496P - Fruquintinib plus sintilimab in patients (pts) with advanced non-small cell lung cancer (NSCLC) with PD-L1-positive expression: A multicenter, single-arm phase II study

Background

Fruquintinib (F, a highly selective VEGFR inhibitor) plus sintilimab (S, an anti-PD-1 monoclonal antibody) showed promising antitumor activity in both pre-clinical and clinical studies. Here, we reported the results of advanced NSCLC cohort with PD-L1-positive expression in an open-label, multi-cohort, single-arm phase 2 study to evaluate the safety and efficacy of F+S.

Methods

Eligible advanced NSCLC pts were those who failed, could not tolerate, were not suitable or unwilling to receive standard treatment; were PD-L1 positive (defined as PD-L1 TPS expression ≥1%); and were without EGFR, ALK or ROS1 genetic alteration if non-sq-NSCLC. Enrolled pts received 21-day cycles of F (5 mg, orally QD, 2 weeks on/1 week off) plus S (200 mg IV, Q3W) until disease progression or intolerable toxicity or the maximum duration of treatment with S (24 mo). The primary endpoint was ORR per RECIST 1.1.

Results

As of May 31, 2023, 13 treatment-naïve pts were enrolled and received treatment of F+S. Median age, 69 yrs (range: 36-75); male, 12 (92.3%) pts; sq-NSCLC, 7 (53.8%) pts; adenocarcinoma, 6 (46.2%) pts. Pts with PD-L1 TPS ≥50% and <50% were 6 (46.2%) and 7 (53.8%), respectively. The median follow-up duration was 17.7 (95%CI: 10.4, 18.4) mo. Among 12 pts with at least one post-baseline tumor assessment, the confirmed ORR was 50.0% (95%CI: 21.1%, 78.9%); DCR was 100% (95%CI: 73.5%, 100%); the median DoR, PFS, and OS were all not reached. 15mo-PFS rate was 55.9% (95%CI: 24.0%, 79.0%), and 18mo-OS rate was 60.6% (95%CI: 29.4%, 81.4%). When stratified by PD-L1 level (TPS ≥50% vs <50%), 15mo-PFS rate were 66.7% (95%CI: 19.5%, 90.4%) vs 42.9% (95%CI: 5.8%, 77.7%), 18mo-OS rate were 66.7% (95%CI: 19.5%, 90.4%) vs 53.6% (95%CI: 13.2%, 82.5%). The median treatment duration of F and S were both 8.3 mo (range 0.7-18.6). All pts experienced TEAEs, and the most common (≥10%) ≥G3 treatment related TEAE was only blood pressure increased (15.4%).

Conclusions

F plus S showed a promising antitumor activity and manageable toxicity for advanced NSCLC with PD-L1-positive status. This study might represent a potential treatment option for these pts, especially for pts who can not tolerate chemotherapy.

Clinical trial identification

NCT03903705.

Editorial acknowledgement

Editorial support is provided by Ye Liu from HUTCHMED Limited.

Legal entity responsible for the study

HUTCHMED Limited.

Funding

HUTCHMED Limited.

Disclosure

All authors have declared no conflicts of interest.