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

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Endometrial Cancer; Recurrent Primary Peritoneal Cancer; Recurrent Ovarian Cancer; Recurrent Endometrial Cancer; Recurrent Fallopian Tube Cancer; Low-grade Serous Ovarian Cancer

Treatments: Drug: Sarilumab; Drug: Ubamatamab; Drug: Tocilizumab; Drug: Cemiplimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03564340

R4018-ONC-1721

2019-003298-24 (EudraCT Number)

2024-510783-23-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

The main purpose of this study is to:

• Learn about the safety of ubamatamab and to find out what dose of ubamatamab can be given alone or with cemiplimab to patients with ovarian cancer or cancer of the uterus
• The study will also look at the levels of ubamatamab and/or cemiplimab in the body and measure how well the body can remove the study drug(s). This is called pharmacokinetics
• The study will also look at any signs that ubamatamab alone or with cemiplimab can treat recurrent advanced ovarian cancer or cancer of the uterus
• To find out how safe and tolerable pretreatment is in combination with ubamatamab and to see how well it works to prevent or minimize Cytokine Release Syndrome (CRS)

Enrollment: 890 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Ovarian Cancer Cohorts Only: Patients with histologically or cytologically confirmed diagnosis of advanced, epithelial ovarian cancer (except carcinosarcoma), primary peritoneal, or fallopian tube cancer who have all of the following:

   1. serum CA-125 level ≥2 x upper limit of normal (ULN) (in screening, not required for low-grade serous carcinoma)
   2. has received at least 1 line of platinum-containing therapy or must be platinum-intolerant (applicable for dose escalation and non-randomized dose expansion cohorts)
   3. documented relapse or progression on or after the most recent line of therapy
   4. no standard therapy options likely to convey clinical benefit

2. Adequate organ and bone marrow function as defined in the protocol

3. Life expectancy of at least 3 months

4. Randomized phase 2 expansion cohort (Ovarian Cancer only): Platinum-resistant ovarian cancer patients who have had 2 to 4 lines of platinum-based therapy as defined in the protocol.

5. Endometrial Cancer Cohorts Only: histologically confirmed endometrial cancer that has progressed or recurrent after prior anti-Programmed Cell Death Ligand 1 (PD-1) therapy and platinum-based chemotherapy:

   1. MUC16 positivity of tumor cells ≥25% by immunohistochemistry (IHC), as defined in the protocol
   2. 1-4 prior lines of systemic therapy, as described in the protocol

Key Exclusion Criteria:

1. Prior treatment with anti-Programmed Cell Death (PD-1)/PD-L1 therapy, as described in the protocol
2. Ovarian Cancer Expansion cohorts only: More than 4 prior lines of cytotoxic chemotherapy (does not apply to low-grade serous ovarian cancer cohort)
3. Prior treatment with a MUC16 - targeted therapy
4. Untreated or active primary brain tumor, central nervous system (CNS) metastases, or spinal cord compression, as described in the protocol
5. History and/or current cardiovascular disease, as defined in the protocol
6. Severe and/or uncontrolled hypertension at screening. Patients taking anti-hypertensive medication must be on a stable anti-hypertensive regimen

Note: Other protocol-defined Inclusion/Exclusion Criteria apply

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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890 participants in 2 patient groups

Monotherapy

Experimental group

Description:

REGN4018 administration

Treatment:

Drug: Tocilizumab

Drug: Ubamatamab

Drug: Sarilumab

Combination Therapy

Experimental group

Description:

REGN4018 and cemiplimab administration

Treatment:

Drug: Cemiplimab

Drug: Ubamatamab