In an Australian phase Ia/b trial reported in The Lancet Oncology, Friedlander et al found evidence of activity of the combination of the poly (ADP-ribose) polymerase inhibitor pamiparib and the programmed cell death protein 1 inhibitor tislelizumab in patients with previously treated advanced solid tumors.
In the dose-escalation phase of the multicenter study, 49 patients who had received one or more previous line[s] of therapy were treated between January 2016 and May 2017. Patients were enrolled into one of five cohorts and treated with either tislelizumab at 2 mg/kg every 3 weeks plus pamiparib at 20, 40, or 60 mg twice daily (cohorts 1, 2, and 3) or tislelizumab at 200 mg every 3 weeks plus pamiparib at 40 or 60 mg twice daily (cohorts 4 and 5). The most common primary tumor sites was the ovary, fallopian tube, or peritoneum (n = 34).
Responses
Objective response was observed in 10 (20%) of all 49 patients who received at least one dose of study treatment, including a complete response in 2 patients. An additional 16 patients (32%) had stable disease. Response was observed in 9 (27%) of 34 patients with ovarian disease, including a complete response in 1 patient; an additional 7 patients (21%) had stable disease. Responses were observed in patients with both wild-type and germline BRCA-mutant status.
KEY POINTS
- The recommended phase II dose was tislelizumab at 200 mg every 3 weeks plus pamiparib at 40 mg twice daily.
- Objective response was observed in 10 (20%) of 49 patients, with stable disease in 16 (32%).
Toxicity
Dose-limiting toxicities occurred in four patients, consisting of intractable grade 2 nausea, grade 3 rash, grade 2 nausea and vomiting, and grade 4 immune-mediated hepatitis. Immune-related adverse events occurred in 23 patients (47%), with 9 of these patients (39%) having asymptomatic grade 3 or 4 hepatic events. The most common adverse event of grade ≥ 3 was anemia (12%). The recommended phase II dose was tislelizumab at 200 mg every 3 weeks plus pamiparib at 40 mg twice daily.
The investigators concluded, “Pamiparib with tislelizumab was generally well tolerated and associated with antitumour responses and clinical benefit in patients with advanced solid tumors, supporting further investigation of the combination of pamiparib with tislelizumab.”
Michael Friedlander, MBChB, of Nelune Comprehensive Cancer Centre, University of New South Wales Clinical School, Sydney, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by BeiGene. For full disclosures of the study authors, visit thelancet.com.
