Phase 3 Trial of B7-H4 ADC in Platinum-Resistant Ovarian Cancer: Global 450-Patient Study Begins Enrollment

After platinum-based chemotherapy fails, the drugs available to patients with ovarian cancer often have limited efficacy, and treatment can easily fall into a cycle of brief periods of disease control followed by renewed progression. Now, an antibody-drug conjugate (ADC) targeting the tumor-associated protein B7-H4 has formally entered a global Phase 3 trial to determine whether the tumor shrinkage signals observed in an early-stage study can translate into longer disease control and survival.

The study, named BEHOLD-Ovarian01 and also designated GOG-3132, has enrolled its first participant, with the first enrollment site at the McGill University Health Centre in Canada. The trial is sponsored by GSK and conducted in collaboration with gynecologic oncology research networks including the GOG Foundation, ENGOT, and APGOT. Study registry data indicate that approximately 450 patients with platinum-resistant ovarian cancer are expected to be recruited across multiple countries.

Participants will be randomized to receive mocertatug rezetecan or standard treatment selected by the study physician based on the individual patient’s circumstances. The principal comparator drugs listed in GSK’s study registry include paclitaxel, pegylated liposomal doxorubicin, topotecan, and gemcitabine; ClinicalTrials.gov additionally lists pembrolizumab and bevacizumab as possible combination or treatment options. This design more closely reflects clinical practice in later-line treatment, but because the trial is open-label, imaging assessments will be conducted by independent central review to reduce subjective bias.

The study has two primary endpoints: progression-free survival as assessed by independent central review and overall survival. The former can provide an earlier indication of whether the drug can delay tumor progression, while the latter is the key measure for determining whether a treatment truly extends life. Listing both as primary endpoints also means that tumor shrinkage or short-term disease control alone will not be sufficient to demonstrate that this ADC can change the standard of care.

The rationale for advancing into Phase 3 development comes from the earlier Phase 1 BEHOLD-1 study. External reports indicate that, at the selected dose of 5.8 mg per kilogram, the confirmed objective response rate was 62%. However, Phase 1 trials are typically smaller, lack randomized controls, and may enroll selected patient populations; the response rate can therefore be regarded only as an initial signal of clinical activity and cannot directly predict a survival benefit in the Phase 3 study.

B7-H4 is considered a potential therapeutic target in gynecologic cancers. The ADC strategy uses an antibody to recognize cancer cells bearing this marker and then deliver a cytotoxic drug into the tumor. Its success depends not only on whether the target is present, but is also affected by differences in expression levels, drug release, the bystander effect, and systemic toxicity. BEHOLD-Ovarian01 must therefore also determine which patients are most likely to benefit and whether the efficacy can outweigh the risks of hematologic or other adverse reactions commonly associated with ADCs.

This is the first of five pivotal B7-H4 ADC studies that GSK plans to conduct in ovarian and endometrial cancers. The company’s study registry lists the trial period as June 2026 to December 2029, while ClinicalTrials.gov estimates completion in 2030. The timelines in the two registry entries differ slightly and may still be adjusted depending on the pace of enrollment. For patients and clinicians, the truly decisive data will remain the progression-free survival, overall survival, and complete safety results from the randomized comparison.