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The combination of niraparib and dostarlimab produced a low overall response rate in patients with platinum-resistant ovarian cancer without a known BRCA mutation who had progressed and received prior bevacizumab, one that did not reach the threshold for second-stage accrual to the phase 2 MOONSTONE/GOG-3032 trial.
The combination of niraparib (Zejula) and dostarlimab-gxly (Jemperli) produced a low overall response rate (ORR) in patients with platinum-resistant ovarian cancer without a known BRCA mutation who had progressed and received prior bevacizumab, one that did not reach the threshold for second-stage accrual to the phase 2 MOONSTONE/GOG-3032 trial (NCT03955471).
The doublet elicited an ORR of 7.3% (95% CI, 1.5%-19.9%) in the overall patient population (n = 41). In those with a PD-L1 combined positive score (CPS) of 5% or higher (n = 13), the ORR with the combination regimen was 7.7% (95% CI, 0.2%-36.0%); in those with a PD-L1 CPS of less than 5% (n = 25), the ORR was 8.0% (95% CI, 1.0%-26.0%).
In the overall population, 7.3% of patients achieved a partial response (PR), 22.0% had stable disease, and 58.5% experienced disease progression. Among those in the subset of patients with a CPS of 5% or higher, the PR rate was 7.7%, the stable disease rate was 30.8%, and 53.8% experienced progressive disease. In the group of patients with a CPS of less than 5%, 8.0% experienced a PR, 20.0% had stable disease, and 60.0% experienced disease progression.
The disease control rate (DCR) was 29.3% (95% CI, 16.1%-45.5%) with niraparib plus dostarlimab. In the subsets of patients with a CPS of 5% or higher and less than 5%, the DCRs with the regimen were 38.5% (95% CI, 13.9%-68.4%) and 28.0% (95% CI, 12.1%-49.4%), respectively.
“The ORR observed with niraparib in combination with dostarlimab did not reach the threshold for second-stage accrual, highlighting that platinum-resistant ovarian cancer is difficult to treat and there remains an unmet need for effective treatment for patients with [this disease] and no known BRCA mutations, and prior bevacizumab [Avastin] treatment,” Leslie Randall, MD, MAS, professor in the Department of Obstetrics and Gynecology, of the Division of Gynecologic Oncology at Massey Cancer Center, VCU Health, and colleagues, wrote in a poster on the data.
For the open-label, single-arm, phase 2 trial, investigators sought to examine the safety and efficacy of niraparib plus dostarlimab in patients with advanced, relapsed, high-grade, platinum-resistant ovarian cancer without a known BRCA mutation who had progressed and received prior bevacizumab.
To enroll to the trial, patients were required to be at least 18 years of age and have recurrent high-grade serous, endometrioid, or clear cell ovarian, fallopian tube, or primary peritoneal cancer. They must have previously received 1 to 3 lines of therapy with a platinum, taxane, and bevacizumab.
They must have experienced disease progression less than 6 months from the last administration of platinum-based chemotherapy. They also were required to have measurable disease, an ECOG performance status of 0 or 1, and acceptable organ function.
They could not have previously received treatment with a PARP inhibitor, an anti–PD-1/PD-L1, or anti–PD-L2 agent, nor could they have known deleterious or suspicious deleterious mutations in BRCA1/2. If they experienced progressive disease within 3 months of frontline platinum therapy, they were excluded.
Study participants received intravenous dostarlimab at 500 mg every 3 weeks and oral niraparib at an individualized starting dose of 200 mg once daily.
The primary end point of the trial was ORR per investigator assessment in the overall population and in the subgroup of patients with a PD-L1 CPS of 5% or higher. Key secondary end points included duration of response, disease control rate, progression-free survival, overall survival, and ORR per independent review committee assessment, as well as safety and tolerability.
Exploratory end points comprised efficacy in those with confirmed BRCA wild-type disease, and duration of disease control in those with a best overall response of stable disease, PR, or complete response. Health-related quality of life and disease- and treatment-related biomarkers of response were also evaluated.
At a data cutoff of October 6, 2021, 41 patients were enrolled to the trial. The median age of patients was 65 years (range, 35-77), all were female, 78% were White, 63.4% had an ECOG performance status of 0, and 95.1% had germline BRCA wild-type disease. Regarding PD-L1 status, 31.7% had a CPS of 5% or higher, 61.0% had a CPS of less than 5%, and 7.3% had unknown status.
Moreover, 19.5% of patients previously received 1 line of therapy, 53.7% received 2 prior lines, and 26.8% received 3 prior lines. Most patients become platinum resistant (63.4%), and 36.6% were platinum sensitive to their first line of platinum treatment.
Additional data showed that the median PFS in the overall population was 2.1 months (95% CI, 2.0-2.2). In the subset with a CPS of 5% or higher, the median PFS was 2.2 months (95% CI, 1.6–not evaluable); it was 2.1 months (95% CI, 1.8-2.2) in the subset of patients with a PD-L1 CPS of less than 5%.
PD-L1 status was not found to predict response in this patient population.
Regarding safety, all patents experienced any treatment-emergent adverse effects (TEAEs), and 95.1% had treatment-related toxicities. Moreover, 75.6% of patients experienced any grade 3 or higher TEAEs, and 51.2% had serious TEAEs. Additionally, 70.7% of patients experienced any TEAE that resulted in drug interruption (niraparib, 68.3%; dostarlimab, 0%), reduction (niraparib, 31.7%), or delay (dostarlimab, 34.1%).
The most common AEs associated with either niraparib or dostarlimab included nausea (56.1%), fatigue (34.1%), vomiting (31.7%), anemia (31.7%), platelet count decrease (26.8%), thrombocytopenia (19.5%), constipation (17.1%), diarrhea (14.6%), aspartate aminotransferase increase (14.6%), blood creatinine increase (14.6%), decreased appetite (14.6%), abdominal pain (12.2%), dyspnea (12.2%), hypertension (12.2%), and insomnia (12.2%).
“The safety of the combination was similar to the safety profile of each agent as monotherapy,” the study authors concluded.
Randall LM, O’Malley DM, Monk BJ, et al. MOONSTONE/GOG-3032: interim analysis of a phase 2 study of niraparib + dostarlimab in patients (pts) with platinum-resistant ovarian cancer. J Clin Oncol. 2022;40(suppl 16):5573. doi:10.1200/JCO.2022.40.16_suppl.5573