A Study of Pembrolizumab (MK-3475) Plus Carboplatin and Paclitaxel as First-line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (MK-3475-B10/KEYNOTE B10)

Study Overview
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Brief Summary
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The goal of this study is to evaluate the efficacy and safety of pembrolizumab combined with carboplatin and paclitaxel as first line treatment in participants with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). No statistical hypothesis will be tested in this study.

Official Title
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A Phase 4, Single-arm, Open-label Clinical Study of Pembrolizumab (MK-3475) to Evaluate the Efficacy and Safety of MK-3475 Plus Carboplatin and Paclitaxel as First-line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE B10).

Conditions
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Squamous Cell Carcinoma of Head and Neck

Intervention / Treatment
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* Drug: Pembrolizumab
* Drug: Carboplatin
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has histologically or cytologically-confirmed diagnosis of R/M HNSCC that is considered incurable by local therapies Male participants refrain from donating sperm plus are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 95 days after carboplatin/paclitaxel Female participants are not pregnant or breastfeeding and are either not a woman of child-bearing potential (WOCBP) or use a contraceptive method that is highly effective or are abstinent from heterosexual intercourse during the intervention period and for at least 120 days after pembrolizumab or 30 days after paclitaxel or 6 months after carboplatin whichever occurs last, and agree not to donate or freeze eggs during this period Has adequate organ function Exclusion Criteria: Has disease that is suitable for local therapy administered with curative intent Has a life expectancy of less than 3 months and/or has rapidly progressive disease Has a diagnosed and/or treated additional malignancy within 5 years prior to allocation with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, curatively resected in situ cervical cancer and curatively resected in situ breast cancer Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis Has a history of or current non-infectious pneumonitis/interstitial lung disease that requires steroids Has an active infection requiring systemic therapy Has a known history of human immunodeficiency virus (HIV) infection Has a known history of Hepatitis B or Hepatitis C virus infection Has had an allogenic tissue/solid organ transplant

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pembrolizumab + Carboplatin + Paclitaxel<br>Participants will receive pembrolizumab plus carboplatin plus paclitaxel. Pembrolizumab will be administered via intravenous (IV) infusion at a dose of 200 mg on Day 1 of each 21-day cycle for up to 35 cycles (up to  2 years). Carboplatin will be administered via IV infusion at area under curve (AUC) 5 mg/mL/minute on Day 1 of each 21-day cycle for up to 6 cycles (up to  4 months). At investigator's choice, paclitaxel will be administered via IV infusion at a dose of 100 mg/m^2 on Day 1 and Day 8 of each 21-day cycle for up to 6 cycles (up to  4 months) or at a dose of 175 mg/m^2 on Day 1 of each 21-day cycle for up to 6 cycles (up to  4 months). | Drug: Pembrolizumab<br>* Pembrolizumab 200 mg IV infusion given on Day 1 of each 21-day cycle<br>* Other names: KEYTRUDA®;Drug: Carboplatin<br>* Carboplatin AUC 5 mg/mL/minute IV infusion given on Day 1 of each 21-day cycle<br>* Other names: PARAPLATIN®;Drug: Paclitaxel<br>* At investigator's choice, paclitaxel 100 mg/m^2 IV infusion given on Day 1 and Day 8 of each 21-day cycle or paclitaxel 175 mg/m^2 IV infusion given on Day 1 of each 21-day cycle<br>* Other names: ONXAL®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) per Response Evaluation Criteria in Solid Tumors Update and Clarification 1.1 (RECIST 1.1) which has been adjusted for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experience a CR or PR as assessed by blinded independent central review based on RECIST 1.1 will be presented. | Up to  20 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) | For participants who demonstrate a confirmed Complete Response (CR: Disappearance of all target lesions) or confirmed Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. RECIST 1.1 has been adjusted for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The DOR as assessed by blinded independent central review based on RECIST 1.1 will be presented. | Up to  47 months | 
| Progression-free Survival (PFS) | PFS is defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 has been adjusted for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. PFS as assessed by blinded independent central review based on RECIST 1.1 will be presented. | Up to  47 months | 
| Overall Survival (OS) | OS is defined as the time from first dose of study treatment to death due to any cause. | Up to  47 months | 
| Percentage of Participants who Experience an Adverse Event (AE) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience an AE will be reported. | Up to  27 months | 
| Percentage of Participants who Discontinue Study Treatment due to an AE | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study treatment due to an AE will be reported. | Up to  24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)