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

AstraZeneca823 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

823

Conditions

Squamous Cell Carcinoma of the Head and Neck

Interventions

MEDI4736BIOLOGICAL

Anti-PD-L1 antibody

TremelimumabBIOLOGICAL

Anti-CTLA-4 Antibody

MEDI4736+TremelimumabBIOLOGICAL

CetuximabBIOLOGICAL

Eligibility

Sex: ALLMin age: 18 YearsMax age: 130 Years

Medical Language ↔ Plain English

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

Locations (197)

Outcomes

Primary Outcomes

Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC)

Number of participants with Overall Survival (OS)

Time frame: From date of randomization until time of final analysis, an average of approximately 4 years

Overall Survival (OS) Median Duration in the PD-L1 TC/IC High Subgroup

Time from the date of randomization until death due to any cause (i.e., date of death or censoring - date of randomization + 1)

Time frame: From date of randomization until time of final analysis, an average of approximately 4 years

Secondary Outcomes

Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab + Tremelimumab Versus Standard of Care (SOC)

Number of participants with Overall Survival (OS)

Time frame: From date of randomization until time of final analysis, an average of approximately 4 years

Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup

Percentage of patients alive

Time frame: 12, 18 and 24 months after randomization

Progression Free Survival (PFS) in the PD-L1 TC/IC High Subgroup

Time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression). Progression is defined using Response Evaluation Criteria in Solid Tumours criteria (RECIST v1.1), as ≥20% increase in the sum of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Time frame: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years

Data from ClinicalTrials.gov

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5-fluorouracil (5FU)DRUG

Chemotherapy Agent

CisplatinDRUG

Chemotherapy agent

CarboplatinDRUG

Chemotherapy Agent

Research Site

Aurora, Colorado, United States

Research Site

Washington D.C., District of Columbia, United States

Research Site

Fort Myers, Florida, United States

Research Site

St. Petersburg, Florida, United States

Research Site

Tampa, Florida, United States

Research Site

Atlanta, Georgia, United States

Research Site

Chicago, Illinois, United States

Research Site

Baltimore, Maryland, United States

Research Site

Baltimore, Maryland, United States

Research Site

Boston, Massachusetts, United States

...and 187 more locations

Objective Response Rate (ORR) in the PD-L1 TC/IC High Subgroup

Number (%) of patients with at least 1 visit response of complete response (CR) or partial response (PR). Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) for target lesions (TL) and assessed by MRI or CT: CR: Disappearance of all TLs since baseline; PR: \>= 30% decrease in the sum of diameters of TLs; Overall Response (OR = CR + PR)

Time frame: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years

Duration of Response (DoR) in the PD-L1 TC/IC High Subgroup

Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression

Time frame: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years

Overall Survival (OS) Status in the All-comers (Full Analysis Set)

Number of participants with Overall Survival (OS)

Time frame: From date of randomization until time of final analysis, an average of approximately 4 years

Overall Survival (OS) Median Duration in the All-comers (Full Analysis Set)

Time from the date of randomization until death due to any cause (i.e., date of death or censoring - date of randomization + 1)

Time frame: From date of randomization until time of final analysis, an average of approximately 4 years

Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set)

Percentage of patients alive

Time frame: 12, 18 and 24 months after randomization

Progression Free Survival (PFS) in the All-comers (Full Analysis Set)

Time frame: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years

Objective Response Rate (ORR) in the All-comers (Full Analysis Set)

Time frame: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years

Duration of Response (DoR) in the All-comers (Full Analysis Set)

Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression

Time frame: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years