Squamous Cell Carcinoma of Head and Neck
Conditions
Keywords
Unselected solid tumors dose escalation, HNSCC dose expansion, Advanced stage solid tumor malignancy, Unresectable, Metastatic
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
Interventions
DRUGREGN6569
Administered by intravenous (IV) infusion
DRUGCemiplimab
Administered by IV infusion
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
Countries
Spain, United States
Outcome results
None listed