Study of REGN5668 Administered in Combination With Cemiplimab or REGN4018 in Adult Women With Recurrent Ovarian Cancer.

• ClinicalTrials.gov Identifier: NCT04590326
• Recruitment Status: Recruiting
• First Posted: October 19, 2020
• Last Update Posted: January 22, 2021
• 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: January 22, 2021
• Actual Study Start Date: December 9, 2020
• Estimated Primary Completion Date: February 26, 2026 (Final data collection date for primary outcome measure)

Current 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

• Original Primary Outcome Measures: Same as current

Current 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of REGN5668 Administered in Combination With Cemiplimab or REGN4018 in Adult Women With Recurrent Ovarian Cancer.
• Official Title: Phase 1/2 Study of REGN5668 (MUC16xCD28, a Costimulatory Bispecific) Administered in Combination With Cemiplimab or REGN4018 (MUC16xCD3)

Brief Summary

The primary objectives of the study are:

In the Dose Escalation Phase:

• To assess the safety, tolerability, and pharmacokinetics (PK) of REGN5668 alone and in separate combinations with cemiplimab or REGN4018, in order to determine a maximally tolerated dose(s) (MTD) or recommended phase 2 dose(s) (RP2D) of these combinations

In the Dose Expansion Phase:

• To assess the preliminary efficacy of REGN5668 in combination with cemiplimab or REGN4018, (separately by cohort and combination) as determined by the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

The secondary objectives of the study are:

In the Dose Escalation Phase:

• To assess the preliminary efficacy of REGN5668 in combination with cemiplimab or REGN4018 (separately by cohort and combination) as determined by ORR by RECIST 1.1

In the Dose Expansion Phase:

• To characterize the safety profile in each expansion cohort
• To characterize the PK of REGN5668 in combination with cemiplimab or REGN4018 (separately by cohort and combination)

In both the Dose Escalation and Dose Expansion Phases:

• To assess preliminary efficacy of REGN5668 in combination with cemiplimab or REGN4018 (separately by cohort and combination) as measured by ORR based on immune based therapy RECIST (iRECIST), best overall response (BOR), duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS) based on RECIST 1.1 and iRECIST
• To assess changes in CA-125 levels from baseline after treatment with REGN5668 in combinations with cemiplimab or REGN4018 (separately by cohort and combination)
• Immunogenicity of REGN5668, alone and in combinations with cemiplimab or 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

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-week monotherapy lead-in of REGN4018 will be administered by once weekly IV infusion. After lead-in, REGN5668 and REGN4018 will be administered concomitantly.

Study Arms

• Experimental: Module 1
  REGN5668 and cemiplimab
  Interventions:

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

  • Drug: REGN5668
  • Drug: REGN4018

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 9, 2020): 290
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 26, 2026
• Estimated Primary Completion Date: February 26, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

1. 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. In dose escalation, patients will provide either newly obtained biopsy (newly obtained biopsies at screening are required unless medically inappropriate and discussed with medical monitor) or archived tumor tissue. In expansion, patients will provide a fresh tumor biopsy in screening and on treatment. Hence, in expansion cohorts, only patients who (in the opinion of the investigator) have accessible lesions that can be biopsied without significant risk to the patient are eligible.
3. Expansion cohorts only: Has at least 1 lesion that is measurable by RECIST 1.1. Tumor lesions in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions after radiation.
4. Has a serum CA-125 level ≥2x ULN (in screening)
5. Has adequate organ and bone marrow function as defined in the protocol
6. Has a life expectancy of at least 3 months

Key Exclusion Criteria:

1. Has participated in a study of an investigational agent (except biologics and/or immunotherapy) or an investigational device within 4 weeks of first dose of study drug
2. Has received treatment with an approved systemic therapy (except biologics and/or immunotherapy) within 3 weeks or has not yet recovered as defined in the protocol
3. Prior anti-cancer immunotherapy as defined in the protocol
4. Has received radiation therapy or major surgery within 14 days of first administration of study drug as defined in the protocol
5. 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
6. Expansion cohorts only: Prior treatment with a MUC16-targeted therapy
7. Expansion cohorts only: More than 3 prior lines of cytotoxic chemotherapy for platinum-experienced and/or intolerant disease
8. 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
9. Has ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments as defined in the protocol
10. Has untreated or active primary brain tumor, CNS metastases, leptomeningeal disease, or spinal cord compression as defined in the protocol
11. Has encephalitis, meningitis, organic brain disease (eg, Parkinson's disease) or uncontrolled seizures in the year prior to first dose of study drug
12. Has history of clinically significant cardiovascular disease as defined in the protocol

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: United States

Administrative Information

• NCT Number: NCT04590326
• Other Study ID Numbers: R5668-ONC-1938; 2020-000063-23 ( EudraCT 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/

• Responsible Party: Regeneron Pharmaceuticals
• Study Sponsor: Regeneron Pharmaceuticals
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

• PRS Account: Regeneron Pharmaceuticals
• Verification Date: January 2021