Clinical trial NCT04465487: Study of REGN6569 and Cemiplimab in Adult Patients With Advanced Solid Tumor Malignancies
Official title: A Phase 1 Study of REGN6569, an Anti-GITR mAb, With Cemiplimab in Patients With Advanced Solid Tumor Malignancies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Squamous Cell Carcinoma of Head and Neck
Keywords: Unselected solid tumors dose escalation
HNSCC dose expansion
Advanced stage solid tumor malignancy
Unresectable
Metastatic
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-07-10
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: Incidence of dose-limited toxicities (DLTs)
timeFrame: Up to 42 days
measure: Incidence and severity of treatment emergent adverse events(TEAEs)
timeFrame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months
measure: Incidence and severity of adverse events of special interest (AESIs)
timeFrame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months
measure: Incidence and severity of serious adverse events (SAEs)
timeFrame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months
measure: Incidence and severity of grade ≥3 laboratory abnormalities
timeFrame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months
measure: Objective response rate (ORR)
timeFrame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months
measure: Characterize percentage change in intratumoral glucocorticoid-induced tumor necrosis factor receptor-Related (GITR)+ Treg density
timeFrame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months
Secondary outcomes:
measure: ORR
timeFrame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months
measure: Disease control rate (DCR)
timeFrame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months
measure: Duration of Response (DOR)
timeFrame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months
measure: Progression-free Survival (PFS)
timeFrame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months
measure: Overall survival (OS)
timeFrame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months
measure: Drug concentrations of REGN6569 in serum
timeFrame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months
measure: Drug concentrations of cemiplimab in serum
timeFrame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months
measure: Immunogenicity as measured by anti-drug antibodies (ADA) to REGN6569
timeFrame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months
measure: Immunogenicity as measured by anti-drug antibodies (ADA) to cemiplimab
timeFrame: Up to 90 days after the last dose of REGN6569 and/or cemiplimab, whichever is administered last, an average of approximately 30 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Angeles Clinic and Research Institute - Clinic/Outpatient Facility
state: California
city: Tampa
country: United States
facility: H.Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Grand Rapids
country: United States
facility: START South Texas Accelerated Research Therapeutics
state: Michigan
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebrón
city: Barcelona
country: Spain
facility: ICO l'Hospitalet - Hospital Duran i Reynals
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: