A Phase I Study to Evaluate the Safety, Tolerability and Efficacy of MEDI4736 (Durvalumab) With Tremelimumab in Head and Neck Cancer

Study Overview
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Brief Summary
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This is a multicenter, open-label, dose-exploration and dose-expansion study to evaluate the safety, tolerability, antitumor activity, PK, pharmacodynamics, and immunogenicity of MEDI4736 in combination with tremelimumab in subjects with recurrent/metastatic squamous cell carcinoma of the head and neck.

Official Title
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A Phase I Study to Evaluate the Safety, Tolerability, and Efficacy of MEDI4736 in Combination With Tremelimumab in Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Conditions
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Squamous Cell Carcinoma of the Head and Neck

Intervention / Treatment
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* Biological: MEDI4736
* Biological: tremelimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects 18 years and older Histologically or cytologically confirmed recurrent or metastatic squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx or larynx) that is incurable by local therapy. Subjects who are treatment-naive or pretreated (prior anti-PD-1 or anti-PD-L1 required) in the recurrent/metastatic setting. Subject eligibility will be based on PD-L1 expression as determined by a specified IHC assay. Exclusion Criteria: Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment, receipt of last dose of an approved anticancer therapy within 21 days Concurrent or prior use of immunosuppressive medication within 14 days Active or prior documented autoimmune or inflammatory disease within 3 years with some exceptions.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDI4736 + tremelimumab<br> | Biological: MEDI4736<br>* MEDI4736 will be administered by IV infusion in combination with tremelimumab.<br>Biological: tremelimumab<br>* Tremelimumab will be administered by IV infusion in combination with MEDI4736.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects reporting adverse events |  | Screening through 3 months after the last dose of study medication | 
| Number of subjects reporting serious adverse events |  | Screening through 3 months after the last dose of study medication | 
| Number of subjects experiencing dose-limiting toxicities |  | First dose of study medications through 4 weeks after the first dose of study medication | 
| Change from Baseline in laboratory evaluations |  | Screening through 3 months after the last dose of study medication | 
| Change from Baseline in electrocardiograms |  | Screening through 3 months through last dose of study medication | 
| Change from Baseline in vital signs |  | Screening through 3 months after the last dose of study medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate |  | Screening through 5 years after the last subject receives the first dose of study medication | 
| Individual MEDI4736 concentrations |  | First dose of MEDI4736 through 3 months after the last dose of study medication | 
| Number of subjects that develop changes in detectable antidrug antibodies to MEDI4736 |  | First dose of MEDI4736 through 6 months after the last dose of study medication | 
| Disease Control Rate |  | Screening through 5 years after the last subject receives the first dose of study medication | 
| Duration of Response |  | Screening through 5 years after the last subject receives the first dose of study medication | 
| Progression Free Survival |  | Screening through 5 years after the last subject receives the first dose of study medication | 
| Overall Survival |  | Screening through 5 years after the last subject receives the first dose of study medication | 
| Individual tremelimumab concentrations |  | First dose of tremelimumab through 3 months after the last dose of study medication | 
| MEDI4736 area under the concentration-curve |  | First dose of MEDI4736 through 3 months after the last dose of study medication | 
| Tremelimumab area under the concentration-curve |  | First dose of tremelimumb through 3 months after the last dose of study medication | 
| Number of subjects that develop changes in detectable antidrug antibodies to tremelimumab |  | First dose of tremelimumab through 6 months after the last dose of study medication |