A Phase 1 Study of MEDI4736 in Combination With Tremelimumab in Subjects With Advanced Solid Tumors

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 and immunogenicity of MEDI4736 in combination with tremelimumab in subjects with select advanced solid tumors.

Official Title
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A Phase I Study of MEDI4736 (Anti-PD-L1 Antibody) in Combination With Tremelimumab (Anti-CTLA-4 Antibody) in Subjects With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

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 Histologic confirmation of advanced solid tumors Subjects must have recurrent/metastatic disease and may have been previously treated in the recurrent/metastatic setting. Exclusion Criteria: Any concurrent chemotherapy, immune-mediated therapy or biologic or hormonal therapy for cancer treatment Active or prior documented autoimmune disease within the past 2 years Current or prior use of immunosuppressive medication within 14 days 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>Subjects with multiple tumor types. | Biological: MEDI4736<br>* MEDI4736 is administered by IV infusion in combination with tremelimumab<br>Biological: tremelimumab<br>* Tremelimumab is 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 15 months after the last subject enters re-treatment | 
| Number of subjects reporting serious adverse events |  | Screening through 15 months after the last subject enters re-treatment | 
| Number of subjects experiencing a dose-limiting toxicity |  | First dose of study medication 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 vital signs |  | Screening through 3 months after the last dose of study medication | 
| Change from Baseline in electrocardiogram evaluations |  | Screening through 3 months after the last dose of study medication | 
| Overall Response Rate in Select Tumor Types |  | First dose of study medication through 15 months after the last subject enters re-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate |  | First dose of study medication through 15 months after the last subject enters re-treatment | 
| Disease Control Rate |  | First dose of study medication through 15 months after the last subject enters re-treatment | 
| Duration of Response |  | First dose of study medication through 15 months after the last subject enters re-treatment | 
| Progression-Free Survival |  | First dose of study medication through 15 months after the last subject enters re-treatment | 
| Overall Survival |  | First dose of study medication through 15 months after the last subject enters re-treatment | 
| Individual MEDI4736 concentrations |  | First dose of MEDI4736 through 3 months after the last 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 tremelimumab through 3 months after the last dose of study medication | 
| Number of subjects that develop detectable antidrug antibodies to MEDI4736 |  | First dose of MEDI4736 through 3 months after the last dose of study medication | 
| Number of subjects that develop antidrug antibodies to tremelimumab |  | First dose of tremelimumab through 3 months after the last dose of study medication | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced solid tumors, durvalumab, tremelimumab