Mocertatug Rezetecan Shows High ORR in Ovarian and Endometrial Cancer

Managing platinum-resistant ovarian cancer (PROC) remains a significant hurdle in gynecologic oncology, but interim data from the BEHOLD-1 study (NCT06431594) offers a new reason for optimism. Presented at the 2026 SGO Annual Meeting, the B7-H4–targeted ADC mocertatug rezetecan (GSK5733584) demonstrated encouraging clinical activity and a manageable safety profile in patients with advanced ovarian and endometrial cancers. For oncology nurses, these findings signal a potential new addition to the treatment landscape for high-need populations.

At a median follow-up of 6.1 months (IQR, 4.7-6.6), patients with PROC who received this ADC at the maximum tolerated dose of 5.8 mg/kg every 3 weeks (n = 34) achieved a confirmed overall response rate (ORR) of 62% (95% CI, 44%-78%). The median time to response (TTR) was 1.4 months (IQR, 1.4-1.6). Moreover, patients with endometrial cancer treated at the 4.8 mg/kg dose level (n = 12) experienced a confirmed ORR of 67% (95% CI, 35%-90%).

“B7-H4 is widely expressed in gynecological tumors; in the BEHOLD-1 study, [it was present] in more than 95% of [patients with] PROC and endometrial cancer,” presenting author Ana Oaknin, MD, PhD, the head of the Gynaecologic Cancer Programme at Vall Hebron University Hospital in Barcelona, Spain, said during the presentation. “BEHOLD-1 showed that mocertatug rezetecan delivered rapid and deep responses, with a confirmed ORR of 62% at 5.8 mg/kg in PROC and 67% at 4.8 mg/kg in endometrial cancer.”

What were the key design features of BEHOLD-1?

BEHOLD-1 was a 2-part, open-label, global study that enrolled adult patients with histologically confirmed advanced solid tumors. ^1-3 Patients were also required to have an ECOG performance status of 0 to 2, at least 1 measurable target lesion per RECIST 1.1 criteria, and have received no prior B7-H4–directed therapy. Phase 1b included patients with PROC or endometrial cancer who received 1 to 3 prior lines of therapy; prior treatment with topoisomerase inhibitors was not permitted.

In phase 1B, patients with PROC were randomly assigned 1:1:1 to receive mocertatug rezetecan at 2.8 mg/kg, 4.8 mg/kg, or 5.8 mg/kg every 3 weeks. Those with recurrent/advanced endometrial cancer were randomly assigned 1:1 to receive the agent at 2.8 mg/kg or 4.8 mg/kg every 3 weeks. Study expansion at the recommended dose was informed by the totality of the data.

Baseline patient characteristics were balanced across dose levels. In the PROC cohort (n = 131), the median age was 60 years (range, 38-79). Most patients were White (52%), had an ECOG performance status of 0 (50%), had high-grade serous carcinoma (98%), received prior bevacizumab (Avastin; 79%), and received a prior PARP inhibitor (58%).

In the endometrial cancer cohort (n = 49), the median age was 64 years (range, 31-82). Most patients were White (51%), had an ECOG performance status of 1 (63%), received a prior PD-(L)1 inhibitor (82%), and had B7-H4 tumor membrane positivity (97%).

What were the additional efficacy and safety data?

Additional findings from BEHOLD-1 revealed that patients with PROC who received mocertatug rezetecan at the 2.8 mg/kg (n = 35) and 4.8 mg/kg (n = 34) dose levels achieved confirmed ORRs of 31% (95% CI, 17%-49%) and 53% (95% CI, 35%-70%), respectively. The median TTRs were 2.7 months (IQR, 1.4-2.8) and 2.6 months (IQR, 1.5-2.8), respectively. In the endometrial cancer cohort, the confirmed ORR at the 2.8 mg/kg dose (n = 11) was 9% (95% CI, 0.2%-41%).

In terms of safety, patients with PROC who received mocertatug rezetecan at 5.8 mg/kg (n = 44) experienced any-grade adverse effects (AEs) at a rate of 95%; 66% of these were grade 3 or higher AEs. Treatment-related AEs (TRAEs; 95%), grade 3 or higher TRAEs (64%), as well as TRAEs leading to dose interruption/delay (39%) and reduction (39%) also occurred. Any serious AEs (SAEs; 32%), treatment-related SAEs (18%), and fatal SAEs (2%) were reported in some patients. The most common any-grade AEs included nausea (86%), fatigue (77%), neutropenia (73%), anemia (52%), and alopecia (52%).

In the endometrial cancer cohort, patients treated at the 4.8 mg/kg dose (n = 24) experienced any-grade and grade 3 or higher AEs at respective rates of 100% and 63%. TRAEs, grade 3 or higher TRAEs, TRAEs leading to dose interruption/delay, TRAEs leading to dose reduction, TRAEs leading to treatment discontinuation, any SAEs, treatment-related SAEs, and fatal SAEs were reported at respective rates of 92%, 54%, 21%, 17%, 4%, 25%, 8%, and 4%. The most common any-grade AEs included nausea (79%), neutropenia (58%), and anemia (54%).

“The safety profile was manageable with low discontinuation rates,” Oaknin concluded. “Taken together, these promising results support further investigation [of mocertatug rezetecan] in phase 3 trials at 5.8 mg/kg every 3 weeks.”^2,3

Disclosures: Oaknin holds consulting or advisory roles with Agenus, Amgen, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera, Elsai, EMD Serono, Genmab, GSK, Immunogen, ITeos Therapeutcis, Medison, Merck Sharp & Dohme, Mersana, Novocure, PharmaMar, prIME Oncology, Roche, Shattlucl Labs, Sutro Biopharma, and Tesaro. She received research funding from AbbVie (Inst.), Ability Pharma (Inst.), Advaxis (Inst.), Aeterna Zentaris (Inst.), Agenus, Aprea Therapeutics (Inst.), AstraZeneca (Inst.), BeiGene (Inst.), Belgian Gynaecological Oncology Group (Inst.), Bristol Myers Squibb (Inst.), Clovis Oncology (Inst.), Corcept Therapeutics (Inst.), Elsai Dohme (Inst.), Mundipharma Research (Inst.), Novartis (Inst.), Regeneron (Inst.), Roche (Inst.), Seagen (Inst.), Sutro Biopharma (Inst.), Tesaro (Inst.), and Verastem (Inst.). She also received travel, accommodations, and expenses from AstraZeneca, Clovis Oncology, PharmaMar, and Roche.

References

• Oaknin A, McKean W, van Dongen MG, et al. Mocertatug rezetecan (GSK5733584), a B7-H4-targeted antibody-drug conjugate (ADC), in platinum-resistant ovarian cancer (PROC) and endometrial cancer (EC): first results from the global BEHOLD-1 study. Presented at: 2026 SGO Annual Meeting; April 10-13, 2026; San Juan, Puerto Rico.
• A study to investigate GSK5733584 compared with chemotherapy in participants with platinum-resistant ovarian cancer (BEHOLD-Ovarian01). ClinicalTrials.gov. Updated March 19, 2026. Accessed April 12, 2026. https://clinicaltrials.gov/study/NCT07286266
• A study to investigate gsk5733584 compared with chemotherapy in participants with recurrent endometrial cancer (BEHOLD-Endometrial01). ClinicalTrials.gov. Updated March 11, 2026. Accessed April 12, 2026. https://clinicaltrials.gov/study/NCT07286331