First Patients Dosed in New CA125 Antagonist Study in Ovarian Cancer

Two international studies of oregovomab in combination with other anticancer therapies for the treatment of previously treated, recurrent ovarian cancer have dose its first patients, and patients are being recruited to receive the drug in a phase 3 study conducted in the United States, according to a press release by Quest PharmaTech Inc.¹

Oregovomab is a murine IgC that acts against CA 125. Previous studies have found that adding the agent to standard of care chemotherapy helps to extended progression-free survival (PFS) and overall survival (OS). Additionally, oregovomab was found to reduce the risk of death by more than 50% compared to a placebo and did not add to regimen toxicity. 

"We are committed to continue to work with investigators to explore the potential of oregovomab in combination therapies for treating ovarian cancer in both front line and recurrent settings,” said Ragupathy Madiyalakan, PhD, chairman of OncoQuest, in a press release. "These additional clinical studies will guide us to select the optimal combinations for treatment throughout the course of this difficult disease.”

The first phase 1/2 study (NCT04938583) is evaluating the agent in combination with bevacizumab (Avastin) plus chemotherapy in BRCA wild type platinum-sensitive recurrent ovarian cancer. The trial has an estimated enrollment of 54 participants and an estimated completion date of December 2025. Primary end points include safety and tolerability, and overall response rate. Secondary end points include progession-free survival (PFS) and overall survival (OS).²

During the single-arm study, all patients will receive the combination of oregovomab, bevacizumab, paclitaxel, and carboplatin. It will follow a 3 + 3 dose design with a starting dose of 2mg of oregovomab.

In order to participate, patients must be female and 19 years old or older with CA125-associated recurrent epithelial adenocarcinoma of ovarian, fallopian tube, or peritoneal origin, have a complete or partial response to front-line platinum-based therapy, an ECOG performance status of 0, 1, or 2, and adequate organ function. Patients who have received more than one line of chemotherapy, an active autoimmune disease, the use of immunosuppressants within 28 days of first dose, previous solid organ transplantation, or have previously received oregovomab or bevacizumab.

The study is currently recruiting in 3 hospitals across Korea.

The second phase 1/2 study (NCT04620954)³ is looking at the combination of oregovomab, nivolumab (Opdivo), and chemotherapy in patients with epithelial cancer of ovarian, tubal, or peritoneal origin. It has an estimated enrollment of 31 participants and an estimated study completion date of July 2022. Primary end points include the number of incidences of adverse events and best overall response. Secondary end points include stable disease, PFS, and OS.

During the study, all patients received the triplet combination. 

In order to participate, patients must be 21 years of age or older, have measurable disease, have progressive disease, an estimated life expectancy of more than 3 months, an ECOG status of 0 or 1, and adequate organ function. Patients with non-epithelial ovarian cancer, active central nervous system metastases, spinal cord compression, or leptomeningeal carcinomatosis are not eligible to participate.

The study is currently recruiting in Singapore.

These 2 studies are in addition to an ongoing United States study that is evaluating oregovomab plus chemotherapy in patients with newly diagnosed epithelial ovarian cancer following optimal debulking surgery. The phase 3 study (NCT04498117) has an estimated enrollment of 602 participants. The primary end point is PFS. The secondary end point is OS.⁴

That study is currently recruiting in 90 locations across Arizona, California, Colorado, Connecticut, Florida, Georgia, Indiana, Louisiana, Massachusetts, Michigan, Minnesota, New Jersey, North Carolina, Ohio, Oklahoma, Pennsylvania, Rhode Island, South Dakota, Tennessee, Texas, Virginia, Washington, and Wisconsin.

_REFERENCES: 

_{1.OncoQuest Pharmaceuticals Inc. announces first patient enrolled in each of two investigator initiated clinical trials of oregovomab in combination therapy for the treatment of recurrent ovarian cancer. News release. Oncoquest. September 1, 2021. Accessed September 2, 2021. https://prn.to/2YlL7A1} 

_{2.Oregovomab in combination with bevacizumab plus chemo in BRCA wild type platinum sensitive recurrent ovarian cancer. ClinicalTrials.Gov. Accessed September 2, 2021. https://bit.ly/3gRE2xx.}

_{3.Clinical trial of chemotherapy, oregovomab and nivolumab in patients with epithelial cancer of ovarian, tubal or peritoneal Origin (ORION-02). ClincialTrials.gov. Accessed September 2, 2021. https://bit.ly/3gSAwTl.}

_{4.Oregovomab plus chemo in newly diagnosed patients with advanced epithelial ovarian cancer following optimal debulking surgery (FLORA-5). ClinicalTrials.gov. Accessed September 2, 2021. https://bit.ly/3BB8QKW.}