392P - A phase II study of SAF-189s in patients with advanced ROS1 fusion-positive non-small cell lung cancer

Background

ROS1 fusions (ROS1+) are enriched in 1-2% of non-small cell lung cancer (NSCLC) cases. SAF-189s is a novel, next-generation ALK/ROS1 inhibitor which overcomes multiple resistance mutations. We explored the efficacy and safety of SAF-189s in phase (Ph) 2 study in patients (pts) with ROS1 fusion NSCLC, with or without ROS1 inhibitor treatment.

Methods

This multicenter, single-arm, open-label, Ph2 study enrolled Chinese patients with advanced ROS1+ NSCLC. The study included 2 cohorts: ROS1 inhibitor (ROS1i)-naïve or crizotinib-pretreated pts in a Ph2a cohort receiving SAF-189s with dose escalation (80, 120, 160 and 210 mg doses QD), and ROS1i-naïve pts alone in a Ph2b cohort receiving 160 mg QD. The primary endpoint was Independent Review Committee (IRC)-assessed overall response rate (ORR).

Results

Between Dec 12, 2021 and Mar 25, 2022, 48 and 56 pts were enrolled in the Ph2a and 2b cohorts, respectively. IRC-confirmed ORR in ROS1i-naïve pts were 94.1% and 80.4% and DCR were 94.1% and 96.4% in pts in Ph2a and Ph2b respectively. Notably, confirmed ORRs and DCRs were similar in pts with and without brain metastasis (Table). Median PFS was 16.5 mo in Ph 2a and not reached in Ph 2b. In crizotinib-pretreated pts in Ph2a, confirmed ORR was 40% and median PFS was 5.5 mo. The majority of treatment-related adverse events (TRAEs) were grade 1 or 2. Grade ≥3 TRAEs were observed in 29.2% and 21.4% of pts in the two cohorts, respectively. Only one pt experienced a grade 4 TRAE in 210 mg dosage of Ph2a. Treatment related SAEs were reported in 10.4% and 8.9% of pts, respectively. No treatment-related deaths were reported.

Conclusions

These findings demonstrate the promising clinical activity and a tolerable toxicity profile of SAF-189s in pts with advanced ROS1+ NSCLC, with or without crizotinib treatment. Clinical trial identification NCT04237805.

Clinical trial identification

NCT04237805.

Editorial acknowledgement

Editorial assistance was provided by Jacqi Pan of Parexel, and funded by Fosun Pharma.

Legal entity responsible for the study

Wanbang Biopharmaceuticals.

Funding

Wanbang Biopharmaceuticals.

Disclosure

Y. Wu: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: BMS, Pfizer. All other authors have declared no conflicts of interest.