Phase III Open Label Study of MEDI 4736 With/Without Tremelimumab Versus Standard of Care (SOC) in Recurrent/Metastatic Head and Neck Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 12 July 2021
• Main ID: NCT02551159
• Date of registration: 09/09/2015
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: Phase III Open Label Study of MEDI 4736 With/Without Tremelimumab Versus Standard of Care (SOC) in Recurrent/Metastatic Head and Neck Cancer KESTREL
• Scientific title: A Phase III Randomized, Open-label, Multi-center, Global Study of MEDI4736 Alone or in Combination With Tremelimumab Versus Standard of Care in the Treatment of First-line Recurrent or Metastatic Squamous Cell Head and Neck Cancer Patients
• Date of first enrolment: October 15, 2015
• Target sample size: 823
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02551159
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Austria, Belgium, Brazil, Bulgaria, Canada, France, Germany, Greece, India, Italy, Japan, Korea, Republic of, Philippines, Poland, Portugal, Romania, Russian Federation, Slovakia, Spain, Taiwan, Thailand, Ukraine, United Kingdom, United States, Vietnam

Contacts

• Name: Richard Olsson

• Name: Tanguy Seiwert
• Affiliation: The University of Chicago, 5841 S Maryland Ave, Chicago, IL 60637

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Age =18 years at the time of screening

2. Documented evidence of recurrent or metastatic SCCHN (oral cavity, oropharynx,
hypopharynx, or larynx).

3. A fresh tumor biopsy for the purpose of screening or an available archival tumor
sample. Tumor lesions used for fresh biopsies should not be the same lesions used as
RECIST target lesions, unless there are no other lesions suitable for biopsy.

4. No prior systemic chemotherapy for recurrent or metastatic disease

5. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance
status of 0 or 1 at enrollment

6. No prior exposure to immune-mediated therapy,

Exclusion Criteria:

1. Histologically or cytologically confirmed head and neck cancer of any other primary
anatomic location in the head and neck not specified in the inclusion criteria
including patients with SCCHN of unknown primary or non-squamous histologies (eg,
nasopharynx or salivary gland)

2. Tumor progression or recurrence within 6 months of last dose of platinum therapy in
the primary treatment setting

3. Receipt of any radiotherapy or hormonal therapy for cancer treatment within 30 days
prior to first dose of study treatment

4. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [eg, colitis, Crohn's disease], diverticulitis



Age minimum: 18 Years
Age maximum: 130 Years
Gender: All

Health Condition(s) or Problem(s) studied

Squamous Cell Carcinoma of the Head and Neck

Intervention(s)

Biological: Cetuximab

Drug: Carboplatin

Biological: MEDI4736

Biological: Tremelimumab

Biological: MEDI4736+Tremelimumab

Drug: 5-fluorouracil (5FU)

Drug: Cisplatin

Primary Outcome(s)

To assess the efficacy of MEDI4736 monotherapy compared to Standard of Care (SoC, EXTREME) in terms of overall survival (OS) [Time Frame: Estimated up to 2 years]

Secondary Outcome(s)

The efficacy of MEDI4736 + tremelimumab combination therapy compared to MEDI4736 monotherapy in terms of Overall Survival (OS) [Time Frame: Estimated up to 2 years]

The efficacy of MEDI4736 + tremelimumab combination therapy compared to MEDI4736 monotherapy in terms of Progression Free Survival (PFS) [Time Frame: Estimated up to 2 years]

The pharmacokinetics (PK) analysis of MEDI4736 and Tremelimumab using Area Under the Curve (AUC) [Time Frame: Estimated up to 6 months]

The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Duration of Response (DoR) [Time Frame: Estimated up to 2 years]

The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Time to Response (TTR) [Time Frame: Estimated up to 2 years]

The efficacy of MEDI4736 monotherapy vs SoC in terms of Best Objective Response (BoR) [Time Frame: Estimated up to 2 Years]

The efficacy of MEDI4736 monotherapy vs SoC in terms of Time to First Subsequent Therapy(TFST) [Time Frame: Estimated up to 2 years]

The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Second Progression (PFS2) [Time Frame: Estimated up to 2 years]

The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Time to Second Subsequent Therapy (TSST) [Time Frame: Estimated up to 2 years]

HRQoL in patients treated with MEDI4736 + tremelimumab or MEDI4736 compared to SoC using the European Organization for Research and Treatment of Cancer Head and Neck Quality of Life (EORTC QLQ-H&N35) module [Time Frame: Estimated up to 2 years]

The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Objective Response Rate (ORR) [Time Frame: Estimated up to 2 years]

The efficacy of MEDI4736 monotherapy compared to SoC in terms of Progression Free Survival (PFS) and Second Progression (PFS2) [Time Frame: Estimated up to 2 years]

The efficacy of MEDI4736 monotherapy vs SoC in terms of proportion of patients Alive and Progression Free at 6 and 12 Months (APF6, APF12) over a period of 1 year [Time Frame: Estimated up to 1 year]

The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Best Objective Response (BoR) [Time Frame: Estimated up to 2 years]

The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Overall Survival (OS) [Time Frame: Estimated up to 2 years]

The efficacy of MEDI4736 monotherapy vs SoC in terms of Time to Response (TTR) [Time Frame: Estimated up to 2 years]

The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Overall Survival at 12, 18 and 24 Months (OS12, OS18, OS24) over a period of 2 years [Time Frame: Estimated up to 2 Years]

The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Progression Free Survival (PFS) [Time Frame: Estimated up to 2 years]

HRQoL in patients treated with MEDI4736 + tremelimumab or MEDI4736 compared to SoC using the European Organization for Research and Treatment of Cancer Core Quality of Life (EORTC QLQ-C30) module [Time Frame: Estimated up to 2 years]

The efficacy of MEDI4736 monotherapy vs SoC in terms of Time to Second Subsequent Therapy(TSST) [Time Frame: Estimated up to 2 years]

The efficacy of MEDI4736 + tremelimumab combination therapy compared to MEDI4736 monotherapy in terms of Objective Response Rate (ORR) [Time Frame: Estimated up to 2 years]

The efficacy of MEDI4736 monotherapy compared to SoC in terms of Objective Response Rate (ORR) [Time Frame: Estimated up to 2 years]

The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Alive and Progression Free at 6 and 12 Months (APF6, APF12) over a period of 1 year [Time Frame: Estimated up to 1 Year]

The efficacy of MEDI4736 monotherapy compared to SoC in terms of Overall Survival (OS) and Overall Survival at 12, 18 and 24 months (OS12, OS18, OS24) [Time Frame: Estimated up to 2 Years]

The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Time to First Subsequent Therapy (TFST) [Time Frame: Estimated up to 2 years]

The efficacy of MEDI4736 monotherapy vs SoC in terms of Duration of Response(DoR) [Time Frame: Estimated up to 2 years]

The pharmacokinetics (PK) analysis of MEDI4736 and Tremelimumab using Maximum Plasma Concentration (Cmax) [Time Frame: Estimated up to 6 months]

The immunogenicity of MEDI4736 and tremelimumab [Time Frame: Estimated up to 2 years]

Secondary ID(s)

D419LC00001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors