Clinical Summary:

• Vanda Salutari, MD, discusses updated results from the phase 1 BEHOLD-1 trial evaluating Mo-Rez, a B7-H4-directed antibody-drug conjugate with a topoisomerase I inhibitor payload, in patients with platinum-resistant ovarian cancer previously treated with chemotherapy.

• Mo-Rez demonstrated a confirmed objective response rate of 62%, a median duration of response of 12.2 months, and a median progression-free survival of 11.1 months at the 5.8 mg/kg dose, although grade ≥3 treatment-related adverse events and dose reductions were frequent.

• These findings support B7-H4 as a promising therapeutic target in platinum-resistant ovarian cancer and warrant further investigation of Mo-Rez, with proactive management of hematologic toxicity remaining important to treatment delivery.

Vanda Salutari, MD, Policlinico Gemelli, Rome, Italy, discusses the rationale for targeting B7-H4 and longer follow-up results from the phase 1 BEHOLD-1 study. At the recommended expansion dose of 5.8 mg/kg every 3 weeks, mocertatug rezetecan demonstrated a confirmed objective response rate of 62%, median duration of response of 12.2 months, and median progression-free survival of 11.1 months. 

The study reported grade ≥3 treatment-related adverse events occurred in 71% of patients at this dose, while treatment discontinuation due to treatment-related adverse events occurred in 2% of patients. Dr Salutari also discusses toxicity management, including neutropenia and the recommendation for prophylactic granulocyte colony-stimulating factor within the BEHOLD program.

Transcript:

Hello, my name is Vanda Salutari. I'm a gynecologic oncologist, and I coordinate an innovative therapy unit in Policlinico Gemelli, Rome. It's my pleasure to present you the updated results of the BEHOLD-1 study.

BEHOLD-1 study is a phase 1 study with a novel B7-H4 ADC called Mo-Rez. B7-H4 is a promising target in gynecological tumors. In fact, it is widely expressed in ovarian cancer and endometrial cancer. On the contrary, it is low expressed in normal tissue. B7-H4 has also another important characteristic that is immunomodulatory and also tumor-promoting.

Mo-Rez is a novel B7-H4 ADC conjugated with a topoisomerase 1 inhibitor. Preliminary results of BEHOLD-1 showed a promising activity and manageable toxicity in platinum-resistant ovarian cancer and recurrent advanced endometrial cancer.

BEHOLD-1 is a phase 1 study characterized by a dose escalation phase 1 followed by a phase 1b dose expansion optimization. In the presentation, we focused on the PROC population in which patients were enrolled in one of the three doses, and at the recommended dose of 5.8 milligrams per kilogram, patients are still followed, and the results are expected for the next year.

The primary end point was objective response rate by investigators following RECIST 1.1. Secondary end points were duration of response, progression-free survival, and safety. In the PROC population, the main eligibility criteria were one to three prior lines of chemotherapy and no prior TOP1 inhibitors.

At the data cutoff in June 2026, 136 patients were enrolled. Looking at baseline characteristics, 36% of patients received more than two prior lines of chemotherapy. Ninety percent expressed B7-H4 positivity in tumors, and most of patients received prior bevacizumab or PARP inhibitors.

About efficacy, Mo-Rez showed, confirmed at the median follow-up of more than 13 months, an objective response rate, very important, 62%, regardless of the levels of B7-H4. At the level of 5.8 milligrams per kilogram, the duration of response was 12.2 months. And considering that the median progression-free survival in platinum-resistant ovarian cancer is four, five months, this duration of response is clinically relevant. Also, progression-free survival increased with the dose level.

At a 5.8-milligram dose level, the median progression-free survival was 11.1 months. Again, in my opinion, clinically relevant.

About safety, grade 3 treatment-related adverse events and more, and dose reduction increased with the dose increasing. And at 5.8 milligrams per kilogram, treatment-related adverse events of grade 3 or more occurred in 71% of patients. And the dose reduction occurred in 47% of patients. The most important adverse event that led to dose reduction was neutropenia. Despite this, the definitive interruption of treatment was very low at 2%.

About toxicity, gastrointestinal toxicity, mostly nausea, and hematological toxicities were the most frequent. Luckily, ILD or pneumonitis occurred in few patients regardless of the dose level. And only one patient in the dose of 5.8 milligrams per kilogram experienced ILD.

About hematological toxicity, neutropenia was the most common grade 3 or higher adverse event, but in the cohort of 5.8 milligrams per kilogram, only 8% of patients received prophylactic G-CSF.

Based on these emerging results, prophylactic use of G-CSF is now recommended in all patients in the BEHOLD program.

In conclusion, B7-H4 is now a promising therapeutic target in the platinum-resistant ovarian cancer population. Mo-Rez confirmed an intriguing and very important clinically meaningful activity at the dosage of 5.8 milligrams per kilogram in the PROC population, with the confirmed objective response rate of 62%, a median duration of response of 12.2 months, and a median progression-free survival of 11.1 months.

Toxicity occurred. It was manageable, and despite dose interruption and reduction, only few patients discontinued permanently the treatment. So, I think that these results in the PROC population, that is [unclear] prognosis population, are significant.

Source:

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 ESMO Congress. October 23-27, 2026; Madrid, Spain. LBA41.