Surufatinib plus toripalimab combined with pemetrexed (A), and platinum (P) in patients (pts) with advanced non-squamous non-small cell lung cancer (nsq-NSCLC): Updated results of a single-center, phase II trial

BackgroundSurufatinib (S) is a novel, small-molecule inhibitor that simultaneously targets VEGFR1-3, FGFR1 and CSF-1R. Previous reports of NCT05003037 showed promising efficacy of S plus toripalimab (T, an anti-PD-1 antibody) and AP in advanced nsq-NSCLC pts, regardless of driver gene mutations. Here, we present the updated results.MethodsThis single-center, phase Ⅱ study comprises two cohorts. Naive advanced nsq-NSCLC pts without driver gene mutation enrolled in cohort 1 and those with driver gene mutations failing with tyrosine kinase inhibitors (TKIs) assigned to cohort 2. Both cohorts received S (250mg, qd, po) 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.ResultsUp to Apr 15, 2024, 47 pts were recruited in cohort 1 (median age 63 years, male 87.2%, TNM stage IV 100%, brain metastases (BMs) 48.9%). 31 pts were assigned to cohort 2 (median age 58 years, male 48.4%, TNM stage IV 93.6%). The most common mutated genes were EGFR (58.1%), HER2 (12.9%), and MET (6.5%). Most frequently used TKIs included osimertinib (32%) and gefitinib (19%). Among pts with at least one post-baseline tumor assessment (n=43 in cohort 1, 31 in cohort 2), ORRs were 58.1% in each cohort, DCRs were 95.4% and 93.6%. Median PFS was 10.4 months (95%CI 3.5, 17.3) in cohort 1, 10.2 months (95%CI 6.6, 13.7) in cohort 2. Pts without BMs showed longer PFS in both cohorts [cohort 1: 15.4 vs 8.3 months, p=0.095; cohort 2: Not reached (15-month PFS rate 50.84%) vs 8.5m]. Median PFS in 11 microsatellite stable pts of cohort 1 was 15.4 months. The most common grade ≥3 TEAEs in cohort 1 were neutrophil count decreased (17.0%), platelet count decreased (14.9%), and in cohort 2 were platelet count decreased (29.0%), anemia (22.6%).ConclusionsSurufatinib plus toripalimab and AP showed encouraging anti-tumor activity and acceptable safety for the treatment of advanced nsq-NSCLC, especially in patients without brain metastases, regardless of driver gene mutations.Clinical trial identificationNCT05003037.Legal entity responsible for the studySun Yat-sen University Cancer Center.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.