In an early clinical trial, people with certain advanced or treatment-resistant gynecological cancers showed strong responses to the experimental therapy mocertatug rezetecan (Mo-Rez), according to new data announced by its developer, GSK.
Based on these early data, GSK now plans to launch a series of five Phase 3 clinical trials to test Mo-Rez as a potential treatment for gynecologic cancers. Two of the studies have been initiated: BEHOLD-Ovarian01 (NCT07286266), which will test the treatment against standard chemotherapy in people with platinum-resistant ovarian cancer, and BEHOLD-Endometrial01 (NCT07286331), which will compare Mo-Rez against chemotherapy in people with advanced or recurrent endometrial cancer.
Five Phase 3 trials planned across gynecologic cancers
The other planned Phase 3 studies will test the therapy in patients with other subtypes of gynecologic cancer, such as platinum-sensitive ovarian cancer, as well as earlier treatment settings in ovarian and endometrial cancers.
“Treatment of gynecological cancers remains a major challenge, with a pressing need for new therapies that offer improved response rates,” Hesham Abdullah, MD, senior vice president, global head oncology, research and development at GSK, said in a company press release. “With Mo-Rez, we now have compelling evidence of a promising clinical profile, with response rates that support accelerating development into five pivotal global phase III trials later this year across ovarian and endometrial cancers, including earlier-line settings.”
Gynecologic cancers refer to tumors that grow in the female reproductive tract. The most common forms are endometrial cancer — marked by abnormal growth of cells that line the uterus — and ovarian cancer, where tumors form in or around the ovaries. First-line treatments often involve chemotherapy, but tumors can become resistant or come back (recur), which can make treatment more difficult.
Mo-Rez is an antibody-drug conjugate, a type of cancer therapy that combines a tumor-targeting antibody with a cell-killing drug. The antibody is designed to attach to a protein called B7-H4, which is often found on gynecologic cancer cells, helping deliver the drug directly to the tumor.
GSK is sponsoring BEHOLD-1, a Phase 1 study (NCT06431594) testing Mo-Rez in people with various solid tumors, including ovarian and endometrial cancers. The trial is being run at dozens of sites around the world and may still be recruiting.
Early trial shows strong responses in ovarian, endometrial cancers
The company now reports that, among 34 people with platinum-resistant ovarian cancer who received Mo-Rez at a dose of 5.8 mg/kg in the Phase 1 study, 62% responded to the treatment — meaning their tumors shrank. A similar response rate of 67% was seen among 12 patients with recurrent or advanced endometrial cancer who received a dose of 4.8 mg/kg. The upcoming Phase 3 studies will use a dose of 5.8 mg/kg.
The most common side effect in the Phase 1 study was nausea, reported by most participants. Hair loss and fatigue were also commonly reported. Grade 3 or higher treatment-related side effects occurred in more than half of patients and were mainly related to low blood cell counts, which GSK said is expected for this class of therapies. Few patients stopped treatment due to side effects, the company reported.
“In the early [Phase 1] study, we saw meaningful antitumor activity for this patient dataset, with response rates higher than typically seen in [antibody-drug conjugates] in development, and a manageable safety profile. For patients with platinum-resistant ovarian cancer and recurrent endometrial cancer, these findings are particularly encouraging,” said Ana Oaknin, MD, PhD, an investigator for the Phase 1 trial at Hospital Universitario Puerta de Hierro-Majadahonda in Spain.
The BEHOLD-1 study is ongoing and continuing to evaluate Mo-Rez in patients. GSK is also running BEHOLD-2, a separate Phase 1 study (NCT06796907) testing Mo-Rez in combination with other cancer therapies. That study is recruiting participants with various solid tumors at sites worldwide.
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