Phase 2, single arm clinical trial to evaluate the safety and activity of oregovomab and niraparib as a combinatorial immune priming strategy in subjects with platinum sensitive recurrent ovarian cancer: FLORA-4 study.

Linda R. Duska University of Virginia, Charlottesville, VA info_outline Linda R. Duska, Angeles Alvarez Secord, Debra L. Richardson, Srinivas Rao Jada, Sunil Gupta

Authors Linda R. Duska University of Virginia, Charlottesville, VA info_outline Linda R. Duska, Angeles Alvarez Secord, Debra L. Richardson, Srinivas Rao Jada, Sunil Gupta Organizations University of Virginia, Charlottesville, VA, Division of Gynecologic Oncology, Department of OB/GYN, Duke Cancer Institute of Duke University Health System, Durham, NC, Division of Gynecologic Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, CanariaBio, Inc, Singapore, Singapore, CanariaBio, Inc, Lexington, MA Abstract Disclosures Research Funding CanariaBio, Inc Background: Oregovomab, a murine IgGκ1 MAb, with high affinity binding (1.16 x 10 10 /M −1 ) to the tumor associated antigen CA125 acts as a therapeutic vaccine inducing indirect immunization by cellular and humoral immune responses directed against CA125. We hypothesize that T cells which have been immune sensitized by oregovomab may be further activated in the presence of niraparib mediated induction of STING (STimulator of INterferon Genes). The primary objective was to assess the safety and activity of combination oregovomab and niraparib in platinum sensitive EOC. Methods: An open-label single arm Phase 2 evaluation of the combination of oregovomab and niraparib in subjects previously treated with 1 to 3 lines of platinum-based chemotherapy. All subjects received the niraparib and oregovomab. The daily dose of niraparib was weight based (200-300 mg) taken orally from Day 1 Week 1 to at least the end of Week 12. Oregovomab (2 mg) was administered at Day 1 of Weeks 1, 4, 7, 12, and 20. This study endpoints were disease control rate (DCR) defined as patients that achieved CR, PR and SD; early humoral response; and safety. Results: Between July 2022 and June 2023, 10 eligible patients with a median age was 67.5 years were enrolled, and all patients were included in this analysis. 6 patients had received 2 prior lines and 4 patients had received 1 prior line of chemotherapy. Five patients received prior PARP inhibitors, 1 patient with HRD, and 1 patient with gBRCA mutation. The median number of oregovomab doses administered were 5 (range, 2.0 to 5.0) and median niraparib doses were 118.5 (range, 28.0 to 168.0). Of the 10 patients enrolled, 1 patient (10%) achieved an objective partial response (PR) and 5 patients had disease stabilization (SD), for an overall DCR of 60% at 12 weeks assessment. Of the 5 patients with SD, 2 maintained SD until week 24 assessment while the remaining patients progressed. The duration of response in the 1 patient with objective response was 2.9 months and the median duration of DCR is not evaluable (range 2.9 months - NE). Treatment related all grades adverse events (AEs) to niraparib included anemia (30%), thrombocytopenia (30.0%) and hypertension (30.0%), and oregovomab related all grades AEs included urticaria in 1 patient (10%). Conclusions: Combination oregovomab and niraparib in patients with platinum sensitive EOC was well tolerated with no new safety signals. Translational research is ongoing to assess biomarkers of early humoral response. Clinical trial information: NCT04498117.

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