Mocertatug Rezetecan Drives Rapid, Deep Responses in Platinum-Resistant Ovarian and Recurrent/Advanced Endometrial Cancer

Mocertatug rezetecan (Mo-Rez), a novel B7-H4–directed antibody-drug conjugate, demonstrated rapid and deep responses in patients with platinum-resistant ovarian cancer (PROC) and recurrent or advanced endometrial cancer (EC) across a range of B7-H4 expression levels, according to additional data from an interim analysis of the phase 1 BEHOLD-1 study (NCT06431594). These data were presented at the 2026 European Society for Medical Oncology Gynaecological Cancers Congress.¹

In the PROC cohort, the confirmed objective response rate (cORR) with Mo-Rez 5.8 mg/kg (n = 34) was 62% (95% CI, 44%-78%), and 31 patients achieved stable disease or better. The median time to response (TTR) with Mo-Rez at 5.8 mg/kg was 1.4 months (IQR, 1.4-1.6), and the median follow-up was 6.1 months (IQR, 3.7-6.8). Among patients treated with Mo-Rez 2.8 mg/kg (n = 35) and 4.8 mg/kg (n = 34), respective cORRs were 31% (95% CI, 17%-49%) and 53% (95% CI, 35%-70%). The median TTR in the 2.8 mg/kg group was 2.7 months (IQR, 1.4-2.8), and the median follow-up was 6.1 months (IQR, 5.1-6.5). In the 4.8 mg/kg group, the median TTR was 2.6 months (IQR, 1.5-2.8), and the median follow-up was 6.0 months (IQR, 2.9-7.0).

In the recurrent or advanced EC cohort, the cORR with Mo-Rez 4.8 mg/kg (n = 12) was 67% (95% CI, 35%-90%). The median TTR was 1.5 months (IQR, 1.2-2.7) at 4.8 mg/kg, with a median follow-up of 4.2 months (IQR, 1.7-5.8). At the 2.8-mg/kg dose (n = 11), the cORR was 9% (95% CI, 0.2%-41%). The median TTR in this group was 1.4 months (IQR, 1.4-1.4), with a median follow-up of 4.0 months (IQR, 1.4-5.8).

Based on these results, both the 5.8-mg/kg dose and the 4.8-mg/kg dose have been selected for further evaluation in global phase 3 trials in PROC (BEHOLD-Ovarian01; NCT07286266) and recurrent or advanced EC (BEHOLD-Endometrial01; NCT07286331), respectively.^2,3

"We also saw promising clinical activity in the PROC subgroup after [prior] PARP [inhibition] or bevacizumab [(Avastin) exposure]. And owing to the few number of patients who discontinued treatment due to treatment-related adverse effects [TRAEs], we can confirm the manageable safety profile with few pneumonitis [events].”—Isabelle L. Ray-Coquard, MD, PhD, HDR, presenting author, medical oncologist at the Centre Léon Bérard, and professor of medical oncology at Université Claude Bernard Lyon 1 in Lyon, France.

How was the BEHOLD-1 trial designed?

This 2-part, open-label, phase 1 study enrolled patients aged 18 years or older who had histologically confirmed advanced solid tumors, no prior exposure to B7-H4–directed therapy, an ECOG performance status (PS) of 0 to 2, and at least 1 measurable lesion per RECIST 1.1 criteria.¹ In phase 1b, patients were also required to have received 1 to 3 prior lines of therapy and have no prior exposure to a topoisomerase I inhibitor.

In the phase 1a dose escalation portion (n = 44), patients with advanced solid tumors received Mo-Rez at escalating doses of 2.8 mg/kg, 4.8 mg/kg, 5.8 mg/kg, and 7.2 mg/kg every 3 weeks. The maximum tolerated dose was not reached, and 5.8 mg/kg every 3 weeks was identified as the maximum applicable dose. The data cutoff was July 1, 2025.

In the phase 1b dose optimization/expansion portion, which is the focus of the current analysis, patients with PROC were randomly assigned 1:1:1 to receive Mo-Rez at 2.8 mg/kg, 4.8 mg/kg, or 5.8 mg/kg every 3 weeks. Patients with recurrent or advanced EC were randomly assigned 1:1 to receive Mo-Rez at 2.8 mg/kg or 4.8 mg/kg every 3 weeks. Expansion at the recommended dose was informed by the totality of data.

The primary end point was clinical activity of Mo-Rez assessed by cORR per investigator review using RECIST 1.1 criteria.

What were the baseline characteristics in the phase 1b population?

In the PROC cohort (n = 131), baseline characteristics included the following:

• Median age: 60 years (range, 38-79)
• Race: White, 52%; Asian, 18%; Black or African American, less than 1%; unknown or not reported, 30%
• ECOG PS 0/1: 50%/49%
• Histology: high-grade serous carcinoma/serous adenocarcinoma, 98%/less than 1%; endometrioid adenocarcinoma, less than 1%
• Median prior lines of therapy: 2 (range, 1-5)
• Prior lines of therapy 1/2/3 or more: 20%/43%/37%
• Prior therapies: bevacizumab, 79%; PARP inhibitor, 58%; mirvetuximab soravtansine-gynx (Elahere), 2%; luveltamab tazevibulin, 1%
• B7-H4 tumor membrane positivity: 96% of evaluable samples (n = 111)

In the recurrent or advanced EC cohort (n = 49), baseline characteristics were as follows:

• Median age: 64 years (range, 31-82)
• Race: White, 51%; Asian, 20%; Black or African American, 2%; unknown or not reported, 27%
• ECOG PS 0/1: 38%/63%
• Histology: adenocarcinoma, 6%; endometrioid adenocarcinoma, 39%; serous adenocarcinoma, 24%; mesonephric adenocarcinoma, 6%; carcinosarcoma, 18%; clear cell, 4%; undifferentiated carcinoma, 2%
• Median prior lines of therapy: 2 (range, 1-3)
• Prior lines of therapy 1/2/3: 41%/43%/16%
• Prior therapies: PD-(L)1 inhibitor, 82%; lenvatinib (Lenvima), 27%
• B7-H4 tumor membrane positivity: 97% of evaluable samples (n = 35)

What additional efficacy data were shared from both cohorts?

