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

Phase 3

Completed

• Conditions: Squamous Cell Carcinoma of the Head and Neck
• Interventions: Biological: Cetuximab; Biological: MEDI4736; Biological: Tremelimumab; Biological: MEDI4736+Tremelimumab; Drug: 5-fluorouracil (5FU); Drug: Cisplatin; Drug: Carboplatin

• Registration Number: NCT02551159
• Lead Sponsor: AstraZeneca

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2015-09-09
• Study First Submitted QC: 2015-09-15
• Study First Posted: 2015-09-16
• Study Start: 2015-10-15
• Primary Completion: 2020-07-06
• Study Completion: 2021-05-21
• Results First Submitted: 2021-07-05
• Status Verified: 2021-09
• Results First Submitted QC: 2021-09-16
• Last Update Submitted: 2021-09-16
• Results First Posted: 2021-10-13
• Last Update Posted: 2021-10-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 823

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,

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of Care	Cetuximab	Standard of Care treatment
Monotherapy	MEDI4736	MEDI4736 monotherapy.
Combination Therapy	MEDI4736+Tremelimumab	MEDI4736+Tremelimumab combination therapy
Combination Therapy	Tremelimumab	MEDI4736+Tremelimumab combination therapy
Standard of Care	5-fluorouracil (5FU)	Standard of Care treatment
Standard of Care	Carboplatin	Standard of Care treatment
Standard of Care	Cisplatin	Standard of Care treatment

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC)	From date of randomization until time of final analysis, an average of approximately 4 years	Number of participants with Overall Survival (OS)
Overall Survival (OS) Median Duration in the PD-L1 TC/IC High Subgroup	From date of randomization until time of final analysis, an average of approximately 4 years	Time from the date of randomization until death due to any cause (i.e., date of death or censoring - date of randomization + 1)

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab + Tremelimumab Versus Standard of Care (SOC)	From date of randomization until time of final analysis, an average of approximately 4 years	Number of participants with Overall Survival (OS)
Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup	12, 18 and 24 months after randomization	Percentage of patients alive
Overall Survival (OS) Median Duration in the All-comers (Full Analysis Set)	From date of randomization until time of final analysis, an average of approximately 4 years	Time from the date of randomization until death due to any cause (i.e., date of death or censoring - date of randomization + 1)
Progression Free Survival (PFS) in the All-comers (Full Analysis Set)	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	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
Overall Survival (OS) Status in the All-comers (Full Analysis Set)	From date of randomization until time of final analysis, an average of approximately 4 years	Number of participants with Overall Survival (OS)
Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set)	12, 18 and 24 months after randomization	Percentage of patients alive
Objective Response Rate (ORR) in the All-comers (Full Analysis Set)	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	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)
Duration of Response (DoR) in the PD-L1 TC/IC High Subgroup	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	Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression
Progression Free Survival (PFS) in the PD-L1 TC/IC High Subgroup	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	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
Objective Response Rate (ORR) in the PD-L1 TC/IC High Subgroup	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	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)
Duration of Response (DoR) in the All-comers (Full Analysis Set)	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	Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression

Trial Locations

Locations (1)

Research Site; 🇻🇳 Ho Chi Minh city, Vietnam