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

Phase 2RecruitingNCT03564340

Regeneron Pharmaceuticals890 enrolled

Overview

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)

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

890

Conditions

Recurrent Ovarian Cancer Recurrent Fallopian Tube Cancer Recurrent Primary Peritoneal Cancer Recurrent Endometrial Cancer

Interventions

UbamatamabDRUG

Administered per the protocol

CemiplimabDRUG

Administered per the protocol

SarilumabDRUG

Administered per the protocol

TocilizumabDRUG

Administered per the protocol

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (51)

University of Alabama_6th Ave

Birmingham, Alabama, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

RECRUITING

Dana Farber / Harvard Cancer Center

Boston, Massachusetts, United States

RECRUITING

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Outcomes

Primary Outcomes

Number of participants with Dose-limiting toxicity (DLTs) for ubamatamab monotherapy

Dose Escalation Phase

Time frame: From Cycle 1, Day 1 up to 35 days

Number of participants with DLTs for ubamatamab with cemiplimab

Dose Escalation Phase

Time frame: From Cycle 2, Day 1 up to 21 days

Number of participants with Treatment-emergent adverse event (TEAE)s (including immune-related adverse events (imAEs)) for ubamatamab monotherapy

Dose Escalation Phase

Time frame: Up to 2 years

Number of participants with TEAEs (including imAEs) for ubamatamab with cemiplimab

Dose Escalation Phase

Time frame: Up to 2 years

Number of participants with serious adverse events (SAEs) for ubamatamab monotherapy

Dose Escalation Phase

Time frame: Up to 2 years

Number of participants with SAEs for ubamatamab with cemiplimab

Dose Escalation Phase

Time frame: Up to 2 years

Number of deaths for ubamatamab monotherapy

Dose Escalation Phase

Time frame: Up to 2 years

Number of deaths for ubamatamab with cemiplimab

Dose Escalation Phase

Time frame: Up to 2 years

Number of participants with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) for ubamatamab monotherapy

Dose Escalation Phase

Time frame: Up to 2 years

Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for ubamatamab with cemiplimab

Dose Escalation Phase

Time frame: Up to 2 years

Concentration of ubamatamab in serum over time for ubamatamab monotherapy

Dose Escalation Phase

Time frame: Up to 2 years

Concentration of ubamatamab in serum over time for ubamatamab with cemiplimab

Dose Escalation Phase

Time frame: Up to 2 years

Objective response rate (ORR) defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for ubamatamab monotherapy

Dose Expansion Phase

Time frame: Up to 2 years

ORR defined by RECIST 1.1 for ubamatamab with cemiplimab

Dose Expansion Phase

Time frame: Up to 2 years

Secondary Outcomes

ORR based on RECIST 1.1 for ubamatamab monotherapy

Dose Escalation Phase

Time frame: Up to 2 years

ORR based on RECIST 1.1 for ubamatamab with cemiplimab

Dose Escalation Phase

Time frame: Up to 2 years

Number of participants with TEAEs (including imAEs) for ubamatamab monotherapy

Dose Expansion Phase

Time frame: Up to 2 years

Number of participants with TEAEs (including imAEs) for ubamatamab with cemiplimab

Dose Expansion Phase

Time frame: Up to 2 years

Number of participants with SAEs for ubamatamab monotherapy

Dose Expansion Phase

Time frame: Up to 2 years

Number of participants with SAEs for ubamatamab with cemiplimab

Dose Expansion Phase

Time frame: Up to 2 years

Number of deaths for ubamatamab monotherapy

Dose Expansion Phase

Time frame: Up to 2 years

Number of deaths for ubamatamab with cemiplimab

Dose Expansion Phase

Time frame: Up to 2 years

Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for ubamatamab monotherapy

Dose Expansion Phase

Time frame: Up to 2 years

Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for ubamatamab with cemiplimab

Central Contacts

Clinical Trials Administrator

CONTACT

844-734-6643 clinicaltrials@regeneron.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Roswell Park Cancer Institute

Buffalo, New York, United States

WITHDRAWN

Columbia University Medical Center

New York, New York, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

RECRUITING

The Ohio State University Wexner Medical Center James Comprehensive Cancer Center

Hilliard, Ohio, United States

RECRUITING

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, United States

RECRUITING

...and 41 more locations

Dose Expansion Phase

Time frame: Up to 2 years

Concentration of ubamatamab in serum over time for ubamatamab monotherapy

Dose Expansion Phase

Time frame: Up to 2 years

Concentration of ubamatamab in serum over time for ubamatamab with cemiplimab

Dose Expansion Phase

Time frame: Up to 2 years

Change from baseline in quality of life (QoL) as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 GHS/QoL score for ubamatamab monotherapy

Dose Expansion Phase The EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social) , symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."

Time frame: Baseline up to 2 years

Dose Expansion Phase

Time frame: Baseline up to 2 years

Change from baseline in physical functioning as measured by the EORTC QLQ-C30 physical functioning score for ubamatamab monotherapy

Dose Expansion Phase

Time frame: Baseline up to 2 years

Change from baseline in physical functioning as measured by the EORTC QLQ-C30 physical functioning score for ubamatamab with cemiplimab

Dose Expansion Phase

Time frame: Baseline up to 2 years

Change from baseline in abdominal symptoms as measured by the Measure of Ovarian Symptoms and Treatment (MOST)-Abdominal index score for ubamatamab monotherapy

Dose Expansion Phase excluding the Endometrial Cancer Cohort The MOST-24 is a 24-item questionnaire used to measure the impact of chemotherapy on symptoms (21 items) and well-being (3 items). The expected questionnaire completion time is less than 5 minutes. The prevalence of each MOST item at assessment time points can be summarized by providing the mean, standard deviation and proportions based on the MOST response format, a numeric rating scale with integers from zero to 10, with five verbal anchors: 'No trouble at all' (0), 'Mild' (1-3), 'Moderate' (4-6), 'Severe' (7-10), and 'Worst I can imagine' (10).

Time frame: Baseline up to 2 years

Change from baseline in abdominal symptoms as measured by the MOST-Abdominal index score for ubamatamab with cemiplimab

Dose Expansion Phase Not applicable to Endometrial Cancer Cohort

Time frame: Baseline up to 2 years

Time to deterioration in GHS/QoL for ubamatamab monotherapy

Dose Expansion Phase

Time frame: Up to 2 years

Time to deterioration in GHS/QoL for ubamatamab with cemiplimab

Dose Expansion Phase

Time frame: Up to 2 years

Time to deterioration in physical functioning for ubamatamab monotherapy

Dose Expansion Phase

Time frame: Up to 2 years

Time to deterioration in physical functioning for ubamatamab with cemiplimab

Dose Expansion Phase

Time frame: Up to 2 years

Time to deterioration in abdominal symptoms for ubamatamab monotherapy

Dose Expansion Phase

Time frame: Up to 2 years

Time to deterioration in abdominal symptoms for ubamatamab with cemiplimab

Dose Expansion Phase

Time frame: Up to 2 years

Change from baseline in QoL as measured by EQ-5D for ubamatamab monotherapy

Dose Expansion Phase

Time frame: Baseline up to 2 years

Change from baseline in QoL as measured by EQ-5D for ubamatamab with cemiplimab

Dose Expansion Phase

Time frame: Baseline up to 2 years

ORR based on iRECIST for ubamatamab monotherapy