Dr Backes on BEHOLD-1 Data With Mocertatug Rezetecan in Platinum-Resistant Ovarian Cancer

"Sometimes these high objective response rate[s] don't always translate [into] a recurrence-free survival, progression-free survival benefit. But for these ADCs and especially these [B7-H4–directed agents], already in their early phase studies we see long progression-free survival times."

Floor Backes, MD, director of the Division of Gynecologic Oncology, a board-certified gynecologic oncologist, and a tenured professor at The Ohio State University Wexner Medical Center and the Ohio State University Comprehensive Cancer Center–James, discussed updated findings 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), as well as where ADCs may fit in ovarian cancer care and the practical challenges of using them.

At the 2026 ESMO Congress, updated data from the PROC cohort of BEHOLD-1 (n = 136; median follow-up, 13.4 months) showed a confirmed objective response rate (ORR) of 62% (95% CI, 46.5%-76.2%) with Mo-Rez at 5.8 mg/kg every 3 weeks (n = 45) vs 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). The median progression-free survival (PFS) was 11.1 months (IQR, 8.3-13.9), 8.3 months (IQR, 7.4-10.9), and 5.6 months (IQR, 4.0-5.8), respectively, and the median duration of response at 5.8 mg/kg was 12.2 months (IQR, 7.0-12.7).

High ORRs do not always translate into a PFS benefit, Backes noted, but B7-H4–directed ADCs are already showing long PFS in early-phase studies. Because the cohorts remain small and follow-up is limited, confirmation in phase 3 trials is needed. The phase 3 BEHOLD-Ovarian01 trial (NCT07286266), for which Backes is principal investigator, is comparing Mo-Rez with standard of care in PROC.

Many ADCs presented at the meeting produced high confirmed ORRs and encouraging PFS, Backes said. Mirvetuximab soravtansine-gynx (Elahere) offers greater benefit in tumors with high folate receptor α (FRα) expression, whereas many newer ADCs appear active regardless of target expression, which she called both exciting and confusing when choosing among agents. In BEHOLD-1, 97% of evaluable tumors were B7-H4 positive, and responses occurred across expression levels. Additional data presented at the meeting from the phase 1/2a FONTANA trial (NCT05797168) demonstrated confirmed ORRs of 61.7% (95% CI, 48.2%-73.9%) and 48.1% (95% CI, 28.7%-68.1%) with the FRα-directed ADC torvutatug samrotecan in patients with PROC and FRα-high (n = 60) and FRα-ultralow/null (n = 27) tumors, respectively.

Effective standard options for PROC remain limited despite recent approvals, Backes said. She sees an opportunity to use these agents earlier, including in patients who are technically platinum sensitive but may have lost that sensitivity after progression on a PARP inhibitor. Open questions include whether to give ADCs as maintenance or reserve them for recurrence, and how to balance toxicity. Given their single-agent activity, she questioned whether combinations, such as with bevacizumab (Avastin), will add much.

Myelosuppression is a key practical concern with topoisomerase 1 inhibitor–based ADCs. At 5.8 mg/kg in BEHOLD-1, neutropenia occurred in 87% of patients (grade ≥3, 60%), and grade 3 or higher treatment-related adverse effects occurred in 71% vs 49% at 4.8 mg/kg and 22% at 2.8 mg/kg; 1 patient (2%) at 5.8 mg/kg discontinued because of a treatment-related adverse effect. Granulocyte colony-stimulating factor prophylaxis is now strongly recommended across the BEHOLD program. Backes noted that giving granulocyte colony-stimulating factor every 3 weeks carries its own adverse effects and raises questions about long-term effects on bone marrow.Floor Backes, MD, director of the Division of Gynecologic Oncology, a board-certified gynecologic oncologist, and a tenured professor at The Ohio State University Wexner Medical Center and the Ohio State University Comprehensive Cancer Center–James, discussed updated findings 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), as well as where ADCs may fit in ovarian cancer care and the practical challenges of using them.