At the data cutoff, 5% of PROC responders in the 5.8 mg/kg arm experienced disease progression compared with 17% in the 4.8 mg/kg group and 18% in the 2.8 mg/kg group. Among EC responders at the 4.8-mg/kg dose, 12% had progressed at the data cutoff of November 15, 2025; no patients had progressed at this time in the 2.8 mg/kg group.

Among patients with PROC previously treated with a PARP inhibitor in the 2.8 mg/kg (n = 22), 4.8 mg/kg (n = 17), and 5.8 mg/kg (n = 23) groups, cORRs were 18%, 53%, and 65%, respectively. The respective cORRs for patients with prior bevacizumab exposure in the 2.8 mg/kg (n = 29), 4.8 mg/kg (n = 26), and 5.8 mg/kg (n = 27) groups were 24%, 46%, and 59%.

Of note, first results from BEHOLD-1 were also shared during the 2026 Society of Gynecologic Oncology Annual Meeting.⁴

What should be known about the safety profile of Mo-Rez?

The median duration of treatment exposure in the PROC cohort was 4.1 months (range, 0-8) at 2.8 mg/kg, 5.6 months (range, 0-8) at 4.8 mg/kg, and 5.9 months (range, 0-9) at 5.8 mg/kg.¹ The median relative dose intensity (RDI) in these respective groups was 99.2% (range, 88%-102%), 98.8% (range, 63%-101%), and 95.4% (range, 61%-103%). In the EC cohort, the median duration of treatment exposure was 2.4 months (range, 0-7) in the 2.8 mg/kg group and 4.0 months (range, 0-6) in the 4.8 mg/kg group. Respective median RDIs were 99.6% (range, 85%-207%) and 98.8% (range, 43%-102%).

The incidence of TRAEs leading to treatment discontinuation remained low across all dose levels. In the PROC cohort, any-grade TRAEs were reported in 93% of patients at 2.8 mg/kg, 86% at 4.8 mg/kg, and 95% at 5.8 mg/kg. Grade 3 or higher TRAEs occurred in 19%, 42%, and 64% at these 3 respective doses. TRAEs leading to dose interruption/delay were reported in 5%, 28%, and 39% of patients, and TRAEs leading to dose reduction occurred in 0%, 14%, and 39%, respectively. TRAEs leading to treatment discontinuation were reported in 0%, 5%, and 0% of patients at these respective dose levels. Treatment-related serious AEs (SAEs) occurred in 5%, 12%, and 18% of patients. One treatment-related fatal SAE was reported at 5.8 mg/kg.

In the recurrent or advanced EC cohort, any-grade TRAEs were reported in 92% of patients at both the 2.8-mg/kg and 4.8-mg/kg dose levels. Grade 3 or higher TRAEs occurred in 17% of patients at 2.8 mg/kg and 54% at 4.8 mg/kg. TRAEs leading to dose interruption/delay were reported in 13% and 21% of patients, respectively; TRAEs leading to dose reduction occurred in 0% and 17% of patients. TRAEs leading to treatment discontinuation were reported in 4% of patients at both dose levels. Treatment-related SAEs occurred in 0% and 8%, and 1 fatal SAE was reported in the 4.8 mg/kg EC cohort, though it was not considered treatment-related.

Interstitial lung disease (ILD)/pneumonitis was reported in 3% of the phase 1b safety population (n = 178), comprising 3 grade 1 and 2 grade 2 events. No ILD/pneumonitis events of grade 3 or higher were reported at the 5.8-mg/kg every-3-weeks dose level.

Disclosures: Ray-Coquard disclosed contracts with AbbVie, Agenus, AstraZeneca, BeiGene, Bristol Myers Squibb, Corcept Therapeutics, Daiichi Sankyo, Deciphera, Eisai, Genmab, Gilead Sciences, GSK, Incyte, MSD, Novartis, Pharma&, Regeneron Pharmaceuticals, Roche, Scorpion Therapeutics, Sutro Biopharma, TORL BioTherapeutics, Tubulis, and Zentalis Pharmaceuticals.

References

1. Ray-Coquard I, McKean W, van Dongen MG, et al. Mocertatug rezetecan (Mo-Rez), a B7-H4 targeted antibody-drug conjugate, in platinum-resistant ovarian cancer and endometrial cancer: additional data from BEHOLD-1 study. Presented at: 2026 ESMO Gynaecological Cancers Congress; June 17-19, 2026; Copenhagen, Denmark. Abstract 110RO.
2. A study to investigate mocertatug rezetecan compared with standard of care in participants with platinum-resistant ovarian cancer (BEHOLD-Ovarian01). ClinicalTrials.gov. Updated May 27, 2026. Accessed June 17, 2026. https://clinicaltrials.gov/study/NCT07286266
3. A study to investigate mocertatug rezetecan compared with chemotherapy in participants with endometrial cancer after platinum-based chemotherapy and immunotherapy (BEHOLD-Endometrial01). ClinicalTrials.gov. Updated May 27, 2026. Accessed June 17, 2026. https://clinicaltrials.gov/study/NCT07286331
4. 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 Society of Gynecologic Oncology Annual Meeting; April 10-13, 2026; San Juan, Puerto Rico.