A Study of MK-3475A (Pembrolizumab Formulated With MK-5180) in Japanese Participants With Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma (R/M cSCC) or Locally Advanced (LA) Unresectable cSCC (MK-3475A-E39)

• ClinicalTrials.gov Identifier: NCT06041802
• Recruitment Status: Recruiting
• First Posted: September 18, 2023
• Last Update Posted: April 22, 2024
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: September 11, 2023
• First Posted Date: September 18, 2023
• Last Update Posted Date: April 22, 2024
• Actual Study Start Date: October 20, 2023
• Estimated Primary Completion Date: March 2, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 11, 2023)

Objective Response Rate (ORR) [ Time Frame: Up to approximately 40 months ]

ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 7, 2023)

• Duration of Response (DOR) [ Time Frame: Up to approximately 40 months ]
  For participants who demonstrate CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 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 at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented.
• Disease Control Rate (DCR) [ Time Frame: Up to approximately 40 months ]
  DCR is defined, per RECIST 1.1, as the percentage of participants who demonstrate a confirmed CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of diameters of target lesions), or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD [at least a 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 at least 5 mm. The appearance of one or more new lesions is also considered PD.]).The DCR as assessed by BICR will be presented.
• Overall Survival (OS) [ Time Frame: Up to approximately 40 months ]
  OS is defined as the time from first dose of study treatment to death due to any cause.
• Number of Participants who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 28 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 number of participants who experience at least one AE will be reported.
• Number of Participants who Discontinue Due to an AE [ Time Frame: Up to approximately 25 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 number of participants who discontinue study treatment due to an AE will be reported.

Original Secondary Outcome Measures (submitted: September 11, 2023)

• Duration of Response (DOR) [ Time Frame: Up to approximately 40 months ]
  For participants who demonstrate CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 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 at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented.
• Disease Control Rate (DCR) [ Time Frame: Up to approximately 40 months ]
  DCR is defined, per RECIST 1.1, as the percentage of participants who demonstrate a confirmed CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of diameters of target lesions), or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD [at least a 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 at least 5 mm. The appearance of one or more new lesions is also considered PD.]).The DCR as assessed by BICR will be presented.
• Overall Survival (OS) [ Time Frame: Up to approximately 40 months ]
  OS is defined as the time from first dose of study treatment to death due to any cause.
• Number of Participants who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 30 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 number of participants who experience at least one AE will be reported.
• Number of Participants who Discontinue Due to an AE [ Time Frame: Up to approximately 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 number of participants who discontinue study treatment due to an AE will be reported.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of MK-3475A (Pembrolizumab Formulated With MK-5180) in Japanese Participants With Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma (R/M cSCC) or Locally Advanced (LA) Unresectable cSCC (MK-3475A-E39)
• Official Title: A Phase 2 Clinical Study to Evaluate the Safety and Efficacy of MK-3475A in Japanese Participants With Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma (R/M cSCC) or Locally Advanced (LA) Unresectable cSCC.
• Brief Summary: The purpose of this study is to evaluate the efficacy, safety, and tolerability of subcutaneous (SC) MK-3475A in Japanese participants with recurrent or metastatic cutaneous squamous cell carcinoma or locally advanced unresectable cSCC. The primary hypothesis is that MK-3475A will result in greater than 10% objective response rate (ORR) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Squamous Cell Carcinoma

Intervention

Biological: MK-3475A

MK-3475A is a fixed-dose formulation of pembrolizumab and MK-5180 for SC administration.

Study Arms

Experimental: MK-3475A

Participants will receive MK-3475A subcutaneously for up to 18 administrations.

Intervention: Biological: MK-3475A

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 11, 2023): 19
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2, 2027
• Estimated Primary Completion Date: March 2, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

The key inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

• Has histologically confirmed cSCC by the investigator as the primary site of malignancy
• R/M cSCC cohort only: Has metastatic disease, defined as disseminated disease distant to the initial/primary site of diagnosis, and/or has locally recurrent disease that has been previously treated (with either surgery or radiotherapy) and is not curable by either surgery or radiotherapy
• LA unresectable cSCC cohort only: Is ineligible for surgical resection
• LA unresectable cSCC cohort only: Has received prior radiation therapy (RT) to index site or has been deemed to be not eligible for RT
• LA unresectable cSCC cohort only: Has received prior systemic therapy for curative intent are eligible regardless of regimen
• Has a life expectancy of greater than 3 months
• Must provide archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated

Exclusion Criteria:

• Has cSCC that can be cured with surgical resection, radiotherapy, or with a combination of surgery and radiotherapy.
• Has any other histologic type of skin cancer other than invasive squamous cell carcinoma as the primary disease under study
• Has received prior systemic anticancer therapy including investigation agents within 4 weeks before allocation
• Has not adequately recovered from major surgery or has ongoing surgical complications
• Received prior radiotherapy within 2 weeks of study intervention, or had radiation-related toxicities, requiring corticosteroids
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• Known additional malignancy that is progressing or has required active treatment within the past 2 years
• Has an ongoing active infection requiring systemic therapy
• Has a history of human immunodeficiency virus (HIV) infection
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has history of allogenic tissue/organ transplant

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Toll Free Number; 1-888-577-8839; Trialsites@merck.com

• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT06041802
• Other Study ID Numbers: 3475A-E39; MK-3475A-E39 ( Other Identifier: Merck ); jRCT2041230074 ( Registry Identifier: Japan Registry of Clinical Trials (jRCT) )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• 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: April 2024