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

Sponsor

Regeneron Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04465487

Collaborator

(none)

Enrollment

Locations

Arm

69.1

Anticipated Duration (Months)

8.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

For dose escalation cohorts, the primary objective is to evaluate the safety and tolerability of REGN6569 as monotherapy lead-in and in combination with cemiplimab.

For dose expansion cohorts, the co-primary objectives are:

To assess the preliminary efficacy of REGN6569 in combination with cemiplimab, as measured by objective response rate (ORR)
To assess the preliminary pharmacodynamic activity of REGN6569 as lead-in monotherapy, as measured by intratumoral Glucocorticoid-Induced Tumor necrosis factor receptor-Related (GITR)+ Treg depletion

Secondary Objectives are:

For dose escalation cohorts:

To assess preliminary efficacy of REGN6569 in combination with cemiplimab, as measured by ORR, disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS)
To characterize the pharmacokinetics (PK) of REGN6569 alone and in combination with cemiplimab
To assess the immunogenicity of REGN6569 and cemiplimab

For expansion cohorts:

To characterize the safety profile in each expansion cohort
To assess preliminary efficacy of REGN6569 in combination with cemiplimab, as measured by DCR, DOR, PFS, and OS
To characterize the PK of REGN6569 alone and in combination with cemiplimab
To assess the immunogenicity of REGN6569 and cemiplimab

Condition or Disease	Intervention/Treatment	Phase
Squamous Cell Carcinoma of Head and Neck	Drug: REGN6569 Drug: Cemiplimab	Phase 1

Study Design

Study Type:

Interventional

Anticipated 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 :

Oct 5, 2020

Anticipated Primary Completion Date :

Jul 8, 2026

Anticipated Study Completion Date :

Jul 8, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: REGN6569+cemiplimab REGN6569 lead-in	Drug: REGN6569 Administered by intravenous (IV) infusion Drug: Cemiplimab Administered by IV infusion Other Names: REGN2810 Libtayo

Arm

Intervention/Treatment

Experimental: REGN6569+cemiplimab

REGN6569 lead-in

Drug: REGN6569

Administered by intravenous (IV) infusion

Drug: Cemiplimab

Administered by IV infusion

Other Names:

REGN2810

Libtayo

Outcome Measures

Primary Outcome Measures

Incidence of dose-limited toxicities (DLTs) [Up to 42 days]
Dose escalation period
Incidence and severity of treatment emergent adverse events(TEAEs) [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
Incidence and severity of adverse events of special interest (AESIs) [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
Incidence and severity of serious adverse events (SAEs) [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
Incidence and severity of grade ≥3 laboratory abnormalities [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
Objective response rate (ORR) [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
Percentage change in glucocorticoid-induced tumor necrosis factor receptor-Related(GITR)+ Treg density [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

ORR [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
Disease control rate (DCR) [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
Duration of Response (DOR) [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
Progression-free Survival (PFS) [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
Overall survival (OS) [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
Drug concentrations of REGN6569 in serum [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
Drug concentrations of cemiplimab in serum [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
Immunogenicity as measured by anti-drug antibodies (ADA) to REGN6569 [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
Immunogenicity as measured by anti-drug antibodies (ADA) to cemiplimab [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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Dose escalation cohorts: Advanced stage (unresectable or metastatic) solid tumor malignancy, confirmed histologically or cytologically as defined in the protocol
Dose expansion cohorts: Advanced stage (unresectable or metastatic) head and neck squamous cell carcinoma(HNSCC), confirmed histologically or cytologically as defined in the protocol
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

All Cohorts:

Has no prior history of immune checkpoint blockade (ICB) therapy
Has exhausted all approved available treatment options for their disease, with no other standard therapy likely to convey clinical benefit as defined in the protocol

Key Exclusion Criteria:

Has previously received GITR-targeted therapy
Has received any previous systemic biologic therapy within 5 half-lives of first dose of study therapy as defined in the protocol
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
Has ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments as defined in the protocol
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
Has uncontrolled infection with human immunodeficiency virus, hepatitis B or hepatitis C infection, or diagnosis of immunodeficiency
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.
Has had prior allogeneic stem cell transplantation or received organ transplants at any time, or autologous stem cell transplantation

Note: Other protocol-defined Inclusion/ Exclusion criteria apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Angeles Clinic and Research Institute - Clinic/Outpatient Facility	Los Angeles	California	United States	90025
2	H.Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
3	University of Michigan	Ann Arbor	Michigan	United States	48109
4	START South Texas Accelerated Research Therapeutics	Grand Rapids	Michigan	United States	49503
5	Hospital Universitario Vall d'Hebrón	Barcelona		Spain	08035
6	ICO l'Hospitalet - Hospital Duran i Reynals	Barcelona		Spain	08908
7	MD Anderson Cancer Center	Madrid		Spain	28033
8	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
9	Hospital Universitario Fundacion Jimenez	Madrid		Spain	28040
10	Hospital Universitario HM Sanchinarro	Madrid		Spain	28050