Study of REGN6569 and Cemiplimab in Adult Patients With Advanced Solid Tumor Malignancies
- Conditions
- Squamous Cell Carcinoma of Head and Neck
- Interventions
- Registration Number
- NCT04465487
- Lead Sponsor
- Regeneron Pharmaceuticals
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 38
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Expansion Cemiplimab Randomized 1:1 between cohorts Cohort 1: Concurrent start of REGN6569 + cemiplimab Cohort 2: REGN6569 lead-in, then combo therapy Dose Escalation REGN6569 REGN6569 lead-in, then combo therapy Dose Expansion REGN6569 Randomized 1:1 between cohorts Cohort 1: Concurrent start of REGN6569 + cemiplimab Cohort 2: REGN6569 lead-in, then combo therapy Dose Escalation Cemiplimab REGN6569 lead-in, then combo therapy
- Primary Outcome Measures
Name Time Method 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 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
Incidence of dose-limited toxicities (DLTs) Up to 42 days Dose escalation period
Characterize percentage change in intratumoral 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
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
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
- Secondary Outcome Measures
Name Time Method 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
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
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
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
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
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
Trial Locations
- Locations (10)
Angeles Clinic and Research Institute - Clinic/Outpatient Facility
🇺🇸Los Angeles, California, United States
H.Lee Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
START South Texas Accelerated Research Therapeutics
🇺🇸Grand Rapids, Michigan, United States
Hospital Universitario Vall d'Hebrón
🇪🇸Barcelona, Spain
ICO l'Hospitalet - Hospital Duran i Reynals
🇪🇸Barcelona, Spain
MD Anderson Cancer Center
🇪🇸Madrid, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jimenez
🇪🇸Madrid, Spain
Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Spain