Longer Follow-Up of BEHOLD-1 Shows Durable Responses With Mo-Rez in Platinum-Resistant Ovarian Cancer

Mocertatug rezetecan (Mo-Rez) at its recommended dose produced durable responses and the longest progression-free survival (PFS) of the doses tested in patients with platinum-resistant ovarian cancer (PROC), according to updated data with longer follow-up from the phase 1 BEHOLD-1 trial (NCT06431594) presented at the 2026 ESMO Congress.¹

At a median follow-up of 13.4 months (IQR, 10.4-13.9), the confirmed objective response rate (ORR) was 62% (95% CI, 46.5%-76.2%) among patients randomly assigned to Mo-Rez at 5.8 mg/kg every 3 weeks (n = 45), compared with 57% (95% CI, 41.1%-71.1%) at 4.8 mg/kg (n = 46) and 36% (95% CI, 21.9%-51.2%) at 2.8 mg/kg (n = 45). At the 5.8 mg/kg dose, the complete response rate was 11% and the partial response rate was 51%.

The median duration of response (DOR) was 12.2 months (IQR, 7.0-12.7) at 5.8 mg/kg. The median PFS was 11.1 months (IQR, 8.3-13.9) at 5.8 mg/kg vs 8.3 months (IQR, 7.4-10.9) at 4.8 mg/kg and 5.6 months (IQR, 4.0-5.8) at 2.8 mg/kg; the HR for PFS with 5.8 mg/kg vs 4.8 mg/kg was 0.66 (95% CI, 0.4-1.1).

“Mo-Rez administered at a dose of 5.8 mg/kg every three weeks demonstrated durable activity in PROC and is being investigated in five global phase 3 trials spanning ovarian and endometrial cancer,” said Vanda Salutari, MD, of Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome, Italy, who presented the data.

How was the phase 1 BEHOLD-1 trial of Mo-Rez in PROC designed?

Mo-Rez is a B7-H4–directed antibody-drug conjugate with a topoisomerase 1 inhibitor payload. The 2-part, open-label BEHOLD-1 trial included a phase 1a dose-escalation portion in patients with advanced solid tumors and a phase 1b dose-optimization and expansion portion, in which 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. A separate phase 1b cohort enrolled patients with advanced or recurrent endometrial cancer (EC).

Eligible patients had an ECOG performance status of 0 to 2, had at least 1 measurable lesion per RECIST v1.1, and had not received prior B7-H4–directed therapy. Patients in phase 1b had received 1 to 3 prior lines of therapy and no prior topoisomerase 1 inhibitor; a protocol amendment now allows 1 to 4 prior lines. The primary end point was investigator-assessed confirmed ORR per RECIST v1.1; secondary end points included DOR, PFS, and safety.

Among all randomly assigned patients in the PROC cohort (n = 136), the median age was 60.5 years (range, 38-79), 99% had high-grade serous histology, and the median number of prior lines of therapy was 2 (range, 1-5); 36% had received 3 or more prior lines. Prior therapies included bevacizumab (Avastin) in 77% of patients and a PARP inhibitor in 58%. Among patients with evaluable tumor samples (n = 122), 97% had B7-H4 tumor membrane positivity.

What did earlier BEHOLD-1 results show for Mo-Rez in PROC?

First results from BEHOLD-1 were presented at the 2026 Society of Gynecologic Oncology Annual Meeting on Women's Cancer.² Additional data were subsequently presented at the 2026 ESMO Gynaecological Cancers Congress.³ At that analysis, the confirmed ORRs in the PROC cohort were 31% (95% CI, 17%-49%) at 2.8 mg/kg (n = 35), 53% (95% CI, 35%-70%) at 4.8 mg/kg (n = 34), and 62% (95% CI, 44%-78%) at 5.8 mg/kg (n = 34), with a median follow-up of 6.1 months (IQR, 3.7-6.8) in the 5.8 mg/kg group.⁴ Grade 3 or higher treatment-related adverse effects (TRAEs) occurred in 19%, 42%, and 64% of patients at the 3 respective dose levels.

How durable were responses to Mo-Rez in PROC with longer follow-up?

