124P - Surufatinib plus toripalimab combined with etoposide (E) and cisplatin (P) in patients (pts) with advanced naive small cell lung cancer (SCLC) -Updated results of a phase ?b/? trial

Background

Surufatinib (S) is a novel, small-molecule inhibitor that simultaneously targets VEGFR1-3, FGFR1 and CSF-1R. In a phase 2 study, S plus toripalimab (T, an anti-PD-1 antibody) showed promising efficacy in advanced SCLC pts failing with first-line(1L) chemotherapy. We previously reported preliminary results of NCT04996771, which demonstrated that S plus T and EP had encouraging efficacy as 1L regimen for SCLC. Here, we present an updated results.

Methods

This single-arm, open-label study consists of 3+3 dose-escalation (phase Ⅰb) and dose expansion (phase II). Eligible pts were≥18 years old with histologically confirmed advanced SCLC, ECOG PS 0-1, with at least one measurable lesion. Pts with treated, stable, and asymptomatic brain metastases are allowed. In phase Ib, S was dosed at 150mg - 250mg qd, po, Q3W, in combination with a fixed dose of T (200mg, iv, d1, Q3W) and EP (Q3W). After 4 cycles followed by maintenance therapy with S plus T, Q3W. The primary endpoints are RP2D of S and PFS. The secondary endpoints include ORR, DCR, OS, and safety.

Results

At cutoff date (Aug 31, 2023), 39 pts were enrolled. The median age was 64 years with male 82.1%, ECOG PS 1 59.0%, TNM stage IV 89.7%. Pts with liver, bone, and brain metastases were 33.3%, 30.8%, and 12.8%, respectively. The RP2D of S was identified as 200mg, po, qd, Q3W. Among pts with at least one post-baseline tumor assessment (n=35), median PFS was 6.0 months (95%CI 4.7, 7.3). Compared with pts with liver metastases, pts without metastases showed significantly longer PFS (5.7m vs 8.4m, p=0.0169). So as pts with or without bone metastases (5.7m vs 8.4m, p=0.0198). The ORR was 97.1% and DCR was 100%. The most common (≥10%) grade ≥3 treatment-emergent adverse events (TEAEs) were neutrophil count decreased (31.6%), white blood cell count decreased (23.7%), and platelet count decreased (10.5%).

Conclusions

Surufatinib plus toripalimab combined with etoposide and cisplatin showed encouraging anti-tumor activity and acceptable toxicity for the 1L treatment of advanced SCLC, especially in patients without liver metastases or bone metastases. The combination of the 4 agents might be a novel first-line therapeutic option for SCLC.

Clinical trial identification

NCT04996771; Release date: November 9, 2021.

Legal entity responsible for the study

Sun Yat-sen University Cancer Center.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.