SEP 20, 2021 3:00 AM PDT

An Established Ovarian Cancer Antigen Presents a Promising Therapeutic Target

WRITTEN BY: Katie Kokolus

For the past several decades, cancer antigen 125 (CA 125), a protein located on the surface of ovarian cancer cells, has been used as a diagnostic tool.  Once released from the cell surface, CA 125 can be quantified in the blood and used to screen for ovarian cancer.  Approximately 50% of early-stage and 92% of advanced-stage ovarian cancers exhibit elevated CA 125 levels in the blood. 

OncoQuest Pharmaceuticals has developed a drug called oregovomab, a monoclonal antibody that targets CA 125. 

A recent multicenter phase 2 clinical trial found that oregovomab synergized with standard of care chemotherapy.  Ovarian cancer patients receiving this combination therapy demonstrated significantly improved progression-free and overall survival.   

The promising results of this study were integral in three ongoing clinical trials testing the efficacy of oregovomab in different combination regimens.

Investigators at three sites in Korea are recruiting a cohort of patients with recurrent ovarian cancer. This phase Ib/II trial (NCT04938583) will examine oregovomab combined with chemotherapy and bevacizumab.  

Bevacizumab is a cancer treatment that inhibits a process known as angiogenesis.  During this process, new blood vessels form to deliver oxygen and nutrients to the tumor.  Inhibition of angiogenesis prevents these factors from reaching the tumor, thereby impeding its growth and progression. 

The trial aims to recruit 54 patients and expects to enroll all patients by the end of 2021 and continue collecting data until December 2025.  The researchers will investigate several endpoints, including safety, overall response rate, and survival.

Another phase I/II trial (NCT04620954) combines oregovomab with nivolumab, an anti-PD-1 immune checkpoint inhibitor, and chemotherapy. This study is currently recruiting patients in Singapore.  

Immune checkpoint inhibitors are a class of immunotherapy that prevents binding proteins on T cells to ligands found on tumor cells. Inhibition of this engagement counteracts signals which would restrict the anti-tumor immune response. Thus, the blockade of PD-1 can increase the anti-cancer functions of the immune system.  

This recruitment goal for this study is 31 patients, and the expected completion date is July 2022. The study will evaluate endpoints, including the occurrence of adverse events and progression-free and overall survival.

Finally, a phase III study (NCT04498117) is recruiting patients at 90 centers across the United States. The double-blind, placebo-controlled study will compare the efficacy of oregovomab and chemotherapy to placebo and chemotherapy.

The estimated enrollment of this trial is 602 participants. The research team will evaluate progress-free and overall survival.  The expected completion date of this trial is August of 2027.

If successful, these three trials could demonstrate a highly beneficial effect of a novel drug targeting CA 125.  Moreover, since various cancer types are associated with specific cancer antigens, efficacious targeting of this marker could help direct more opportunities for the treatment of other cancers.   

Sources: CA125, OncoQuest Pharmaceuticals, oregovomab, phase 2, NCT04928583, bevacizumab, NCT04620954, Immune checkpoint inhibitors, PD-1, NCT04498117

About the Author
PhD
PhD in Tumor Immunology. I am interested in developing novel strategies to improve the efficacy of immunotherapies used to extend cancer survivorship.
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