Surufatinib (S, a small-molecule inhibitor of VEGFR1-3, FGFR1 and CSF-1R) plus toripalimab (T, an anti-PD-1 antibody) showed encouraging antitumor activity in solid tumors. Here, we report the results of 3 cohorts of advanced G/GEJ adenocarcinoma, ESCC and NEC of an ongoing, multi-cohort, phase 2 study of S + T (NCT04169672).
Patients (pts) with histologically confirmed G/GEJ adenocarcinoma or advanced/metastatic ESCC or advanced NEC who progressed after 1L systemic chemotherapy were enrolled in cohorts A, B, C, respectively. Eligible pts received 21-day cycles of S (250 mg orally QD) plus T (240 mg IV, Q3W). The primary endpoint was objective response rate (ORR) per RECIST 1.1.
Sixty-two pts were enrolled, 21, 20, 21 in cohorts A, B, C, respectively. At data cutoff (Aug 1, 2021), 61 pts (20, 20, 21 in cohorts A, B, C) had at least one post baseline tumor assessment; of them, the confirmed ORR (95%CI) were 30% (11.89-54.28), 30% (11.89-54.28), 23.8% (8.22-47.17) in cohorts A, B, C, respectively, and DCR (95%CI) were 80% (56.34-94.27), 60% (36.05-80.88), 71.4% (47.82-88.72). Median PFS (mPFS) (95%CI): 4.11 mo (2.60-6.90), 2.73 mo (1.25-5.45) and 4.14 mo (1.45-5.45); median OS: not reached (median duration of follow up, 10.09 mo), 9.72 mo (7.79-NR) and 10.87 mo (9.07-NR), respectively. In subgroups of PD-L1 positive pts, in cohort A (defined CPS ≥1), cohorts B and C (CPS ≥5), respectively, the confirmed ORR: 37.5% (15.20-64.57) in 16 pts, 38.5% (13.86-68.42) in 13 pts and 22.2% (2.81-60.01) in 9 pts; mPFS: 4.50 mo (2.60-7.59), 4.27 mo (1.25-5.72) and 5.32 mo (1.18-11.50), respectively. In overall pts (n=62), 27 (43.5%) pts reported G≥3 TRAEs, most commonly (≥3 pts) with neutrophil count decreased, WBC decreased, anemia, hypertension (4 [6.5%], each); and hypertriglyceridemia, hyperglycemia (3 [4.8%], each). Two (3.2%) pts had TRAEs led to treatment discontinuation or death.
S + T exhibited promising efficacy and manageable toxicity in pts with previously treated advanced G/GEJ adenocarcinoma, ESCC and NEC, especially for PD-L1 positive pts.
Clinical trial identification
We thank Xia Yin (medical writer of HUTCHMED) for the abstract editing work.
Legal entity responsible for the study
J. Zhou, H. Shi, P. Tan, S. Fan, W. Su: Financial Interests, Personal, Full or part-time Employment: HUTCHMED. All other authors have declared no conflicts of interest.