A Trial to Find Out How Safe REGN5668 is and How Well it Works When Given With Either Cemiplimab or REGN4018

• ClinicalTrials.gov Identifier: NCT04590326
• Recruitment Status: Recruiting
• First Posted: October 19, 2020
• Last Update Posted: March 19, 2024
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Tracking Information

• First Submitted Date: October 9, 2020
• First Posted Date: October 19, 2020
• Last Update Posted Date: March 19, 2024
• Actual Study Start Date: December 9, 2020
• Estimated Primary Completion Date: April 27, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 15, 2024)

• Incidence of dose limiting toxicities (DLT) [ Time Frame: 42 days ]
  Dose escalation phase, Module 1
• Incidence of DLTs [ Time Frame: 21 days post combination administration ]
  Dose escalation phase, Module 2
• Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Through study completion, up to 5 years ]
  Primary: Dose escalation phase Secondary: Dose expansion phase
• Incidence of serious adverse events (SAEs) [ Time Frame: Through study completion, up to 5 years ]
  Primary: Dose escalation phase Secondary: Dose expansion phase
• Incidence of deaths [ Time Frame: Through study completion, up to 5 years ]
  Primary: Dose escalation phase Secondary: Dose expansion phase
• 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]) [ Time Frame: Through study completion, up to 5 years ]
  Primary: Dose escalation phase Secondary: Dose expansion phase
• Concentrations of REGN5668 in serum when dosed alone and in combination with cemiplimab or REGN4018 [ Time Frame: Through study completion, up to 5 years ]
  Primary: Dose escalation phase Secondary: Dose expansion phase
• 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) [ Time Frame: Through study completion, up to 5 years ]
  Primary: Dose expansion phase Secondary: Dose escalation phase

Original Primary Outcome Measures (submitted: October 9, 2020)

• Incidence of dose limiting toxicities (DLT) [ Time Frame: 42 days ]
  Dose escalation phase, Module 1
• Incidence of DLTs [ Time Frame: 21 days post combination administration ]
  Dose escalation phase, Module 2
• Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Through study completion, up to 5 years ]
  Primary: Dose escalation phase Secondary: Dose expansion phase
• Incidence of serious adverse events (SAEs) [ Time Frame: Through study completion, up to 5 years ]
  Primary: Dose escalation phase Secondary: Dose expansion phase
• Incidence of deaths [ Time Frame: Through study completion, up to 5 years ]
  Primary: Dose escalation phase Secondary: Dose expansion phase
• 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]) [ Time Frame: Through study completion, up to 5 years ]
  Primary: Dose escalation phase Secondary: Dose expansion phase
• Concentrations of REGN5668 in serum when dosed alone and in combinations with cemiplimab or REGN4018 [ Time Frame: Up to 62 weeks ]
  Primary: Dose escalation phase Secondary: Dose expansion phase
• ORR defined by RECIST 1.1 (Eisenhauer, 2009) in combination with cemiplimab or REGN4018 (separately by cohort and combination) [ Time Frame: Up to 62 weeks ]
  Primary: Dose expansion phase Secondary: Dose escalation phase

Current Secondary Outcome Measures (submitted: March 15, 2024)

• Concentration of REGN4018 in serum over time [ Time Frame: Through study completion, up to 5 years ]
  Dose expansion phase
• Concentration of cemiplimab in serum over time [ Time Frame: Through study completion, up to 5 years ]
  Dose expansion phase
• ORR based on Immune-based therapy RECIST (iRECIST) [ Time Frame: Through study completion, up to 5 years ]
  Dose escalation and expansion phases
• BOR based on RECIST 1.1 and iRECIST [ Time Frame: Through study completion, up to 5 years ]
  Dose escalation and expansion phases
• DOR based on RECIST 1.1 and iRECIST [ Time Frame: Through study completion, up to 5 years ]
  Dose escalation and expansion phases
• DCR based on RECIST 1.1 and iRECIST [ Time Frame: Through study completion, up to 5 years ]
  Dose escalation and expansion phases
• PFS based on RECIST 1.1 and iRECIST [ Time Frame: Through study completion, up to 5 years ]
  Dose escalation and expansion phases
• CA-125 change from baseline after treatment with REGN5668 in combinations with cemiplimab or REGN4018 (separately by cohort and combination) [ Time Frame: Through study completion, up to 5 years ]
  Dose escalation and expansion phases
• Presence or absence of anti-drug antibodies against REGN5668 [ Time Frame: Through study completion, up to 5 years ]
  Dose escalation and expansion phases
• Presence or absence of anti-drug antibodies against REGN4018 [ Time Frame: Through study completion, up to 5 years ]
  Dose escalation and expansion phases
• Presence or absence of anti-drug antibodies against cemiplimab [ Time Frame: Through study completion, up to 5 years ]
  Dose escalation and expansion phases

