Regeneron’s investigational ubamatamab showed a 73% objective response rate in 11 patients with advanced LGSOC treated with 800 mg monotherapy.
Written By: Neha Vishwakarma, PharmD
Reviewed By: Pharmacally Editorial Team
Regeneron Pharmaceuticals has announced the first clinical results for ubamatamab, an investigational MUC16×CD3 bispecific antibody, in patients with advanced low-grade serous ovarian cancer (LGSOC). The data were presented in a late-breaking plenary oral session at the International Gynecologic Cancer Society (IGCS) 2026 Annual Global Meeting.
The results come from an ongoing Phase 1/2 study (NCT03564340) evaluating ubamatamab alone and in combination with Libtayo (cemiplimab) in patients with recurrent platinum-resistant ovarian cancer and other recurrent MUC16-expressing cancers. Ubamatamab is designed to bridge MUC16 expressed on cancer cells with CD3-expressing T cells, enabling T-cell engagement and activation against tumor cells.
LGSOC Remains a Distinct and Difficult-to-Treat Ovarian Cancer
LGSOC is a biologically distinct subtype of serous ovarian cancer that accounts for as much as 10% of serous ovarian cancers. The disease typically shows high MUC16 expression and often affects younger women.
Compared with high-grade serous ovarian cancer (HGSOC), LGSOC generally grows more slowly but frequently recurs and has limited sensitivity to conventional chemotherapy. Regeneron cites median overall survival of approximately seven years from diagnosis for LGSOC compared with about four years for HGSOC.
In recurrent advanced LGSOC, historical studies have generally reported objective response rates below 15% with chemotherapy and endocrine therapy. Regeneron also noted that the only approved therapy has produced a 44% ORR in biomarker-selected patients, who represent approximately 30% of the overall LGSOC population.
Phase 1/2 Study Evaluates Ubamatamab in Recurrent Disease
The ongoing open-label Phase 1/2 study is evaluating intravenous ubamatamab as monotherapy and in combination with cemiplimab in adults with recurrent platinum-resistant ovarian cancer and other recurrent MUC16-expressing cancers.
Phase 1 primarily evaluated safety, tolerability, dose-limiting toxicities and pharmacokinetics, while Phase 2 is evaluating antitumor activity, primarily through objective response rate.
The IGCS presentation focused on 19 patients with LGSOC, who had received a median of four prior lines of therapy. Patients received ubamatamab at doses ranging from 3 mg to 800 mg, administered weekly or every three weeks, either as monotherapy or in combination with cemiplimab.
The reported efficacy analysis focused specifically on 11 patients who received 800 mg ubamatamab monotherapy. Of these, eight received weekly dosing and three received dosing every three weeks.
73% Objective Response Rate Reported at 800 mg
Among the 11 patients treated with 800 mg ubamatamab monotherapy, the objective response rate was 73% (95% CI, 39.0–94.0%). All reported responses were partial responses.
The median duration of response was 9 months (95% CI, 6.9 months to not estimable), based on the Kaplan-Meier estimate.
Median progression-free survival was 11 months (95% CI, 3.0 months to not estimable), also based on the Kaplan-Meier estimate.
Because the efficacy analysis included only 11 patients, the 73% ORR should be interpreted as an early clinical signal rather than a definitive estimate of treatment activity in the broader LGSOC population.
Safety Findings in 19 Patients
Safety was assessed across all 19 patients in the LGSOC subset, rather than only the 11 patients included in the 800 mg monotherapy efficacy analysis.
Treatment-emergent adverse events occurred in all 19 patients. Cytokine release syndrome (CRS) occurred in 90% of patients (17/19), with all reported cases being Grade 1 or Grade 2.
Serious treatment-emergent adverse events of Grade 3 or higher occurred in 21% of patients (4/19), while treatment-related adverse events occurred in 74% (14/19).
Grade 3 or higher treatment-related adverse events included:
- Neutropenia: 21%
- Anemia: 11%
- Increased alanine aminotransferase (ALT): 11%
- Increased aspartate aminotransferase (AST): 11%
- Abdominal pain: 5%
- Ileus: 5%
Most adverse events occurred during the step-up dosing period. One participant discontinued treatment because of a stroke considered unrelated to ubamatamab. No treatment-emergent adverse events resulted in death.
Regeneron Plans a Dedicated LGSOC Cohort
Regeneron is currently enrolling a prospective, dedicated, potentially registrational Phase 2 cohort evaluating ubamatamab 800 mg monotherapy administered every three weeks in up to 100 patients with recurrent LGSOC.
The company said it plans to discuss the emerging data with the U.S. Food and Drug Administration (FDA) in the coming months. Regeneron also plans to initiate a confirmatory randomized controlled Phase 3 trial intended to support the potential use of ubamatamab in LGSOC.
Ubamatamab remains investigational. Its potential uses have not been approved, and no regulatory authority has evaluated its safety or efficacy.
Early Results Require Longer Follow-Up
The reported findings provide an early clinical signal for ubamatamab in heavily pretreated LGSOC, but the efficacy dataset remains small.
The 73% ORR was observed in only 11 patients, resulting in a wide 95% confidence interval of 39.0% to 94.0%. The median PFS estimate also has a broad confidence interval, with a lower bound of 3.0 months and an upper bound that was not estimable.
The study is open-label and does not include a randomized comparator. Historical response rates therefore provide context but cannot establish comparative efficacy because differences in patient populations, treatment histories and study designs can affect response outcomes.
The safety findings also require continued evaluation as more patients are treated and followed for longer periods. CRS, neutropenia and liver enzyme elevations were among the reported adverse events in this early dataset.
Path Forward for Ubamatamab
The initial findings support continued clinical evaluation of ubamatamab in LGSOC, particularly through the dedicated Phase 2 cohort using the 800 mg every-three-week regimen.
The planned expansion to up to 100 patients should provide a larger dataset for evaluating response rates, response durability, progression-free survival and safety. The planned randomized Phase 3 study, if initiated, would provide a further assessment of the benefit-risk profile of ubamatamab in recurrent LGSOC.
For now, the reported 73% ORR represents an early finding from a small, heavily pretreated patient population. Longer follow-up and larger controlled studies will be needed to determine whether the observed responses translate into a clinically meaningful and durable treatment benefit for patients with recurrent LGSOC.
Reference
Ubamatamab (MUC16xCD3) Shows a High Rate of Durable Responses in Initial Study of Patients with Advanced Low-Grade Serous Ovarian Cancer (LGSOC), Regeneron, 01 October 2026
Study of REGN4018 (Ubamatamab) Administered Alone or in Combination With Cemiplimab in Adult Patients with Recurrent Ovarian Cancer or Other Recurrent Mucin-16 Expressing (MUC16+) Cancers, ClinicalTrials.gov ID NCT03564340
About the Writer
Neha Vishwakarma (Linkedin) is a Pharm.D professional with experience in clinical pharmacy, pharmacovigilance, and clinical research. She has hands-on experience in ADR assessment, ICSR processing, medication safety, and clinical data evaluation. Her research background in surgical site infections and antibiotic use supports her focus on evidence-based healthcare writing.