Background: Combining a PD-1 inhibitor and an agent with immune modulatory and antitumor properties may enhance antitumor activity of either agent. Sitravatinib, a spectrum-selective TKI targeting TAM receptors (Tyro3/Axl/MerTK) and VEGFR2, reduces the number of myeloid-derived suppressor cells and regulatory T cells while increasing the ratio of M1/M2-polarized macrophages, which may overcome an immunosuppressive tumor microenvironment and augment antitumor immune responses. Tislelizumab, an anti-PD-1 antibody engineered to minimize binding to FcγR on macrophages and abrogate antibody-dependent phagocytosis, has shown single-agent clinical activity in patients (pts) with advanced solid tumors. This open-label, multicohort, phase 1b study assessed safety/tolerability and preliminary antitumor activity of sitravatinib + tislelizumab in advanced solid tumors (BGB-900-103; NCT03666143). We report results from the PROC cohort. Methods: Anti-PD-(L)1 antibody-naïve pts with histologically confirmed, advanced PROC (disease progression <6 mo after last platinum treatment) were enrolled. While platinum-resistant pts were included, pts with platinum-refractory disease were excluded. Patients received sitravatinib 120 mg PO QD and tislelizumab 200 mg IV Q3W. Primary endpoint was safety/tolerability of sitravatinib + tislelizumab. Key secondary endpoints were investigator-assessed objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) per RECIST v1.1; overall survival (OS) was also assessed. PD-L1 IHC assay (Ventana SP263) and assessment of plasma VEGF/serum CXCL10 were retrospective. Results: As of Oct 13, 2020, 60 PROC pts were enrolled; 13 (22%) remained on treatment. Median age was 64 yrs (range 26-80); pts received a median of 4 (range 1-11) prior regimens. Median follow-up was 6.0 mo (range 0.2-23.4). Treatment-emergent adverse events (TEAEs) of any grade/grade ≥3 occurred in 97%/68% of pts; TEAEs led to sitravatinib dose reduction in 50% of pts. Nausea (33%), hypertension (18%), and abdominal pain (12%) were the most commonly reported grade ≥3 TEAEs. The 2 fatal AEs (malignant GI obstruction, dyspnea) were deemed unrelated to treatment. Confirmed ORR was 26.4% (95% CI, 15.3-40.3), with 14 pts achieving partial response; DCR was 77.4% (95% CI, 63.8-87.7). Median duration of response was 4.7 mo (95% CI, 2.8-not estimable). There was no clear association between PD-L1 expression and clinical response; plasma VEGF and serum CXCL10 increased after treatment (P<0.0001 for both). Median PFS was 4.1 mo (95% CI, 4.0-5.1); preliminary median OS was 12.9 mo (95% CI, 6.3-17.2). Conclusions: Sitravatinib + tislelizumab was tolerable and showed preliminary antitumor activity in pts with advanced PROC. Further investigation of sitravatinib + tislelizumab in PROC is warranted.

Citation Format: Jeffrey Goh, Jermaine Coward, Bo Gao, Ines P. da Silva, Mark Voskoboynik, Daphne Day, Amy L. Body, Hui K. Gan, Cheng Chen, Xiao Xiang, Cong Fei, Liu Yang, Michael Millward. Safety/tolerability and preliminary antitumor activity of sitravatinib plus tislelizumab in patients with advanced platinum-resistant ovarian cancer (PROC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT013.