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)

• ClinicalTrials.gov Identifier: NCT04489888
• Recruitment Status: Active, not recruiting
• First Posted: July 28, 2020
• Last Update Posted: March 29, 2023
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: July 27, 2020
• First Posted Date: July 28, 2020
• Last Update Posted Date: March 29, 2023
• Actual Study Start Date: October 27, 2020
• Actual Primary Completion Date: February 20, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 27, 2020)

Objective Response Rate (ORR) [ Time Frame: Up to ~20 months ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 27, 2020)

• Duration of Response (DOR) [ Time Frame: Up to ~47 months ]
  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.
• Progression-free Survival (PFS) [ Time Frame: Up to ~47 months ]
  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.
• Overall Survival (OS) [ Time Frame: Up to ~47 months ]
  OS is defined as the time from first dose of study treatment to death due to any cause.
• Percentage of Participants who Experience an Adverse Event (AE) [ Time Frame: Up to ~27 months ]
  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.
• Percentage of Participants who Discontinue Study Treatment due to an AE [ Time Frame: Up to ~24 months ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• Official Title: 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).
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Squamous Cell Carcinoma of Head and Neck

Intervention

• Drug: Pembrolizumab
  Pembrolizumab 200 mg IV infusion given on Day 1 of each 21-day cycle
  Other Names:

  • MK-3475
  • KEYTRUDA®
• Drug: Carboplatin
  Carboplatin AUC 5 mg/mL/minute IV infusion given on Day 1 of each 21-day cycle
  Other Name: PARAPLATIN®
• Drug: Paclitaxel
  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
  Other Names:

  • TAXOL®
  • ONXAL®

Study Arms

Experimental: Pembrolizumab + Carboplatin + Paclitaxel

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).

Interventions:

• Drug: Pembrolizumab
• Drug: Carboplatin
• Drug: Paclitaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 27, 2023): 101
• Original Estimated Enrollment (submitted: July 27, 2020): 100
• Estimated Study Completion Date: July 25, 2024
• Actual Primary Completion Date: February 20, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Brazil, Canada, United States

Administrative Information

• NCT Number: NCT04489888
• Other Study ID Numbers: 3475-B10; MK-3475-B10 ( Other Identifier: Merck )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: March 2023