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

Study Overview
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Brief Summary
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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

Official Title
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A Phase 1 Study of REGN6569, an Anti-GITR mAb, With Cemiplimab in Patients With Advanced Solid Tumor Malignancies

Conditions
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Squamous Cell Carcinoma of Head and Neck

Intervention / Treatment
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* Drug: REGN6569
* Drug: Cemiplimab


Participation Criteria
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Eligibility Criteria
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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. 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 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: 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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation<br>REGN6569 lead-in, then combo therapy | Drug: REGN6569<br>* Administered by intravenous (IV) infusion<br>Drug: Cemiplimab<br>* Administered by IV infusion<br>* Other names: Libtayo;|
| Experimental: Dose Expansion<br>Randomized 1:1 between cohorts Cohort 1: Concurrent start of REGN6569 + cemiplimab Cohort 2: REGN6569 lead-in, then combo therapy | Drug: REGN6569<br>* Administered by intravenous (IV) infusion<br>Drug: Cemiplimab<br>* Administered by IV infusion<br>* Other names: Libtayo;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Dose escalation period | Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months | 
| Disease control rate (DCR) | Dose escalation and expansion periods | Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months | 
| Duration of Response (DOR) | Dose escalation and expansion periods | Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months | 
| Progression-free Survival (PFS) | Dose escalation and expansion periods | Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months | 
| Overall survival (OS) | Dose escalation and expansion periods | Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months | 
| Drug concentrations of REGN6569 in serum | Dose escalation and expansion periods | Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months | 
| Drug concentrations of cemiplimab in serum | Dose escalation and expansion periods | Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months | 
| Immunogenicity as measured by anti-drug antibodies (ADA) to REGN6569 | Dose escalation and expansion periods | Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months | 
| Immunogenicity as measured by anti-drug antibodies (ADA) to cemiplimab | Dose escalation and expansion periods | Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Unselected solid tumors dose escalation, HNSCC dose expansion, Advanced stage solid tumor malignancy, Unresectable, Metastatic