Pamiparib Plus Tislelizumab Being Studied Further in Ovarian Cancer
Posted: Tuesday, September 17, 2019
Pairing the oral PARP inhibitor pamiparib with the monoclonal antibody tislelizumab produced antitumor responses and was generally well tolerated in 49 patients with advanced solid tumors participating in an open-label phase Ia/b trial. Thirty-four patients had ovarian, fallopian tube, or primary peritoneal cancer. These early results warrant further investigation of the combination, according to Michael Friedlander, MBChB, of Nelune Comprehensive Cancer Centre in Sydney, Australia, and colleagues in The Lancet Oncology.
At a median follow-up of 8.3 months, 10 of the 49 patients (median age, 63 years) had achieved an objective response. Two complete responses were reported in women with BRCA-wildtype ovarian tumors, and seven of eight partial responses were noted in women with ovarian, fallopian tube, or peritoneal cancer (the eighth patient had breast cancer).
The team determined optimal doses for phase II trials: tislelizumab at 200 mg every 3 weeks; pamiparib at 40 mg twice daily. These doses were given in the fourth of the trial’s five different dose-escalation cohorts.
Nausea and fatigue each affected more than half of the study patients. Almost half of these patients (23 of 49) had immune-related adverse events, 9 of which were asymptomatic grade 3 or 4 hepatic immune-related adverse events, reversible with corticosteroids. The most common adverse event of grade 3 or worse severity was anemia, which was reported in six patients.
Together, pamiparib and tislelizumab exploit “the potential accumulation of DNA damage resulting from PARP inhibition, which in turn might increase infiltration of immune cells into the tumor microenvironment, thereby increasing cancer cell killing,” explained Dr. Friedlander and his co-investigators.
Disclosure: The study authors’ disclosure information may be found at thelancet.com.