Original Secondary Outcome Measures (submitted: October 9, 2020)

• Concentration of REGN4018 in serum over time [ Time Frame: Up to 62 weeks ]
  Dose expansion phase
• Concentration of cemiplimab in serum over time [ Time Frame: Up to 62 weeks ]
  Dose expansion phase
• ORR based on iRECIST [ Time Frame: Up to 62 weeks ]
  Dose escalation and expansion phases
• BOR based on RECIST 1.1 and iRECIST [ Time Frame: Up to 62 weeks ]
  Dose escalation and expansion phases
• DOR based on RECIST 1.1 and iRECIST [ Time Frame: Up to 62 weeks ]
  Dose escalation and expansion phases
• DCR based on RECIST 1.1 and iRECIST [ Time Frame: Up to 62 weeks ]
  Dose escalation and expansion phases
• PFS based on RECIST 1.1 and iRECIST [ Time Frame: Up to 62 weeks ]
  Dose escalation and expansion phases
• CA-125 change from baseline after treatment with REGN5668 in combinations with cemiplimab or REGN4018 (separately by cohort and combination) [ Time Frame: Up to 62 weeks ]
  Dose escalation and expansion phases
• Presence or absence of anti-drug antibodies against REGN5668 [ Time Frame: Up to 62 weeks ]
  Dose escalation and expansion phases
• Presence or absence of anti-drug antibodies against REGN4018 [ Time Frame: Up to 62 weeks ]
  Dose escalation and expansion phases
• Presence or absence of anti-drug antibodies against cemiplimab [ Time Frame: Up to 62 weeks ]
  Dose escalation and expansion phases

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)

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

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Ovarian Cancer
• Fallopian Tube Cancer
• Primary Peritoneal Cancer
• Endometrial Cancer

Intervention

• Drug: REGN5668
  REGN5668 will be administered by once weekly intravenous (IV) infusion.
• Drug: Cemiplimab
  For Module 1, after a minimum of a 3-week monotherapy lead-in of REGN5668, cemiplimab will be administered concomitantly every 3 weeks (Q3W) by IV infusion.
  Other Names:

  • REGN2810
  • Libtayo
• Drug: REGN4018
  For Module 2, a 4-5 week monotherapy lead-in of REGN4018 will be administered by once weekly IV infusion. After lead-in, REGN5668 and REGN4018 will be administered concomitantly.
• Drug: Sarilumab
  Administered by IV infusion as prophylaxis for mitigating potential CRS in patients receiving REGN4018

Study Arms

• Experimental: Module 1
  REGN5668 and cemiplimab
  Interventions:

  • Drug: REGN5668
  • Drug: Cemiplimab
• Experimental: Module 2
  REGN5668 and REGN4018
  Interventions:

  • Drug: REGN5668
  • Drug: REGN4018
  • Drug: Sarilumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 15, 2024): 612
• Original Estimated Enrollment (submitted: October 9, 2020): 290
• Estimated Study Completion Date: April 27, 2027
• Estimated Primary Completion Date: April 27, 2027 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Trials Administrator; 844-734-6643; clinicaltrials@regeneron.com

• Listed Location Countries: Belgium, United States

Administrative Information

• NCT Number: NCT04590326
• Other Study ID Numbers: R5668-ONC-1938; 2022-501904-83-00 ( Other Identifier: EUCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
• Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• URL: https://vivli.org/

• Current Responsible Party: Regeneron Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Regeneron Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

• PRS Account: Regeneron Pharmaceuticals
• Verification Date: March 2024