Results of a phase Ib study reported at the ESMO Immuno-Oncology Congress 2019 in Geneva, Switzerland (11-14 December) show manageable safety and encouraging anti-tumour activity in patients with advanced ovarian cancer treated with the novel combination of sitravatinib and tislelizumab.
Bo Gao, of the Oncology department of the Blacktown Cancer and Haematology Centre in Blacktown, Australia, explained that sitravatinib is an investigational, orally bio-available, receptor tyrosine-kinase inhibitor with immune modulatory activity as well as potential anti-tumour activity, while tislelizumab is an investigational, humanised IgG4 monoclonal antibody with high affinity that specifically binds PD-1.
Dr. Gao and colleagues assessed the safety and investigated the anti-tumour activity of sitravatinib plus tislelizumab in an open-label, non-randomised, multicentre, phase Ib study (NCT03666143). The trial enrolled patients with diverse solid tumours who were naive to both anti-PD-1 and anti-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 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 and the secondary endpoints included overall response rate, duration of response (DoR), disease control rate, and progression-free survival (PFS).
Dr. Gao presented findings from the cohort of patients with ovarian cancer. As of 17 July 2019, 20 women with a median age of 66.0 years were enrolled. They had received a median of 5 prior treatments (range, 2 to 12).
Nearly half of the patients discontinued treatment due to treatment-emergent adverse events
All 20 patients receiving the study drugs were included in the safety analysis. Grade ≥3 treatment-emergent adverse events (TEAEs) reported by 10% or more of patients that were determined to be sitravatinib-related by investigators included hypertension in 25% and fatigue in 10% of patients. Sitravatinib was discontinued by 6 patients due to a TEAE. Grade ≥3 increased transaminases that was related to tislelizumab was reported in 10% of patients and 3 patients discontinued tislelizumab due to a TEAE.
Partial responses and disease control in heavily pre-treated patients
Seventeen patients were evaluable for efficacy; of these 4 patients achieved confirmed partial response, and 11 patients demonstrated stable disease. The median DoR was not reached (NR; range, 12.29 weeks to NR).
Only 2 patients showed progressive disease per RECIST version 1.1.
Median PFS was 18.0 weeks (range, 12.29 weeks to NR).
Based on these findings the authors concluded that combination treatment with sitravatinib and tislelizumab showed manageable safety and promising anti-tumour activity in patients with advanced ovarian cancer.
This trial was sponsored by BeiGene.
94O – Gao B, Goh J, Markman B, et al. Safety and antitumor activity of sitravatinib in combination with tislelizumab in patients with advanced solid tumors: Ovarian cancer cohort data.