Phase 3 Trial Seeks to Confirm Oregovomab Benefit in Advanced Ovarian Cancer

Oregovomab (OvaRex), an investigational monoclonal antibody with promising phase 2 data, is being tested in combination with paclitaxel for patients with advanced epithelial ovarian cancer in the phase 3 FLORA-5trial (QPT-ORE-005), which was highlighted during the 2022 SGO Annual Meeting on Women’s Cancer.¹

“Oregovomab is an investigational monoclonal antibody that has been studied in clinical trials for patients with ovarian cancer whose tumor cells express the tumor associated antigen, CA-125 (MUC16),” the investigators noted in a poster presentation during the meeting. “Oregovomab is a novel immunotherapy that enhances the immune response to CA-125.”

The active compound in oregovomab is the murine monoclonal antibody (Mab) B43.12, an IgG1k subclass immunoglobin that functions by binding to CA-125 with high affinity. This compound’s interactions with circulating and tissue-associated CA-125 induces robust immune responses.

The phase 3 double-blind, placebo-controlled, multicenter study has been designed to compare the safety and efficacy of oregovomab plus chemotherapy against placebo plus chemotherapy. Patients will be randomized 1:1 to receive either 2 mg of intravenous oregovomab or placebo, along with 6 standard cycles of paclitaxel/carboplatin.

Additionally, investigators will seek to confirm the clinical benefit observed in a randomized phase 2 study, which demonstrated that adding oregovomab to paclitaxel and carboplatin resulted in clinically significant improvements in PFS and OS.²

At a median follow-up of 42 months, the addition of oregovomab yielded a median PFS of 41.8 months (95% CI, 21.8–not estimable [NE]) compared with 12.2 months (10.4-18.6) with standard chemotherapy (HR, 0.46, 95% CI 0.28-0.70; P = .0027). Regarding OS, the median was not reached with the oregovomab group (45.2-NE), but was 43.2 months (31.8-NE) in the control group (HR, 0.35; 95% CI, 0.16-0.74; P = .043)

Investigators noted that the trial will also seek to evaluate the role of oregovomab as a neoadjuvant chemotherapy (NACT) option.

To be eligible for enrollment, patients must have already received optimal debulking surgery and be either about to begin chemotherapy (cohort 1), or have completed 3 cycles of neoadjuvant therapy and about to resume 3 additional cycles of chemotherapy (cohort 2). Each cohort will be randomized to both treatment regimens.

Key eligibility criteria for enrollment will also include a recent diagnosis of epithelial ovarian , fallopian tube, or peritoneal origin, stage III or IV cancer in accordance to the International Federation of Gynecology and Obstetrics (FIGO), optimal debulking surgery to R1 or R0 stage, an ECOG performance status of 0 or 1, serum CA-125 levels greater or equal to 50 U/mL prior to surgery or chemotherapy, and adequate bone marrow liver, or renal function.

Those who test positive for BRCA1/2 germline gene mutations, has carcinoma, or previously received treatment with other immune-suppressive drugs, are excluded from enrollment. Furthermore, if patients are expected to require additional treatment with PARP inhibitors, bevacizumab (Avastin), or any other investigational agents, or if they harbor active auto-immune diseases, serious illness, clinically significant infections, or a history of more than 1 debulking surgery, they will not be able to enroll on study.

Patients in cohort 1 will receive either oregovomab or placebo on cycles 1, 3, 5, and 5+ of chemotherapy for 12 weeks. Meanwhile, patients in cohort 2 will receive oregovomab or placebo on cycles 4, 6, 6+ for 6 weeks, and 6+ for 18 weeks. Both groups will receive posttreatment follow-up and survival assessment.

The primary objective is progression-free survival (PFS), with secondary objectives including overall survival (OS), safety, and quality of life. Stratification factors include FIGO stage (IIIA/IIIB vs IIIC/IV) and residual disease status after surgical debulking.

References

1. Secord AA, Barroilhet L, Gupta S, et al. FLORA-5/GOG-3035: a phase III double blind placebo controlled multicenter clinical study of front-line chemo-immunotherapy (paclitaxel and carboplatin +/- oregovomab) in patients with advanced epithelial ovarian cancer. Presented at: SGO Annual Meeting on Womens’ Cancer; March 18 -21, 2022; Phoenix, AZ. Abstract 298.
2. Brewer M, Angioli R, Scambia G, et al. Front-line chemo-immunotherapy with carboplatin-paclitaxel using oregovomab indirect immunization in advanced ovarian cancer: A randomized phase II study. Gynecol Oncol. 2020;156(3):523-529. doi:10.1016/j.ygyno.2019.12.024