Surufatinib/Toripalimab Shows Encouraging Activity in NSCLC and SCLC

Surufatinib/toripalimab elicited a median PFS of 9.6 months in patients with treatment-naïve NSCLC and 3.0 months in patients with pretreated SCLC in a phase 2 trial.

Surufatinib (Sulanda) in combination with toripalimab-tpzi (Loqtorzi) demonstrated positive antitumor activity as well as an acceptable safety profile in the treatment of patients with advanced or metastatic PD-L1–positive non–small cell lung cancer (NSCLC) that was treatment-naïve and small cell lung cancer (SCLC) that was previously treated, according to results from a phase 2 study (NCT04169672) published in Springer Nature.

At the data cutoff of February 28, 2023, the overall response rate (ORR) in the NSCLC cohort was 57.1% (95% CI, 34.0%-78.2%) with a disease control rate (DCR) of 100% (95% CI, 83.9%-100.0%); partial responses (PRs) were achieved by 57.1% of patients, and 42.9% had stable disease. In the SCLC cohort, the ORR was 15.8% (95% CI, 3.4%-39.6%) with a DCR of 94.7% (95% CI, 74.0%-99.9%); PRs were achieved by 15.8% of patients, 78.9% had stable disease, and 5.3% had disease progression.

The median progression-free survival (PFS) in the NSCLC cohort was 9.6 months (95% CI, 5.5-not applicable [NA]); the 3-month PFS rate was 82.2% (95% CI, 59.2%-92.9%), the 6-month PFS rate was 59.3% (95% CI, 36.4%-76.4%), and the 9-month PFS rate was 54.4% (95% CI. 31.8%-72.4%). In the SCLC cohort, the median PFS was 3.0 months (95% CI, 2.8-4.1); the 3-month PFS rate was 47.4% (95% CI, 24.4%-67.3%), the 6-month PFS rate was 15.8% (95% CI, 3.9%-34.9%), and the 9-month PFS rate was 15.8% (95% CI, 3.9%-34.9%).

The median overall survival (OS) in the NSCLC cohort was 24.3 months (95% CI, 10.8-NA); the 6-month OS rate was 73.9% (95% CI, 50.9%-87.3%), the 9-month OS rate was 73.9% (95% CI, 50.9%-87.3%), and the 12-month OS rate was 65.2% (95% CI, 42.4%-80.8%). In the SCLC cohort, the median OS was 11.0 months (95% CI, 5.0-15.7); the 6-month OS rate was 75.0% (95% CI, 50.0%-88.8%), the 9-month OS rate was 60.0% (95% CI, 35.7%-77.6%), and the 12-month OS rate was 45.0% (95% CI, 23.1%-64.7%).

“This combination regimen with surufatinib plus toripalimab showed preliminary antitumor activity in patients with treatment-naive advanced or metastatic PD-L1–positive NSCLC or previously treated SCLC, with a manageable safety profile,” lead study author Ying Cheng, from the Department of Oncology at Jilin Cancer Hospital, and fellow authors, wrote in the paper. “Particularly, if further validated in a larger population, this combination treatment may offer a potential chemotherapy-free option for these patients.”

The trial enrolled a total of 43 patients; 23 of whom were in the NSCLC cohort and 20 in the SCLC cohort. Eligible patients were aged 18 to 75 years with histologically or cytologically confirmed treatment-naïve unresectable or metastatic advanced NSCLC or SCLC that was previously treated at least 6 months before enrollment without relapse or metastasis or that progressed after first-line systemic chemotherapy. Additional enrollment criteria were a PD-L1 tumor proportion score of at least 1%, an ECOG performance status of 0 or 1, at least 1 measurable lesion, and adequate organ function.

Patients with prior treatment with immune checkpoint inhibitors or anti–VEGF/VEGFR-targeted therapies or radical radiotherapy who had uncontrolled brain metastases were among those excluded from participation.

In the NSCLC and SCLC cohorts, the median age of patients was 66 and 58 years, respectively. All patients in both cohorts were Asian, 95.7% and 85.0% had an ECOG performance status of 1, 95.7% and 100.0% did not have brain metastases, and 60.9% and 50.0% had at least 3 organs involved.

Patients received 250 mg of oral surufatinib once daily with 240 mg of intravenous toripalimab once every 3 weeks for a maximum duration of 24 months with toripalimab treatment.

The primary end point was ORR per RECIST v1.1 criteria. Secondary end points included duration of response, PFS, DCR, OS, and safety.

Overall, 95.3% of patients experienced at least 1 treatment-related adverse event (TRAE); of grade 3 or higher events, TRAEs were experienced by 60.9% of the NSCLC cohort and 50.0% of the SCLC cohort. Surufatinib-related AEs were observed in 95.7% and 95.0%, respectively, with 56.5% and 50.0% leading to surufatinib dose interruption or dose reduction. Toripalimab-related AEs occurred in 95.7% and 85.0% of patients, with 26.1% and 35.0% leading to toripalimab interruption. Treatment-related serious AEs occurred in 30.4% and 30.0% of patients, and TRAEs leading to death occurred in 8.7% of patients in the NSCLC cohort and 0% in the SCLC cohort.

Reference

Cheng Y, Zhang P, Lu M, et al. Efficacy and safety of surufatinib plus toripalimab in treatment-naive, PD-L1-positive, advanced or metastatic non-small-cell lung cancer and previously treated small-cell lung cancer: an open-label, single-arm, multicenter, multi-cohort phase II trial. Cancer Immunol Immunother. 2025;74(3):83. Published 2025 Feb 1. doi:10.1007/s00262-024-03932-x