What safety findings were reported?
Safety was assessed in all 19 patients in the LGSOC subset. Treatment-emergent adverse events (TEAEs) occurred in 100% of patients, and cytokine release syndrome occurred in 90% (n = 17), all grade 1 or 2.¹ Serious TEAEs of grade 3 or higher occurred in 21% of patients (n = 4). Treatment-related adverse events (TRAEs) occurred in 74% (n = 14).
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).¹ Notably, most AEs occurred during the step-up dosing period. One patient discontinued treatment because of a stroke considered unrelated to ubamatamab, and no TEAEs resulted in death.
How does ubamatamab fit into the LGSOC treatment landscape?
LGSOC is biologically distinct from high-grade serous ovarian cancer (HGSOC), accounts for up to 10% of serous ovarian cancer, and typically has uniformly high MUC16 expression. It often affects younger women and grows more slowly than HGSOC, but it frequently recurs and responds poorly to conventional chemotherapy. According to the release, in recurrent advanced LGSOC, historical ORRs with chemotherapy and endocrine therapy generally remain below 15% in recurrent advanced disease.
Ubamatamab is designed to bridge MUC16 on cancer cells with CD3-expressing T cells to facilitate local T-cell activation.
What is the ubamatamab trial design, and what is next?
The ongoing, open-label phase 1/2 trial is evaluating ubamatamab alone and in combination with cemiplimab in adults with recurrent platinum-resistant ovarian cancer and other recurrent MUC16-expressing cancers.2 Phase 1 primarily assessed safety, tolerability, dose-limiting toxicities, and pharmacokinetics, with efficacy as a secondary end point; phase 2 is evaluating antitumor activity, primarily ORR, while continuing to assess safety.
Eligible patients for the ovarian cancer cohorts of the trial had histologically or cytologically confirmed diagnoses of the disease including a serum CA-125 level at least 2 times the upper limit of normal, 1 prior line of platinum-containing therapy or platinum intolerant status, documented relapse or progression on or after most recent line of therapy, and no standard therapy options likely to convey clinical benefit.2 The randomized phase 2 expansion cohort will enroll patients with platinum-resistant ovarian cancer who have received 2 to 4 lines of platinum-based therapy.
A prospective, potentially registrational cohort in the trial is evaluating ubamatamab at 800 mg every 3 weeks in up to 100 patients with recurrent LGSOC and is currently enrolling. Regeneron plans to discuss the data with the FDA in the coming months, in addition to initiating a randomized, controlled phase 3 trial to support use in LGSOC.
References
- 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 5, 2026. https://tinyurl.com/4v37z2p5
- 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. Updated September 25, 2026. Accessed October 5, 2026. https://tinyurl.com/bdhncms8
