Ubamatamab

Shows activity

Also known as:

REGN4018

Cancer types include:

ovarian cancer uterine cancer

HealthScout AI Analysis

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Overview

Ubamatamab (REGN4018) is an investigational, IgG-like bispecific T‑cell–engaging antibody being developed by Regeneron for MUC16‑expressing solid tumors, particularly recurrent ovarian cancer; phase 1/2 development is ongoing with randomized phase 2 expansion cohorts opened in 2024 and additional cohorts in MUC16+ endometrial cancer. (pubmed.ncbi.nlm.nih.gov)

Mechanism of action

Target: Bridges MUC16 on tumor cells to CD3 on T cells, triggering local T‑cell activation and cytotoxicity. Binding and activity were minimally affected by soluble CA‑125 (shed MUC16) in preclinical testing. (pubmed.ncbi.nlm.nih.gov)
Preclinical data: Demonstrated MUC16‑directed T‑cell activation and antitumor activity in xenograft and humanized murine models; was well tolerated in cynomolgus monkeys. Anti–PD‑1 co‑treatment enhanced activity in vivo, informing clinical combination with cemiplimab. (pubmed.ncbi.nlm.nih.gov)

Clinical development

Ongoing phase 1/2 trial (NCT03564340) evaluates ubamatamab alone and with cemiplimab in recurrent ovarian cancer and in MUC16+ endometrial cancer. The phase 2 part includes randomized cohorts testing ubamatamab 250 mg or 800 mg IV every 3 weeks (Q3W) with step‑up priming, and a combination arm with cemiplimab 350 mg Q3W. (oncologypro.esmo.org)

Efficacy

Early, nonrandomized phase 1 dose‑escalation results (conference presentations) in heavily pretreated recurrent ovarian cancer:

Monotherapy (ESMO 2022/ESMO Gynaecological Cancers 2023, n=78 treated; efficacy set n=42 who received ≥1 full dose ≥20 mg):
Objective response rate (ORR): 14.3% (95% CI 5.4–28.5).
Disease control rate (DCR): 57.1% (41.0–72.3).
Median duration of response (DoR): 12.2 months.
Exploratory subsets: ORR 20.7% without baseline visceral metastases (n=29) and 30.8% in high MUC16 expression (n=13). (oncologypro.esmo.org)
Combination with cemiplimab (ESMO 2023 dose‑escalation; 22 patients who received ≥1 dose of cemiplimab):
ORR: 18.2% (95% CI 5.2–40.3).
Median DoR: 8.3 months (95% CI 4.2–not estimable).
CA‑125 response: 22.7% (95% CI 7.8–45.4).
6‑ and 12‑mo PFS rates: 47.6% and 23.8%, respectively. (oncologypro.esmo.org)

Note: As of October 2025, randomized phase 2 results have not yet been reported publicly; the trial remains ongoing. (fdaaa.trialstracker.net)

Safety

Monotherapy (phase 1 dose escalation): Most common treatment‑emergent adverse events (TEAEs) were pain (87%) and cytokine release syndrome (CRS; 73%, all grade 1–2), mainly during weeks 1–2 of step‑up dosing. Common grade ≥3 TEAEs included anemia (~23–24%) and abdominal pain (~19–21%). No clear dose–response relationship in safety from 20–800 mg. (oncologypro.esmo.org)
Combination with cemiplimab: Similar TEAE profile with pain (83%) and CRS (69%, all grade 1–2) most frequent; grade ≥3 events included anemia (26%), pain (20%), and neutropenia (11%). A grade 4 haemophagocytic lymphohistiocytosis (HLH) case occurred at a higher ubamatamab dose (450 mg) during escalation. Ubamatamab PK was not impacted by cemiplimab. (oncologypro.esmo.org)

Step‑up dosing is used to mitigate CRS risk in both monotherapy and combination regimens, and phase 2 employs Q3W maintenance dosing after the priming phase. (oncologypro.esmo.org)

Trial access and status

Master phase 1/2 trial: NCT03564340; actively enrolling expansion cohorts (multiple U.S. sites). (dana-farber.org)
Additional disease‑specific exploration includes a phase 2 study in MUC16‑expressing SMARCB1‑deficient malignancies (NCT06444880; initiated Oct 2024). (fdaaa.trialstracker.net)

Active trials using Ubamatamab

Found 3 active trials using this drug:

Multi-arm Phase 2 Study of Ubamatamab (REGN4018; MUC16×CD3 Bispecific Antibody) With or Without Additional Agents in Platinum-Resistant Ovarian Cancer

Sponsor: Regeneron Pharmaceuticals (industry) Phase: 2 Start date: May 28, 2025

HealthScout AI summary: Adults with platinum‑resistant high‑grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer (ECOG 0–1) are randomized to ubamatamab (MUC16×CD3 T‑cell–redirecting bispecific) with prophylactic sarilumab, given alone or combined with bevacizumab, cemiplimab plus fianlimab (PD‑1/LAG‑3 blockade), or pegylated liposomal doxorubicin. Excludes clear cell/mucinous/carcinosarcoma histologies and active CNS disease; primary endpoint is RECIST ORR.

ClinicalTrials.gov ID: NCT06787612

A Phase 1/2 Study of REGN5668 (MUC16xCD28, a Costimulatory Bispecific Antibody) Administered in Combination With Other Agents in MUC16 + Malignancies

Sponsor: Regeneron Pharmaceuticals (industry) Phase: 1/2 Start date: Dec. 8, 2020

HealthScout AI summary: Adults with MUC16-positive advanced ovarian, primary peritoneal/fallopian tube, or endometrial cancer after prior platinum (and prior anti–PD‑1 for endometrial) receive the investigational MUC16×CD28 costimulatory bispecific REGN5668 alone or combined with anti–PD‑1 cemiplimab, cemiplimab+anti–LAG‑3 fianlimab, or the MUC16×CD3 T‑cell engager ubamatamab (some cohorts with IL‑6R blocker sarilumab for CRS mitigation). Aims to enhance T‑cell activation against MUC16 tumors via CD28 costimulation with or without PD‑1/LAG‑3 blockade or CD3 engagement; key exclusions include prior MUC16‑targeted therapy, active autoimmune/CNS disease, and significant cardiac disease.

ClinicalTrials.gov ID: NCT04590326

A Phase 1/2 Study of REGN4018 (Ubamatamab), a MUC16×CD3 Bispecific Antibody, Administered Alone or in Combination With Cemiplimab in Patients With Recurrent Ovarian Cancer or Other Recurrent MUC16+ Cancers

Sponsor: Regeneron Pharmaceuticals (industry) Phase: 1/2 Start date: May 21, 2018

HealthScout AI summary: Adults with recurrent epithelial ovarian, primary peritoneal, fallopian tube, or other MUC16-positive cancers (including MUC16+ endometrial) after prior platinum therapy and without standard options; a randomized cohort targets platinum‑resistant ovarian cancer after 2–4 prior lines. Investigational therapy is ubamatamab, a MUC16×CD3 T cell–engaging bispecific antibody, given IV as monotherapy or combined with the anti–PD‑1 antibody cemiplimab.

ClinicalTrials.gov ID: NCT03564340