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

AstraZeneca

Status and phase: Completed; Phase 3

Conditions: Squamous Cell Carcinoma of the Head and Neck

Treatments: Drug: Cisplatin; Biological: Cetuximab; Drug: 5-fluorouracil (5FU); Biological: Tremelimumab; Biological: MEDI4736; Biological: MEDI4736+Tremelimumab; Drug: Carboplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT02551159

D419LC00001

Details and patient eligibility

About

This is a randomized, open-label, multi-center, 3-arm, global Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination or MEDI4736 monotherapy versus SoC (EXTREME regimen) in the treatment of patients with SCCHN who have not received prior systemic chemotherapy for recurrent or metastatic disease.

Full description

Patients will be randomized in a 2:1:1 ratio to MEDI4736 + tremelimumab combination therapy, MEDI4736 monotherapy, or SoC. Patients in all arms will continue therapy until progression. Tumor assessments will be performed on computed tomography scans or magnetic resonance imaging scans, preferably with intravenous (IV) contrast. Efficacy for all patients will be assessed by objective tumor assessments every 6 weeks for the first 24 weeks, then every 8 weeks thereafter until treatment discontinuation due to progression or toxicity. All patients will be followed every 3 months for survival after progression is confirmed.

Enrollment: 823 patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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823 participants in 3 patient groups

Monotherapy

Experimental group

Description:

MEDI4736 monotherapy.

Treatment:

Biological: MEDI4736

Combination Therapy

Experimental group

Description:

MEDI4736+Tremelimumab combination therapy

Treatment:

Biological: MEDI4736+Tremelimumab

Biological: Tremelimumab

Standard of Care

Active Comparator group

Description:

Standard of Care treatment

Treatment:

Biological: Cetuximab

Drug: Carboplatin

Drug: 5-fluorouracil (5FU)

Drug: Cisplatin