Dr Chase on the Potential Role of B7-H4–Targeted ADCs in Platinum-Resistant Ovarian Cancer

"We have ADCs already available in [platinum-resistant ovarian cancer] but with lower response rates and perhaps worse toxicity. There’s an unmet need to find ADCs with higher response rates and less toxicity."

Dana M. Chase, MD, a professor of clinical obstetrics and gynecology in the Division of Gynecologic Oncology at the David Geffen School of Medicine at UCLA and a member of the UCLA Health Jonsson Comprehensive Cancer Center, discussed updated data from the phase 1 BEHOLD-1 trial (NCT06431594) evaluating the B7-H4–directed antibody-drug conjugate (ADC) mocertatug rezetecan (Mo-Rez) in patients with platinum-resistant ovarian cancer (PROC), and where B7-H4–targeted ADCs may fit in the gynecologic cancer treatment landscape.

In updated BEHOLD-1 findings presented at the 2026 ESMO Congress, at a median follow-up of 13.4 months, Mo-Rez at the 5.8-mg/kg phase 3 dose (n = 45) produced a confirmed objective response rate (ORR) of 62%, with a median duration of response of 12.2 months and a median progression-free survival of 11.1 months. Grade 3 or higher treatment-related adverse effects (TRAEs) occurred in 71% of patients at this dose, although TRAEs led to discontinuation in 2%.

Early-phase response rates are often encouraging, Chase said, but the durability of those responses and data from randomized phase 3 trials in larger populations will be key.

Mo-Rez will likely fit first in pretreated, recurrent PROC, where it is being studied, according to Chase. Available ADCs in this setting offer lower response rates and potentially more toxicity, she noted, and agents that improve on both fronts could make it challenging for approved ADCs to retain a role. Because many ADCs are also moving into frontline trials, the PROC setting could eventually open up, she added.

The role of biomarker testing for newer ADCs remains unclear, Chase said. Higher expression may correlate with greater response, but if most patients express the target—B7-H4 was expressed in more than 95% of evaluable tumors in BEHOLD-1—testing may not be required, she explained. Responses to a folate receptor alpha–targeting ADC presented at the meeting differed by percent positivity, suggesting a differential could emerge, though it may be too early to tell, Chase noted.

Mo-Rez is now being compared with standard of care in PROC in the phase 3 BEHOLD-Ovarian01 trial (NCT07286266), which will help answer those questions, Chase concluded.