Safety, tolerability, and preliminary antitumor activity of sitravatinib plus tislelizumab (TIS) in patients (pts) with unresectable locally advanced or metastatic hepatocellular carcinoma (HCC).

• DOI: 10.1200/jco.2022.40.4_suppl.418
• Publication Date: 2022-01-19T20:44:02Z
• Authors: Feng Zhang; Yuxian Bai; Weijia Fang; Zhiqiang Meng; Jianping Xiong; Yabing Guo; Tao Zhang; Jingdong Zhang; Jieer Ying; Zhendong Chen; Zhenggang Ren; Yajin Chen; Chunyi Hao; Liu Yang; Jun Wang; Juan Zhang; Fan Yu; Cong Fei; Xikun Wu; Shukui Qin
• Keywords: Tolerability; Clinical endpoint

418 Background: Sitravatinib is a selective tyrosine kinase inhibitor that reduces the number of myeloid-derived suppressor and regulatory T cells increases ratio M1/M2-polarized macrophages. This may help to overcome an immunosuppressive tumor microenvironment augment antitumor responses. TIS, anti-programmed cell death protein-1 (PD-1) antibody, has shown activity in multiple advanced solid tumors. multicohort, phase 1/2 study assessed safety/tolerability efficacy sitravatinib alone or with TIS (BGB-900-104; NCT03941873). We report results from 2 HCC cohort receiving plus TIS. Methods: Eligible pts were aged ≥ 18 years, had unresectable locally metastatic HCC, received 1 prior lines systemic treatment, ECOG PS 0–1, measurable lesion (per RECIST v1.1), Barcelona Clinic Liver Cancer (BCLC) stage B C disease. Pts anti-PD-1/PD-L1 antibody-naïve must have failed been ineligible for current standard care. 120 mg orally once daily 200 intravenously every three weeks. The primary endpoint was objective response rate (ORR) (RECIST v1.1; by investigator [INV]). Secondary endpoints included duration (DoR), disease control (DCR), progression-free survival (PFS) (all per INV), safety tolerability. Exploratory overall (OS). Results: As July 12, 2021, 43 enrolled (21 antibody naïve 22 refractory/resistant [R/R]) 10 (23.3%) remained on treatment. median age 55 years (range: 29–71), 88.4% male, 74.4% BCLC at entry. With follow-up 8.6 months (mo) 0.7–10.6), confirmed ORR 10.0% (4 pts) (95% CI: 2.8–23.7); all 4 achieved partial Median DoR PFS 5.4 mo 4.1–5.7) 4.8 3.2–6.9), respectively. DCR 85.0% 70.2–94.3). OS not estimable mo–NE); landmark 9 71.4% 47.2–86.0) 52.7% 23.2–75.5) R/R Treatment-emergent adverse events (TEAEs) any grade/grade 3 reported 97.7%/48.8% pts. Serious TEAEs observed 27.9% (n=12). most common grade TEAE palmar-plantar erythrodysesthesia (n=4; 9.3%). experienced led discontinuation both 9.3%) 9.3%), Dose reductions due occurred 15 (34.9%). Conclusions: tolerable showed preliminary pre-treated, HCC. Further investigation this pt population warranted. Clinical trial information: NCT03941873.