In the updated analysis, responses occurred faster at the highest dose: the median time to response was 42.0 days (IQR, 41.5-50.5) at 5.8 mg/kg vs 80.0 days at both 4.8 mg/kg and 2.8 mg/kg.¹ The median best change in target lesion size was −45.5% (IQR, −78.3% to −27.3%) at 5.8 mg/kg. Two of 4 patients who had received prior mirvetuximab soravtansine-gynx (Elahere) achieved a confirmed response to Mo-Rez across dose levels, and responses at 5.8 mg/kg were seen across B7-H4 expression subgroups.

The 6-month DOR rate was 90% (95% CI, 70%-100%) at 5.8 mg/kg, 70% (95% CI, 50%-90%) at 4.8 mg/kg, and 60% (95% CI, 30%-80%) at 2.8 mg/kg. The median DOR was 6.9 months (IQR, 5.7-9.7) at 4.8 mg/kg and 7.8 months (IQR, 4.4-not estimable) at 2.8 mg/kg. The 6-month PFS rates were 80% (95% CI, 60%-90%), 70% (95% CI, 50%-80%), and 30% (95% CI, 20%-50%) at 5.8 mg/kg, 4.8 mg/kg, and 2.8 mg/kg, respectively.

What was the safety profile of Mo-Rez at each dose in PROC?

In the safety population (n = 45 per dose level), grade 3 or higher TRAEs occurred in 71% of patients at 5.8 mg/kg, 49% at 4.8 mg/kg, and 22% at 2.8 mg/kg. TRAEs led to dose interruption or delay in 51%, 40%, and 9% of patients, respectively, and to dose reduction in 47%, 16%, and 0%; neutropenia was the most common reason for dose reduction at 5.8 mg/kg. TRAEs led to treatment discontinuation in 1 patient (2%) at 5.8 mg/kg, 3 patients (7%) at 4.8 mg/kg, and no patients at 2.8 mg/kg. Treatment-related serious adverse effects occurred in 22%, 13%, and 4% of patients, respectively, and 1 patient at 4.8 mg/kg died of treatment-related pneumonitis.

At 5.8 mg/kg, the most common any-grade TRAEs were nausea (87%), neutropenia (87%), anemia (62%), alopecia (58%), fatigue (53%), and diarrhea (42%). Grade 3 or higher neutropenia, anemia, and thrombocytopenia occurred in 60%, 9%, and 16% of patients at this dose, respectively, and febrile neutropenia occurred in 3 patients (7%), all grade 3. Interstitial lung disease or pneumonitis occurred in 9 patients across the PROC cohort, including 8 at 4.8 mg/kg and 1 at 5.8 mg/kg; 8 of these 9 cases were grade 1 or 2. Primary G-CSF prophylaxis was used in 8% of patients treated at 5.8 mg/kg across the PROC and EC cohorts.

What are the next steps for Mo-Rez in ovarian and endometrial cancers?

The 5.8 mg/kg every-3-weeks dose was selected as the recommended dose for both the PROC and EC cohorts, and an expansion phase at this dose is ongoing. Mo-Rez is being evaluated in 5 global phase 3 trials: vs standard of care in second-line or later PROC (NCT07286266); in combination with bevacizumab vs chemotherapy plus bevacizumab in platinum-sensitive ovarian cancer (NCT07684612); with or without bevacizumab vs active observation with or without bevacizumab as first-line maintenance in non–homologous recombination–deficient ovarian cancer (NCT07694427); vs chemotherapy in second-line or later advanced or recurrent EC (NCT07286331); and in combination with an anti–PD-1 agent vs anti–PD-1 therapy alone as first-line maintenance in mismatch repair–proficient EC (NCT07684599).

Disclosures: Salutari reported contracts with AbbVie, AstraZeneca, Eisai, GSK, Incyte, Menarini Stemline, MSD, and Pharma&.

References

1. Salutari V, Lheureux S, Lim MC, et al. Mocertatug rezetecan (Mo-Rez) in patients with platinum-resistant ovarian cancer (PROC): updated results with longer follow-up from the global BEHOLD-1 study. Presented at: 2026 ESMO Congress; October 23-27, 2026; Madrid, Spain. Abstract LBA41.
2. 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. Gynecol Oncol. 2026;208:S454-S455. doi:10.1016/j.ygyno.2026.02.027
3. 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.
4. Doherty K. Mo-Rez advances into combination studies following robust responses in gynecologic cancers. OncLive. Published August 19, 2026. Accessed November 9, 2026. https://www.onclive.com/view/mo-rez-advances-into-combination-studies-following-robust-responses-in-gynecologic-cancers