Oregovomab Combination to Determine Benefit in Ovarian Cancer

Article

To assess the oregovomab combination, a phase 3 trial has launched for patients with advanced epithelial ovarian cancer.

The phase 3 FLORA-5 (QPT-ORE-005) trial has been launched with used oregovomab (OvaRex) plus paclitaxel and carboplatin to assess survival benefit in patients with advanced epithelial ovarian cancer, according to a presentation from The Society of Gynecologic Oncology 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

Recent Videos
Data from the phase 3 DeLLphi-304 trial at ASCO 2025 revealed a survival advantage with tarlatamab vs chemotherapy in second-line ES-SCLC.
The FDA approval of tarlatamab in SCLC has received much press attention, according to Daniel R. Carrizosa, MD, MS.
The National ICE-T Conference may inspire future collaboration between community and academic oncologists in the management of different cancers.
One of the largest obstacles to tackle in the kidney cancer landscape will be translating the research on rare kidney cancer subtypes into clinical trials.
Long-term toxicities like infections and secondary primary malignancies remain a concern when sequencing novel agents for those with multiple myeloma.
Zanzalitinib exhibited favorable data when evaluated alone or in combination with anti-PD-1 immune checkpoint inhibition in phase 1 RCC trials.
The investigational agent exhibited superior efficacy vs pembrolizumab in patients with lung cancer, suggesting potential efficacy in kidney cancer.
Management of adverse effects and access to cellular therapies among community oncologists represented key points of discussion in multiple myeloma.
“As a community, if we’re looking to help enroll and advocate for patients with rare [kidney cancers], we need to be aware of what is out there,” said A. Ari Hakimi, MD.
Treatment with the dual inhibitor displayed a short half-life and a manageable toxicity profile in patients with clear cell renal cell carcinoma.
Related Content