Ubamatamab Shows Durable Responses in Low-Grade Serous Ovarian Cancer

Ubamatamab (MUC16xCD3) led to a high rate of durable objective responses in patients with recurrent, heavily pretreated low-grade serous ovarian cancer (LGSOC), according to data from an ongoing phase 1/2 trial (NCT03564340) presented in a late-breaking plenary oral session at the International Gynecologic Cancer Society (IGCS) 2026 Annual Global Meeting.¹

Among 11 patients with LGSOC who received the highest dose of ubamatamab tested in the trial of 800 mg monotherapy, given either weekly (n = 8) or every 3 weeks (n = 3), the bispecific antibody yielded a 73.0% objective response rate (ORR; 95% CI, 39.0%-94.0%), with all responses being partial responses. The median duration of response was 9 months (95% CI, 6.9-not estimable [NE]) and median progression-free survival (PFS) was 11 months (95% CI, 3.0-NE).

“The high rate of durable responses observed thus far with ubamatamab in [LGSOC], without requiring biomarker selection, are highly encouraging and reinforce our excitement about MUC16 as a new therapeutic target in this difficult-to-treat disease,” Israel Lowy, MD, PhD, clinical development unit head of oncology at Regeneron, stated in a news release. “This initial clinical evidence highlights the potential of our bispecific approach to bring a differentiated and first-in-class treatment option to patients in need.”

Trial Design

LGSOC is biologically distinct from high-grade serous ovarian cancer, making up to 10% of serous ovarian cancer cases and typically characterized by uniformly high MUC16 expression.¹ Ubamatamab is an MUC16xCD3 bispecific antibody that bridges MUC16, or Mucin 16, on cancer cells with CD3-expressing T cells to promote local T-cell activation. Preclinical findings including mouse and monkey models provided translational pharmacokinetic data and contributed to the development of first-in-human dose escalation with step-up dosing starting at 0.1 mg to manage cytokine release syndrome.²

The data come from an ongoing, open-label phase 1/2 trial evaluating ubamatamab alone and in combination with cemiplimab (Libtayo) in adult patients with recurrent platinum-resistant ovarian cancer and other recurrent MUC16-expressing cancers. The phase 1 portion is primarily assessing safety, tolerability, dose-limiting toxicities, and pharmacokinetics, with efficacy evaluated as a secondary end point; the phase 2 portion is evaluating anti-tumor activity, primarily via ORR, while continuing to assess safety.¹

The LGSOC-specific data presented at IGCS came from a subset of 19 patients who had received a median of 4 prior lines of therapy and received doses of ubamatamab ranging from 3 to 800 mg, administered intravenously once weekly or every 3 weeks, as monotherapy or in combination with cemiplimab.

Safety Findings

Treatment-emergent adverse events (TEAEs) occurred in 100% of the 19 assessed patients. Serious TEAEs of grade 3 or higher occurred in 21% of patients (n = 4), and treatment-related adverse events (TRAEs) occurred in 74% (n = 14). Cytokine release syndrome occurred in 90% of patients (n = 17), all grade 1 or 2. Grade 3 or higher TRAEs included neutropenia (21%; n = 4), anemia (11%; n = 2), increased alanine aminotransferase (11%; n = 2), increased aspartate aminotransferase (11%; n = 2), abdominal pain (5%; n = 1), and ileus (5%; n = 1). Most adverse events occurred during step-up dosing. No TEAEs led to death, although 1 patient discontinued treatment due to a stroke deemed unrelated to ubamatamab.

Clinical Implications and Next Steps

The news release compared the outcome favorably with historical trial data for chemotherapy or endocrine therapy that generally show ORRs below 15%, as well as vs the only approved therapy for the disease, avutometinib plus defactinib (Avmapki Fakzynja Co-pack), which resulted in an ORR of 44% specifically in a KRAS-mutant population.^1,3

Based on these preliminary results, patients are being enrolled in a single-arm, potentially registrational cohort evaluating ubamatamab at 800-mg monotherapy every 3 weeks in up to 100 patients with recurrent LGSOC.¹ The company said it plans to discuss the data with the FDA in the coming months, and is also planning a confirmatory, randomized, controlled phase 3 trial to support ubamatamab's use in LGSOC.

“We are pleased with the safety profile of the drug as well and are eager to build on these findings through our ongoing trial and planned confirmatory phase 3 trial,” Lowy said in the news release.

REFERENCES

1. Ubamatamab (MUC16xCD3) Shows a High Rate of Durable Responses in Initial Study of Patients with Advanced Low-Grade Serous Ovarian Cancer (LGSOC). News release. Regeneron Pharmaceuticals, Inc. October 1, 2026. Accessed October 2, 2026. https://tinyurl.com/2xwbbz3a

2. Zhu M, Madia P, Crawford A, et al. Translational findings support regimen selection for first-in-human study of ubamatamab (MUC16 × CD3 bispecific antibody) in patients with recurrent ovarian cancer. Clin Transl Sci. 2024;17(12):e70082. doi:10.1111/cts.70082

3. FDA grants accelerated approval to the combination of avutometinib and defactinib for KRAS-mutated recurrent low-grade serous ovarian cancer. FDA. May 8, 2025. Accessed October 1, 2026. https://tinyurl.com/yw87eyvm