Clinical trial NCT04590326: A Trial to Find Out How Safe REGN5668 is and How Well it Works When Given With Either Cemiplimab or REGN4018
Official title: Phase 1/2 Study of REGN5668 (MUC16xCD28, a Costimulatory Bispecific) Administered in Combination With Cemiplimab or REGN4018 (MUC16xCD3)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Cancer
Endometrial Cancer
Keywords: Progressive
Recurrent
Refractory
Serum CA-125 levels >= 2x ULN
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-10-19
Enrollment: 612
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study is researching an investigational drug called REGN5668. Participants will receive additional investigational drugs in combination with REGN5668. These additional drugs include cemiplimab or REGN4018 (with or without sarilumab).

The main purposes of this study are to:

* Learn about the safety and profile of any side effects from the study drugs and to determine the highest, safe dose that can be given to participants with ovarian cancer or cancer of the uterus
* Look for signs that the study drugs can treat ovarian cancer or cancer of the uterus

This study has 2 parts. The purpose of Part 1 (Escalation) to find the highest, safe dose of the study drug(s). The purpose of Part 2 (Expansion) is to use the doses chosen in Part 1. Participants with cancer of the uterus will only participate in Part 2.

The study is looking at several other research questions, including:

* Side effects that may be experienced by participants taking REGN5668 alone and/or in combination with cemiplimab or REGN4018
* How REGN5668 works in the body either alone and/or in combination with cemiplimab or REGN4018
* How much of the study drugs (REGN5668, cemiplimab, REGN4018) are in the blood
* To see if REGN5668 in combination with cemiplimab or REGN4018 works to treat cancer
* To find out how safe, tolerable, and effective in mitigating Cytokine Release Syndrome (CRS) sarilumab pretreatment is when given before REGN4018


Eligibility criteria: Key Inclusion Criteria:

1. Ovarian Cancer Cohorts Only: Has histologically or cytologically confirmed diagnosis of advanced epithelial ovarian cancer (except carcinosarcoma), primary peritoneal, or fallopian tube cancer that has received at least 1 line of platinum-based systemic therapy as defined in the protocol
2. Expansion cohorts only: Has at least 1 lesion that is measurable by RECIST 1.1 as described in the protocol.
3. Has a serum CA-125 level ≥2x ULN (in screening, not applicable to endometrial cohorts)
4. Has adequate organ and bone marrow function as defined in the protocol
5. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Has a life expectancy of at least 3 months
7. Endometrial Cancer Cohorts Only: histologically confirmed endometrial cancer that has progressed or recurrent after prior anti-PD-1 therapy and platinum-based chemotherapy as described in the protocol

Key Exclusion Criteria:

1. Prior anti-cancer immunotherapy as defined in the protocol
2. Recent treatment with anti-Programmed Cell Death (PD-1)/PDL-1 therapy
3. Has had another malignancy within the last 5 years that is progressing, requires active treatment, or has a high likelihood of recurrence as defined in the protocol
4. Prior treatment with a MUC16-targeted therapy
5. Expansion cohorts only: More than 4 prior lines of cytotoxic chemotherapy (including antibody drug conjugates)
6. Has any condition that requires ongoing/continuous corticosteroid therapy as defined in the protocol within 1 week prior to the first dose of study drug
7. Has ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments as defined in the protocol
8. Has untreated or active primary brain tumor, CNS metastases, leptomeningeal disease, or spinal cord compression as defined in the protocol
9. Has history of clinically significant cardiovascular disease as defined in the protocol
10. Has known allergy or hypersensitivity to cemiplimab and/or components of study drug(s).

Note: Other protocol-defined Inclusion/Exclusion criteria apply

Primary outcomes:
measure: Incidence of dose limiting toxicities (DLT)
timeFrame: 42 days
measure: Incidence of DLTs
timeFrame: 21 days post combination administration
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Through study completion, up to 5 years
measure: Incidence of serious adverse events (SAEs)
timeFrame: Through study completion, up to 5 years
measure: Incidence of deaths
timeFrame: Through study completion, up to 5 years
measure: Incidence of laboratory abnormalities (Grade 3 or higher per National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 5.0 [v5.0])
timeFrame: Through study completion, up to 5 years
measure: Concentrations of REGN5668 in serum when dosed alone and in combination with cemiplimab or REGN4018
timeFrame: Through study completion, up to 5 years
measure: ORR defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Eisenhauer, 2009) in combination with cemiplimab or REGN4018 (separately by cohort and combination)
timeFrame: Through study completion, up to 5 years
Secondary outcomes:
measure: Concentration of REGN4018 in serum over time
timeFrame: Through study completion, up to 5 years
measure: Concentration of cemiplimab in serum over time
timeFrame: Through study completion, up to 5 years
measure: ORR based on Immune-based therapy RECIST (iRECIST)
timeFrame: Through study completion, up to 5 years
measure: BOR based on RECIST 1.1 and iRECIST
timeFrame: Through study completion, up to 5 years
measure: DOR based on RECIST 1.1 and iRECIST
timeFrame: Through study completion, up to 5 years
measure: DCR based on RECIST 1.1 and iRECIST
timeFrame: Through study completion, up to 5 years
measure: PFS based on RECIST 1.1 and iRECIST
timeFrame: Through study completion, up to 5 years
measure: CA-125 change from baseline after treatment with REGN5668 in combinations with cemiplimab or REGN4018 (separately by cohort and combination)
timeFrame: Through study completion, up to 5 years
measure: Presence or absence of anti-drug antibodies against REGN5668
timeFrame: Through study completion, up to 5 years
measure: Presence or absence of anti-drug antibodies against REGN4018
timeFrame: Through study completion, up to 5 years
measure: Presence or absence of anti-drug antibodies against cemiplimab
timeFrame: Through study completion, up to 5 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Irvine
country: United States
facility: The City of Hope Orange County Lennar Foundation Cancer Center
state: California
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center of Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute Brookline Avenue
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Perelman School of Medicine at the University of Pennsylvania
state: Pennsylvania
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance at South Lake Union - G3630
state: Washington
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven
state: Vlaams Brabant
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
state: Bourgogne
city: Pierre-Benite
country: France
facility: Hopital Lyon Sud
state: Lyon
city: Caen
country: France
facility: Centre Francois Baclesse (CFB)
state: Normandy
city: Bordeaux
country: France
facility: Institut Bergonie
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario Santiago de Compostela
state: A Coruna
city: Girona
country: Spain
facility: Institut Catala dOncologia Girona
city: Madrid
country: Spain
facility: Ciudad Universitaria
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre Universidad Complutense de Madrid UCM
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: