Study of Nivolumab in Combination With Ipilimumab Compared to the Standard of Care (Extreme Regimen) as First Line Treatment in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Study Overview
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Brief Summary
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The main purpose of this study is to compare nivolumab and ipilimumab with the extreme regimen as first line treatment in patients with recurrent or metastatic squamous cell of the head and neck cancer

Official Title
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An Open Label, Randomized, Two Arm Phase III Study of Nivolumab in Combination With Ipilimumab Versus Extreme Study Regimen (Cetuximab + Cisplatin/Carboplatin + Fluorouracil) as First Line Therapy in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Biological: Nivolumab
* Biological: Ipilimumab
* Drug: Cetuximab/Erbitux
* Drug: Cisplatin/Platinol
* Drug: Carboplatin/Paraplatin
* Drug: Fluorouracil/Adrucil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed metastatic or recurrent squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx & larynx) that is not amenable to curative therapy. No prior systemic cancer therapy for recurrent or metastatic disease (except if chemotherapy was part of multimodal treatment completed 6 months prior to enrolment). Measurable disease detected by imaging exam (CT or MRI). Have tumor tissue for PD L1 expression testing, and for oropharyngeal cancer have results from testing of HPV p16 status. Exclusion Criteria: Metastatic or recurrent carcinoma of the nasopharynx, squamous cell carcinoma of unknown primary, squamous cell carcinoma originating from skin and salivary glands or non squamous histologies (eg. mucosal melanoma). No prior treatment with anti PD1, anti PD L1, anti CTLA 4 antibody or any other antibody or drugs targeting T cell costimulation or checkpoint pathways, or cetuximab or EGFR inhibitors in any treatment setting. Participants with certain diseases such as active autoimmune disease, type I diabetes, hypothyroidism that needs hormone replacement, active infection, psychiatric disorder. Inadequate hematologic, renal or hepatic function. Other protocol defined inclusion/exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nivolumab and Ipilimumab<br>Specified dose on specified days | Biological: Nivolumab<br> <br> * Other names: Opdivo;Biological: Ipilimumab<br> <br> * Other names: Yervoy;|
| Active Comparator: Extreme Regimen<br>Specified dose on specified days | Drug: Cetuximab/Erbitux<br> <br> Drug: Cisplatin/Platinol<br> <br> Drug: Carboplatin/Paraplatin<br> <br> Drug: Fluorouracil/Adrucil<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) in Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) ≥20 | Overall survival (OS) is defined as the time between randomization and death. For participants without documentation of death, OS will be censored on the last date the participant was known to be alive. Overall survival will be censored at the date of randomization for participants who were randomized but had no follow-up. Survival follow-up will be conducted every 3 months after participants off-treatment date. (Based on Kaplan-Meier estimates) | From randomization to date of death or date the participant was last known to be alive (Up to approximately 55 months) | 
| Overall Survival (OS) in All Randomized Participants | Overall survival (OS) is defined as the time between randomization and death. For participants without documentation of death, OS will be censored on the last date the participant was known to be alive. Overall survival will be censored at the date of randomization for participants who were randomized but had no follow-up. Survival follow-up will be conducted every 3 months after participants off-treatment date. (Based on Kaplan-Meier estimates) | From randomization to date of death or date the participant was last known to be alive (Up to approximately 55 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) in Randomized Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) ≥ 1 | Overall survival (OS) is defined as the time between randomization and death. For participants without documentation of death, OS will be censored on the last date the participant was known to be alive. Overall survival will be censored at the date of randomization for participants who were randomized but had no follow-up. Survival follow-up will be conducted every 3 months after participants off-treatment date. (Based on Kaplan-Meier estimates) | From randomization to date of death or date the participant was last known to be alive (Up to approximately 65 months) | 
| Progression Free Survival (PFS) | PFS is defined as the time between the date of randomization and the date of first documented tumor progression, based on Blinded Independent Central Review (BICR) assessments (per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria), or death due to any cause, whichever occurs first. Participants who neither progress nor die will be censored on the date of their last tumor assessment. Participants who receive subsequent anti-cancer therapy prior to documented progression, will be censored on the date of their last tumor assessment prior to subsequent therapy. (Based on Kaplan-Meier Estimates) Progression is defined as at least a 20% increase in the sum of diameters of target lesions, in addition the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). | From randomization to disease progression or death (Up to approximately 65 months) | 
| Objective Response Rate (ORR) | Objective Response Rate (ORR) is defined as the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria by blinded independent central review (BICR) assessment. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | From randomization up to approximately 65 months | 
| Duration of Objective Response (DOR) | The time between the first documented response (Complete response (CR) or partial response (PR)) and progression or death, per RECIST 1.1 by blinded independent central review (BICR) assessment. (Based on Kaplan-Meier Estimates) Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | From randomization to the first documented response (CR or PR) and progression (up to approximately 65 months) |