74P - A single-center, Phase II study of surufatinib combined with toripalimab, pemetrexed(A), and platinum (P) in patients with advanced non-squamous non-small cell lung cancer (nsq-NSCLC)

Background

Surufatinib (S, a small-molecule inhibitor of VEGFR1-3, FGFR1 and CSF-1R) has exhibited encouraging efficacy in NSCLC patients (pts) as 3^rd line or futher therapy in a phase II trial (NCT04922658). The purpose of this study is to evaluate the efficacy and safety of S + Toripalimab (T, an anti-PD-1 antibody) + chemotherapy (AP) in nsq-NSCLC pts. Here, we report the preliminary results.

Methods

This single-arm, phase Ⅱ study (NCT05003037) has two cohorts. Naive advanced nsq-NSCLC pts without driver gene mutation were enrolled in cohort 1and pts with mutated driver genes failing with tyrosine kinase inhibitors (TKIs) entered cohort 2. Both cohorts received S (250mg, qd, po, adjusted by DLTs in 1^st cycle) plus T (240mg, iv, d1, q3w, fixed dose) and AP (q3w). After 4 cycles followed by maintenance therapy with S plus T and A, q3w. Primary endpoint is PFS. Secondary endpoints include ORR, DCR, OS, and safety.

Results

Until Sep 5, 2023, 40 pts were enrolled in cohort 1 (median age 60 years, male 89.7%, TNM stage IV 100%, brain metastases (BMs) 48.7%). 25 pts were assigned to cohort 2 (median age 58 years, male 48%, TNM stage IV 96%). The most common mutated genes were EGFR (64%), HER2 (16%), and MET (8%). Most commonly used TKIs included osimertinib (36%), gefitinib (24%), and almonertinib (24%). RP2D of S was 250mg, po, qd, q3w in both cohorts (1/0 DLT occurred in 6 pts in cohort 1/2). Among pts with at least one post-baseline tumor assessment (n=38 in cohort 1, 24 in cohort 2), ORRs were 57.9% and 54.2%, DCRs were 94.7% and 95.8%. Median PFS was 10.2 months (95%CI 6.8, 13.4; BMs: 7.2m; non-BMs: not reached) in cohort 1, was not reached in cohort 2. The most common treatment-emergent adverse events (Total; Grade ≥3) in cohort 1 were diarrhea (67.5%; 2.5%), proteinuria (57.5%; 5.0%), and anemia (50.0%; 2.5%); in cohort 2 were decreased platelet count (56.0%; 32.0%), fatigue (48.0%; 0) and diarrhea (40.0%; 0).

Conclusions

Surufatinib plus toripalimab and AP showed promising anti-tumor activity and acceptable toxicity for the treatment of advanced nsq-NSCLC, whether the driver gene is mutated or not. The combination of the 4 agents might be a novel therapeutic option for advanced nsq-NSCLC.

Clinical trial identification

NCT05003037; Release date: December 8, 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.