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Study of Pembrolizumab (MK-3475) in Adults With Recurrent/Metastatic Cutaneous Squamous Cell Carcinoma (cSCC) or Locally Advanced Unresectable cSCC (MK-3475-629/KEYNOTE-629)

NCT03284424

Description:

The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) in adult participants with recurrent or metastatic(R/M) cutaneous Squamous Cell Carcinoma (cSCC) or locally advanced (LA) unresectable cSCC that is not amenable to surgery and/or radiation and/or systemic therapies.

Related Conditions:
  • Skin Squamous Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Pembrolizumab (MK-3475) in Adults With Recurrent/Metastatic Cutaneous Squamous Cell Carcinoma (cSCC) or Locally Advanced Unresectable cSCC (MK-3475-629/KEYNOTE-629)
  • Official Title: A Phase 2, Open-Label, Single Arm Study to Evaluate the Safety and Efficacy of Pembrolizumab in Participants With Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma (R/M cSCC)

Clinical Trial IDs

  • ORG STUDY ID: 3475-629
  • SECONDARY ID: 2017-000594-37
  • SECONDARY ID: MK-3475-629
  • NCT ID: NCT03284424

Conditions

  • Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
PembrolizumabMK-3475R/M cSCC cohort

Purpose

The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) in adult participants with recurrent or metastatic(R/M) cutaneous Squamous Cell Carcinoma (cSCC) or locally advanced (LA) unresectable cSCC that is not amenable to surgery and/or radiation and/or systemic therapies.

Trial Arms

NameTypeDescriptionInterventions
R/M cSCC cohortExperimentalParticipants with R/M cSCC receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to approximately 2 years.
  • Pembrolizumab
LA cSCC cohortExperimentalParticipants with LA cSCC receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to approximately 2 years.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  R/M cSCC cohort only:

          -  Has cSCC that is either metastatic defined as disseminated disease, and/or
             unresectable disease that is not curable by surgery, radiation, or systemic therapy.

          -  Has histologically-confirmed cSCC as the primary site of malignancy (metastatic skin
             involvement from another primary cancer or from an unknown primary cancer is not
             permitted).

          -  LA cSCC cohort only:

          -  Must be ineligible for surgical resection.

          -  Participants who received prior radiation therapy (RT) to index site or must be deemed
             to be not eligible for RT unless the lesion has grown since receiving the RT.

          -  Participants who received prior systemic therapy for curative intent are eligible
             regardless of regimen.

          -  R/M cSCC cohort only:

          -  Has metastatic disease defined as disseminated disease distant to the initial/primary
             site of diagnosis, and/or must have locally recurrent disease that has been previously
             treated (with either surgery, radiotherapy, or systemic therapy), and is not amenable
             to either curative surgery, radiotherapy, or concurrent chemoradiotherapy treatment.

          -  Has measurable disease based on RECIST 1.1 as assessed by the central imaging vendor.

          -  Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within
             10 days prior to the start of study treatment.

          -  Has adequate organ function.

          -  Has a tissue sample adequate for programmed death-ligand 1 (PD-L1) testing as
             determined by central laboratory testing prior to study allocation.

          -  Has a life expectancy >3 months.

          -  Female participants of childbearing potential must agree to use an adequate method of
             contraception during the study treatment period and for at least 120 days after the
             last dose of study treatment.

        Exclusion Criteria:

          -  Has cSCC that is amenable to surgical resection, local control with radiotherapy, or
             local control with a combination of surgery and radiotherapy, or chemoradiotherapy.

          -  Has any other histologic type of skin cancer other than invasive squamous cell
             carcinoma as the primary disease under study, e.g. basal cell carcinoma that has not
             been definitively treated with surgery or radiation, Bowen's disease, Merkel cell
             carcinoma (MCC), melanoma.

          -  Has had any prior allogeneic solid organ or bone marrow transplantation.

          -  Has received prior therapy with an anti-programmed death protein-1 (anti-PD-1),
             anti-programmed death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent
             directed to another stimulatory or co-inhibitory T cell receptor (e.g. cytotoxic
             T-lymphocyte associated protein 4 [CTLA-4], Tumor necrosis factor receptor
             superfamily, member 4 [OX-40], tumor necrosis factor receptor superfamily member 9
             [CD137]).

          -  Has received prior systemic anti-cancer therapy including investigational agents
             within 4 weeks prior to study allocation.

        (Notes: Participants must have recovered from all AEs due to previously administered
        therapies to ≤ Grade 1 or baseline. If a participant received major surgery, they must have
        recovered adequately from the toxicity and/or complications from the intervention prior to
        starting study treatment.)

          -  Has received prior radiotherapy within 2 weeks of start of study treatment.

          -  Is currently participating in or has participated in a study of an investigational
             agent or has used an investigational device within 4 weeks prior to the first dose of
             study treatment.

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis.

          -  Has an active autoimmune disease that has required systemic treatment in the past 2
             years (e.g. with use of disease-modifying agents, anticoagulants, corticosteroids or
             immunosuppressive drugs).

          -  Has a history of (noninfectious) pneumonitis that required steroids or has current
             pneumonitis.

          -  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 known active Hepatitis C virus infection.

          -  Is pregnant or breastfeeding or expecting to conceive or father children within the
             projected duration of the study, starting with the screening visit through 120 days
             after the last dose of study treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Up to approximately 24 months
Safety Issue:
Description:ORR is defined as the percentage of participants who have best response of 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, taking as reference the baseline sum diameters) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR).

Secondary Outcome Measures

Measure:Duration of Response (DOR)
Time Frame:Up to approximately 24 months
Safety Issue:
Description:For participants who demonstrate a CR (Disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters), DOR is defined as the time from first documented evidence of CR or PR per RECIST 1.1 as assessed by BICR until progressive disease (PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.) per RECIST 1.1 as assessed by BICR or death due to any cause, whichever occurs first.
Measure:Disease Control Rate (DCR)
Time Frame:Up to approximately 24 months
Safety Issue:
Description:DCR is defined as the percentage of participants who have CR (Disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) 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 and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.]) for at least 12 weeks per RECIST 1.1 as assessed by BICR.
Measure:Progression-free Survival (PFS)
Time Frame:Up to approximately 24 months
Safety Issue:
Description:PFS is defined as the time from first day of study treatment to the first documented PD (At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.] per RECIST 1.1 as assessed by BICR or death due to any cause, whichever occurs first.
Measure:Overall Survival (OS)
Time Frame:Up to approximately 24 months
Safety Issue:
Description:OS is defined as the time from first day of study treatment to death due to any cause.
Measure:Adverse Events (AEs)
Time Frame:Up to approximately 27 months
Safety Issue:
Description:An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience one or more AEs will be presented.
Measure:Study Treatment Discontinuations Due to AEs
Time Frame:Up to approximately 24 months
Safety Issue:
Description:An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be presented.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • PD1
  • PD-1
  • PDL1
  • PD-L1

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