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

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

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 Overview

• Status: Completed
• Conditions: Squamous Cell Carcinoma of the Head and Neck
• Intervention / Treatment: Biological: MEDI4736; Biological: tremelimumab

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • Research Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Research Site
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Research Site
  • California
    • La Jolla, California, United States, 92093
      • Research Site
    • Los Angeles, California, United States, 90025
      • Research Site
    • Los Angeles, California, United States, 90095
      • Research Site
    • San Francisco, California, United States, 94143
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Research Site
  • Florida
    • Orlando, Florida, United States, 32806
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Research Site
  • Kansas
    • Fairway, Kansas, United States, 66205
      • Research Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Research Site
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Research Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Research Site
  • New York
    • New York, New York, United States, 10016
      • Research Site
    • New York, New York, United States, 10065
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97213
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Research Site
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Research Site
  • Texas
    • San Antonio, Texas, United States, 78229
      • Research Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female subjects
2. 18 years and older
3. 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.
4. Subjects who are treatment-naive or pretreated (prior anti-PD-1 or anti-PD-L1 required) in the recurrent/metastatic setting.
5. Subject eligibility will be based on PD-L1 expression as determined by a specified IHC assay.

Exclusion Criteria:

1. Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment, receipt of last dose of an approved anticancer therapy within 21 days
2. Concurrent or prior use of immunosuppressive medication within 14 days
3. Active or prior documented autoimmune or inflammatory disease within 3 years with some exceptions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MEDI4736 + tremelimumab	Biological: MEDI4736; MEDI4736 will be administered by IV infusion in combination with tremelimumab.; Biological: tremelimumab; Tremelimumab will be administered by IV infusion in combination with MEDI4736.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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
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 electrocardiograms	Screening through 3 months through last dose of study medication

Secondary Outcome Measures

Outcome Measure	Time Frame
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
Objective Response 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 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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Biomarkers	Evaluate biomarkers that may correlate with clinical activity of MEDI4736 monotherapy and in combination with tremelimumab	Screening through 3 months after the last patient receives the first dose of study medication
Change from Baseline in Patient-Reported Outcomes		Screening through 5 years after the last patient receives the first dose of study medication

Collaborators and Investigators

• Sponsor: MedImmune LLC

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 15, 2014
• Primary Completion (ACTUAL): September 21, 2017
• Study Completion (ACTUAL): September 21, 2017

Study Registration Dates

• First Submitted: October 2, 2014
• First Submitted That Met QC Criteria: October 9, 2014
• First Posted (ESTIMATE): October 13, 2014

Study Record Updates

• Last Update Posted (ACTUAL): October 23, 2017
• Last Update Submitted That Met QC Criteria: October 20, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab; Tremelimumab
• Other Study ID Numbers: D4190C00011