A Phase 1B/2 Multicohort Umbrella Study to Evaluate the Safety and Efficacy of Novel Treatments And/Or Combinations of Treatments in Participants With Ovarian Cancer (OPAL)

Trial ID #	NCT03574779
Phase	II
Drug Class	DNA Damage Repair Pathway Inhibitors: PARP
Drug Name	Niraparib
Alternate Drug Names	MK4827, Zejula
Drugs in Trial	Bevacizumab, Dostarlimab, Niraparib
Eligible Participant	Platinum resistant or refractory ovarian cancer with no prior PARP inhibitor or PD-1/PD-L1 inhibitor
Patients Enrolled	41; median 2 prior therapies; 44% primary platinum resistant; 90% BRCA WT or unknown; 83% w/o HRR gene mutations or unknown
Therapy Setting	Recurrence
Study Design	Open-Label, Non-randomized
Endpoints	ORR, DCR, DoR, PFS, OS, evaluated per RECIST
Biomarkers	Exploratory: prior Bev
Efficacy	ORR: 17.1% (1CR, 6PR) DCR: 73.2% (1CR, 6PR, 23SD) PFS: 7.9 months DoR: 11.8 months OS: 22.1 months Exploratory analysis: prior Bev: w/ prior bev (n=17): ORR: 6% w/o prior bev (n=22): ORR: 27%
Clinically Significant Adverse Events	Serious AE: thrombocytopenia (7.3%), anemia (4.9%), hypertension (4.9%) Grade 3-4 AE: hypertension (26.8%), fatigue (17.1%), anemia (17.1%), 1 grade 4 bowel perforation assessed as related to Bev
Conclusion	Triplet therapy with niraparib, dostarlimab, and bevacizumab is tolerable and demonstrates moderate clinical activity in patients with BRCA WT platinum resistant ovarian cancer
Reference	Liu JF et al. Niraparib, Dostarlimab, and Bevacizumab as Combination Therapy in Pretreated, Advanced Platinum-Resistant Ovarian Cancer: Findings From Cohort A of the OPAL Phase II Trial. JCO Precis Oncol (2024) 8:e2300693 https://pubmed.ncbi.nlm.nih.gov/38754056/