Results from a phase Ib study reported at the European Society for Medical Oncology (ESMO) Immuno-Oncology Congress 2019 showed manageable safety and encouraging antitumor activity in patients with advanced ovarian cancer treated with the novel combination of sitravatinib and tislelizumab. These findings were presented by Bo Gao, MD, PhD, of the Blacktown Cancer and Haematology Centre in Blacktown, Australia, and colleagues (Abstract 94O).

Sitravatinib is an investigational orally bioavailable receptor tyrosine kinase inhibitor with immunomodulatory activity as well as potential antitumor activity. Tislelizumab is an investigational humanized IgG4 monoclonal antibody with high affinity and binding specificity for programmed cell death protein 1 (PD-1).

Study Methods

Dr. Gao and colleagues assessed the safety and investigated the antitumor activity of sitravatinib/tislelizumab in an open-label, nonrandomized, multicenter phase Ib study. The trial enrolled patients with solid tumors who were naive to both anti–PD-1 and anti–programmed cell death ligand 1 (PD-L1) therapies; one cohort specifically enrolled patients with recurrent, platinum-resistant, epithelial ovarian cancer.

All patients were treated with 120 mg of sitravatinib once daily in combination with 200 mg of tislelizumab every 3 weeks until disease progression, unacceptable toxicity, death, withdrawal of consent, or study termination. The primary objective was to assess the safety and tolerability of the combination therapy; the secondary endpoints included overall response rate, duration of response, disease control rate, and progression-free survival.

Dr. Gao presented findings from the cohort of patients with ovarian cancer. As of July 2019, 20 women with a median age of 66 years were enrolled in the trial. They had received a median of five prior treatments.

Results

All 20 patients receiving the combination were included in the safety analysis. Grade ≥ 3 treatment-emergent adverse events reported by 10% or more of patients that were determined to be sitravatinib-related by investigators included hypertension in 25% and fatigue in 10%.

Sitravatinib was discontinued by six patients due to a treatment-emergent adverse event. Grade ≥ 3 increased transaminase level was reported in 10% of patients receiving tislelizumab, and three patients discontinued tislelizumab due to treatment-emergent adverse events.

Seventeen patients were evaluable for efficacy; of these, 4 patients achieved confirmed partial response and 11 patients demonstrated stable disease. The median duration of response was not reached (range = 12.29 weeks–not reached).

Only two patients showed progressive disease per Response Evaluation Criteria in Solid Tumors, version 1.1. Median progression-free survival was 18.0 weeks (range = 12.29 weeks–not reached).

The authors concluded, “Combination treatment with sitravatinib and tislelizumab was manageable and showed promising antitumor activity in patients with ovarian cancer.”

Disclosure: The trial was sponsored by BeiGene. For full disclosures of the study authors, visit oncologypro.esmo.org.