Dr Sabari on Efficacy of Zidesamtinib in TKI-Pretreated, Advanced, ROS1+ NSCLC

“In all-comers, we saw a 44% ORR, 31 out of 71 patients with a response, including 2 complete responses. What was most interesting is that in those patients who had [received] prior repotrectinib, [we saw an ORR of] 38%.”

Joshua K. Sabari, MD, an assistant professor in the Department of Medicine at the NYU Grossman School of Medicine; as well as the director of High Reliability Organization Initiatives at the NYU Perlmutter Cancer Center, discussed key efficacy data from the phase 1/2 ARROS-1 trial (NCT05118789), which is investigating the selective ROS1 inhibitor zidesamtinib (NVL-520) in patients with advanced ROS1-positive non–small cell lung cancer (NSCLC).

Findings presented at the 2024 ESMO Congress showed that in all-comers in the TKI-pretreated population (n = 71), the overall response rate (ORR) was 44%, including 2 complete responses. Among patients who had received prior repotrectinib (Augtyro) and had a ROS1 G2032R mutation (n = 8), the ORR was 38%. Among patients who had not received prior repotrectinib and had a ROS1 G2032R mutation (n = 18), the ORR was 72%.

In the population of all-comers who had received at least 2 prior ROS1 TKIs (n = 51), the ORR was 41%. This rate was 47% in repotrectinib-naive patients who had received 2 or more prior ROS1 TKIs (n = 36). Additionally, among patients who had received 1 prior ROS1 TKI (n = 11)—crizotinib (Xalkori), the ORR was 73%.

These responses were also durable, Sabari explained. In the all-comer population, the median duration of response was not reached (NR; 95% CI, 10.3 months-NR).

Regarding the central nervous system (CNS) activity of zidesamtinib, the intracranial ORR was 50% among evaluable all-comers (n = 8). Historically, other ROS1 TKIs like crizotinib and entrectinib (Rozlytrek) have not demonstrated effective CNS penetration in patients with NSCLC, according to Sabari. However, next-generation ROS1 TKIs—including taletrectinib (Ibtrozi), repotrectinib, and now zidesamtinib—have shown effective levels of intracranial activity, Sabari concluded.