Safety/tolerability and preliminary antitumor activity of sitravatinib plus tislelizumab in patients with advanced platinum-resistant ovarian cancer (PROC).

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 FcgammaR 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. Method(s): Anti-PD-(L)1 antibody-naive 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. Result(s): 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 r