NCT03284424 · CITED IN SOURCE DOCUMENTS

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)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2024-08-23

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Objective Response Rate (ORR)

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outcome · POSTED

Duration of Response (DOR)

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outcome · POSTED

Disease Control Rate (DCR)

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outcome · POSTED

Progression-free Survival (PFS)

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Number of Participants Who Experienced One or More Adverse Events (AEs)

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outcome · POSTED

Number of Participants Who Discontinued Study Treatment Due to AE

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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 or radiation. * 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. * 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 or radiotherapy), and is not amenable to either curative surgery or radiotherapy. * 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 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, 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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants 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.
intervention Names
Biological: Pembrolizumab
label
R/M cSCC cohort
type
EXPERIMENTAL
description
Participants with LA cSCC receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to approximately 2 years.
intervention Names
Biological: Pembrolizumab
label
LA cSCC cohort
type
EXPERIMENTAL

interventions

arm Group Labels
LA cSCC cohort
R/M cSCC cohort
description
IV infusion
name
Pembrolizumab
other Names
KEYTRUDA®
MK-3475
type
BIOLOGICAL

Study design

allocation

NON_RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 159
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
ORR was 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). ORR per RECIST 1.1 as assessed by blinded independent central review (BICR) is presented.
measure
Objective Response Rate (ORR)
time Frame
Up to approximately 32 months

secondary Outcomes

description
For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. The DOR per RECIST 1.1 as assessed by BICR is presented for all participants who experienced a confirmed CR or PR.
measure
Duration of Response (DOR)
time Frame
Up to approximately 56 months
description
DCR is defined as the percentage of participants who have a CR or PR or Stable Disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease). The DCR per RECIST 1.1 as assessed by BICR is presented.
measure
Disease Control Rate (DCR)
time Frame
Up to approximately 56 months
description
PFS was defined as the time from first dose of study treatment to the first documented PD or death due to any cause, whichever occurred first. PFS per RECIST 1.1 as assessed by BICR is presented.
measure
Progression-free Survival (PFS)
time Frame
Up to approximately 56 months
description
OS was defined as the time from first dose of study treatment to death due to any cause. The OS for all participants is presented.
measure
Overall Survival (OS)
time Frame
Up to approximately 56 months
description
An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy. The number of participants who experienced an AE is presented.
measure
Number of Participants Who Experienced One or More Adverse Events (AEs)
time Frame
Up to approximately 56 months
description
An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy. The number of participants who discontinued study treatment due to an AE is presented.
measure
Number of Participants Who Discontinued Study Treatment Due to AE
time Frame
Up to approximately 56 months

Full study description

brief Summary: 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.

Source references

references

citation
Grob JJ, Gonzalez R, Basset-Seguin N, Vornicova O, Schachter J, Joshi A, Meyer N, Grange F, Piulats JM, Bauman JR, Zhang P, Gumuscu B, Swaby RF, Hughes BGM. Pembrolizumab Monotherapy for Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Arm Phase II Trial (KEYNOTE-629). J Clin Oncol. 2020 Sep 1;38(25):2916-2925. doi: 10.1200/JCO.19.03054. Epub 2020 Jul 16.
pmid
32673170
type
RESULT
citation
Bratland A, Munoz-Couselo E, Mortier L, Roshdy O, Gonzalez R, Schachter J, Arance AM, Grange F, Meyer N, Joshi AJ, Billan S, Hughes BGM, Grob JJ, Ramakrishnan K, Ge J, Gumuscu B, Swaby RF, Gutzmer R. Health-Related Quality of Life with Pembrolizumab in Patients with Locally Advanced or Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma: KEYNOTE-629. Dermatol Ther (Heidelb). 2023 Dec;13(12):3165-3180. doi: 10.1007/s13555-023-01059-y. Epub 2023 Nov 9.
pmid
37943491
type
DERIVED
citation
Hughes BGM, Mendoza RG, Basset-Seguin N, Vornicova O, Schachter J, Joshi A, Meyer N, Grange F, Piulats JM, Bauman JR, Chirovsky D, Zhang P, Gumuscu B, Swaby RF, Grob JJ. Health-Related Quality of Life of Patients with Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma Treated with Pembrolizumab in KEYNOTE-629. Dermatol Ther (Heidelb). 2021 Oct;11(5):1777-1790. doi: 10.1007/s13555-021-00598-6. Epub 2021 Sep 23.
pmid
34558040
type
DERIVED