GSK’s Mo-Rez Shows 62% Response Rate in Ovarian Cancer

GSK has reported updated results from the global Phase I BEHOLD-1 trial evaluating mocertatug rezetecan (Mo-Rez), an investigational B7-H4-targeted antibody-drug conjugate (ADC), in patients with platinum-resistant ovarian cancer (PROC). At the selected Phase III dose of 5.8 mg/kg, the Phase Ib analysis showed a confirmed objective response rate (cORR) of 62%, a median duration of response (DoR) of 12.2 months and median progression-free survival (PFS) of 11.1 months.

The findings, based on 45 patients and more than 13 months of follow-up, provide additional evidence of response durability at the selected dose. GSK will present the updated data at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain.

BEHOLD-1 Shows Sustained Antitumour Activity

At 5.8 mg/kg, Mo-Rez produced confirmed responses in 28 of 45 patients (62%; 95% confidence interval [CI], 46.5–76.2%). Median DoR was 12.2 months (95% CI, 7.0–12.7), while median PFS reached 11.1 months (95% CI, 8.3–13.9).

The updated analysis builds on GSK’s earlier report of a 62% response rate in 21 of 34 patients at the same dose. The response rate remains similar in the expanded analysis, while the additional follow-up provides further information on response duration and disease control.

These results are notable in platinum-resistant ovarian cancer, where treatment options remain limited. However, BEHOLD-1 is an early-phase study, and the findings do not establish superiority over existing treatments. Randomised Phase III trials will be needed to determine Mo-Rez’s comparative efficacy and safety.

Safety Profile Requires Continued Assessment

Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 71% of patients (32/45) at the selected dose and were predominantly haematologic. TRAEs led to treatment discontinuation in one patient (2%), while interstitial lung disease (ILD)/pneumonitis was reported in one patient (2%).

Across the broader PROC population treated at the selected dose, TRAEs led to dose interruptions in 51% of patients and dose reductions in 47%. Gastrointestinal and haematological events were among the most common adverse events.

Although treatment discontinuation was uncommon in the 45-patient analysis, the frequency of high-grade toxicity and dose modifications remains clinically relevant. The larger Phase III programme should help establish the safety profile in broader patient populations.

B7-H4 Targeting Supports Further Evaluation

Mo-Rez is an investigational ADC comprising a fully human anti-B7-H4 monoclonal antibody linked to a topoisomerase inhibitor payload, with a drug-to-antibody ratio of six. B7-H4 is an immune checkpoint expressed in several gynaecological cancers and at low levels in normal tissues. The ADC is designed to deliver its cytotoxic payload to target-expressing cancer cells.

Exploratory analyses from BEHOLD-1 identified responses across a range of B7-H4 expression levels. These findings support further investigation of the relationship between target expression and treatment response, but do not establish that B7-H4 expression has no predictive value. GSK will also present exploratory biomarker findings at ESMO 2026.

Five Phase III Trials Underway

GSK is evaluating Mo-Rez across ovarian and endometrial cancers through five pivotal Phase III studies:

• BEHOLD-Ovarian01 (NCT07286266): Platinum-resistant ovarian cancer.
• BEHOLD-Ovarian02 (NCT07684612): Platinum-sensitive ovarian cancer.
• BEHOLD-Ovarian03 (NCT07694427): First-line maintenance treatment for ovarian cancer without homologous recombination deficiency.
• BEHOLD-Endometrial01 (NCT07286331): Second-line advanced or recurrent endometrial cancer.
• BEHOLD-Endometrial02 (NCT07684599): First-line maintenance treatment for mismatch repair-proficient endometrial cancer.

The wider programme includes BEHOLD-1 (NCT06431594), the Phase I monotherapy study, and BEHOLD-2 (NCT06796907), which is evaluating combination treatment.

BEHOLD-1 enrolled 136 patients with PROC overall at the reported data cut-off. The trial is an open-label, two-part Phase I study assessing Mo-Rez’s safety, tolerability and efficacy in PROC and advanced or recurrent endometrial cancer. Its Phase Ib primary endpoint was investigator-assessed cORR under RECIST 1.1. Endometrial cancer patients treated at the selected dose remain under follow-up, with results expected in the future.

Clinical Significance

The updated findings reinforce the evidence of antitumour activity with Mo-Rez at 5.8 mg/kg, with a 62% confirmed response rate and median PFS of 11.1 months. The 12.2-month median DoR adds important information on the durability of responses beyond the earlier analysis.

Nevertheless, the 71% incidence of Grade 3 or higher TRAEs and frequent dose modifications underline the need to assess tolerability alongside efficacy. The ongoing Phase III trials will be critical to establishing whether these early-phase results translate into a clinically meaningful benefit relative to standard treatment.

Reference

GSK presents positive data for Mo-Rez in platinum-resistant ovarian cancer, GSK, 23 October 2026

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of Mocertatug Rezetecan for Injection in Participants with Advanced Solid Tumors (BEHOLD-1), ClinicalTrials.gov ID NCT06431594