Study of REGN6569 and Cemiplimab in Adult Patients With Advanced Solid Tumor Malignancies

• ClinicalTrials.gov Identifier: NCT04465487
• Recruitment Status: Recruiting
• First Posted: July 10, 2020
• Last Update Posted: January 23, 2024
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Study Description

Brief Summary:

There are two main goals of this study: The first is to find the highest safe dose of REGN6569 when given with cemiplimab. The second is to get some initial information about how well the REGN6569 in combination with cemiplimab may help shrink certain types of cancer.

The study is also looking at:

• Side effects that may be experienced by people taking REGN6569 alone and with cemiplimab
• How REGN6569 and cemiplimab work in the body
• How much REGN6569 and cemiplimab is in your blood
• To see if REGN6569 can lower the number of Treg cells in tumors
• To see if REGN6569 and cemiplimab can shrink tumors when given together

Condition or disease	Intervention/treatment	Phase
Squamous Cell Carcinoma of Head and Neck	Drug: REGN6569; Drug: Cemiplimab	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 85 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study of REGN6569, an Anti-GITR mAb, With Cemiplimab in Patients With Advanced Solid Tumor Malignancies
• Actual Study Start Date: October 5, 2020
• Estimated Primary Completion Date: April 1, 2025
• Estimated Study Completion Date: June 22, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dose Escalation; REGN6569 lead-in, then combo therapy	Drug: REGN6569; Administered by intravenous (IV) infusion; Drug: Cemiplimab; Administered by IV infusion; Other Names: REGN2810; Libtayo
Experimental: Dose Expansion; Randomized 1:1 between cohorts Cohort 1: Concurrent start of REGN6569 + cemiplimab Cohort 2: REGN6569 lead-in, then combo therapy	Drug: REGN6569; Administered by intravenous (IV) infusion; Drug: Cemiplimab; Administered by IV infusion; Other Names: REGN2810; Libtayo

Outcome Measures

Primary Outcome Measures :

1. Incidence of dose-limited toxicities (DLTs) [ Time Frame: Up to 42 days ]
   Dose escalation period
2. Incidence and severity of treatment emergent adverse events(TEAEs) [ Time Frame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months ]
   Dose escalation period
3. Incidence and severity of adverse events of special interest (AESIs) [ Time Frame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months ]
   Dose escalation period
4. Incidence and severity of serious adverse events (SAEs) [ Time Frame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months ]
   Dose escalation period
5. Incidence and severity of grade ≥3 laboratory abnormalities [ Time Frame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months ]
   Dose escalation period
6. Objective response rate (ORR) [ Time Frame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months ]
   Dose expansion period
7. Characterize percentage change in intratumoral glucocorticoid-induced tumor necrosis factor receptor-Related (GITR)+ Treg density [ Time Frame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months ]
   Dose expansion period

Secondary Outcome Measures :

1. ORR [ Time Frame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months ]
   Dose escalation period
2. Disease control rate (DCR) [ Time Frame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months ]
   Dose escalation and expansion periods
3. Duration of Response (DOR) [ Time Frame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months ]
   Dose escalation and expansion periods
4. Progression-free Survival (PFS) [ Time Frame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months ]
   Dose escalation and expansion periods
5. Overall survival (OS) [ Time Frame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months ]
   Dose escalation and expansion periods
6. Drug concentrations of REGN6569 in serum [ Time Frame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months ]
   Dose escalation and expansion periods
7. Drug concentrations of cemiplimab in serum [ Time Frame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months ]
   Dose escalation and expansion periods
8. Immunogenicity as measured by anti-drug antibodies (ADA) to REGN6569 [ Time Frame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months ]
   Dose escalation and expansion periods
9. Immunogenicity as measured by anti-drug antibodies (ADA) to cemiplimab [ Time Frame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months ]
   Dose escalation and expansion periods

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

1. Dose escalation cohorts: Advanced stage (unresectable or metastatic) solid tumor malignancy, confirmed histologically or cytologically as defined in the protocol
2. Dose expansion cohorts: Advanced stage (unresectable or metastatic) head and neck squamous cell carcinoma (HNSCC), confirmed histologically or cytologically. Patients must have evidence of progression on anti-Programmed death-1 (receptor)/Programmed death ligand 1 (PD-1/PD-L1) blockade either as monotherapy or in combination with other therapies, as defined in the protocol
3. Mandatory biopsies: Able and willing to provide tumor tissue at baseline and while on treatment, with at least 1 soft tissue lesion amenable to biopsy by ultrasound or computed tomography (CT)-guided biopsy or under direct visualization as defined in the protocol

Key Exclusion Criteria:

1. Has previously received GITR-targeted therapy
2. Has received any previous systemic biologic therapy within 5 half-lives of first dose of study therapy as defined in the protocol
3. Has any condition that requires ongoing/continuous corticosteroid therapy (>10 mg prednisone/day or anti-inflammatory equivalent) within 14 days prior to the first dose of study therapy
4. Has ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments as defined in the protocol
5. Has a known history of, or any evidence of, interstitial lung disease, or active, non-infectious pneumonitis in the past 5 years. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis resolved ≥6 months prior to first dose of study therapy
6. Has uncontrolled infection with human immunodeficiency virus, hepatitis B or hepatitis C infection, or diagnosis of immunodeficiency
7. Has received a live vaccine within 4 weeks of planned start of study medication. For dose escalation only: Has received a COVID-19 vaccination within 1 week of planned start of study medication or for which the planned COVID-19 vaccinations would not be completed 1 week prior to start of study.
8. Has had prior allogeneic stem cell transplantation or received organ transplants at any time, or autologous stem cell transplantation
9. Has a history of malignancy within 2 years of date of first planned dose on study as defined in the protocol

Note: Other protocol-defined Inclusion/ Exclusion criteria apply

Contacts and Locations

Contacts

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

Locations

United States, California

Angeles Clinic and Research Institute - Clinic/Outpatient Facility; Active, not recruiting

Los Angeles, California, United States, 90025

United States, Florida

H.Lee Moffitt Cancer Center and Research Institute; Active, not recruiting

Tampa, Florida, United States, 33612

United States, Michigan

University of Michigan; Recruiting

Ann Arbor, Michigan, United States, 48109

START South Texas Accelerated Research Therapeutics; Active, not recruiting

Grand Rapids, Michigan, United States, 49503

Spain

Hospital Universitario Vall d'Hebrón; Recruiting

Barcelona, Spain, 08035

ICO l'Hospitalet - Hospital Duran i Reynals; Recruiting

Barcelona, Spain, 08908

MD Anderson Cancer Center; Recruiting

Madrid, Spain, 28033

Hospital Universitario Ramon y Cajal; Recruiting

Madrid, Spain, 28034

Hospital Universitario Fundacion Jimenez; Recruiting

Madrid, Spain, 28040

Hospital Universitario HM Sanchinarro; Recruiting

Madrid, Spain, 28050

Sponsors and Collaborators

Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

More Information

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04465487
• Other Study ID Numbers: R6569-ONC-1933; 2020-000075-20 ( EudraCT Number )
• First Posted: July 10, 2020
• Last Update Posted: January 23, 2024
• Last Verified: December 2023

Individual Participant Data (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; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
• Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data 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 the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
• URL: https://vivli.org/

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

Keywords provided by Regeneron Pharmaceuticals:

Unselected solid tumors dose escalation; HNSCC dose expansion; Advanced stage solid tumor malignancy; Unresectable; Metastatic

Additional relevant MeSH terms:

Neoplasms; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms by Site; Cemiplimab; Antineoplastic Agents, Immunological; Antineoplastic Agents