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
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- MedImmune LLC
- Enrollment
- 71
- Locations
- 1
- Primary Endpoint
- Number of subjects experiencing dose-limiting toxicities
Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 99 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Outcomes
Primary Outcomes
Number of subjects experiencing dose-limiting toxicities
Time Frame: First dose of study medications through 4 weeks after the first dose of study medication
Change from Baseline in laboratory evaluations
Time Frame: Screening through 3 months after the last dose of study medication
Number of subjects reporting serious adverse events
Time Frame: Screening through 3 months after the last dose of study medication
Change from Baseline in electrocardiograms
Time Frame: Screening through 3 months through last dose of study medication
Number of subjects reporting adverse events
Time Frame: Screening through 3 months after the last dose of study medication
Change from Baseline in vital signs
Time Frame: Screening through 3 months after the last dose of study medication
Secondary Outcomes
- 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)
- Duration of Response(Screening through 5 years after the last subject receives the first 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)
- 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)
- 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)
- 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)