA-approved drugs for patients who are refractory to prior ROS1 TKIs. This approval was granted in November 2023 based on findings from the phase 1/2 TRIDENT-1 study (NCT03093116). However, repotrectinib is not the only next-generation ROS1 inhibitor that is being evaluated for this patient population, Drilon begins. 

The next-generation TKI taletrectinib has shown efficacy in patients post progression on a previous ROS1 TKI, he states. The agent is currently being investigated in the international, multicenter, open-label, single-arm, phase 2 TRUST-II trial (NCT04919811). Findings from this trial presented at the 2023 ESMO Congress demonstrated robust and durable tumor responses with taletrectinib in evaluable patients with ROS1-mutated NSCLC. The agent produced a confirmed overall response rate of 92.0% (95% CI, 74.0%-99.0%) in patients who were ROS1 TKI naive, and 57.1% (95% CI, 34.0%-78.2%) in those who were pretreated with a ROS1 TKI.

Beyond taletrectinib, the novel ROS1 inhibitor NVL-520 has also shown early benefit for patients within this patient population, Drilon adds.

The body of evidence in support of taletrectinib, including previously reported findings from the TRUST-I study (NCT04395677) in China, has expanded with data from TRUST-II, he states. Drilon explains that the agent may receive regulatory approval for both ROS1 TKI-pretreated and ROS1 TKI-naive patients. Notably, taletrectinib has shown clinical proof of principle, emphasizing its role as an active drug in this treatment space, he states.

Overall, the treatment armamentarium for patients with ROS1-positive NSCLC reflects the increased focus on precision medicine, Drilon continues. This paradigm extends beyond TKIs and small molecules to novel antibody-drug conjugates, he says. This diversified armamentarium may provide patients with innovative treatment options, Drilon explains.