Clinical trial NCT03783078: Pembrolizumab (MK-3475) as First-line Therapy for Advanced Merkel Cell Carcinoma (MK-3475-913)
Official title: A Phase 3 Open-label, Single Arm Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) as First Line Therapy in Participants With Advanced Merkel Cell Carcinoma (KEYNOTE-913)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Merkel Cell Carcinoma
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1)
Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Merkel cell carcinoma
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2018-12-20
Enrollment: 55
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-arm, open-label, multicenter, efficacy, and safety study of pembrolizumab in adult and pediatric participants with previously untreated advanced Merkel Cell Carcinoma (MCC). The primary objective of the trial is to assess the objective response rate, as assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, following administration of pembrolizumab.


Eligibility criteria: Inclusion Criteria:

* Be male or female and at least 12 years of age, at the time of signing the informed consent/assent.
* Have histologically confirmed diagnosis of locoregional MCC that has recurred following standard locoregional therapy with surgery and/or radiation therapy and is not amenable to local therapy or metastatic MCC (Stage IV) as per American Joint Committee on Cancer (AJCC) 8th edition guidelines.
* Have been untreated for advanced or metastatic disease except as follows:

  1. Prior intratumoral therapy will be permitted.
  2. Prior adjuvant or neoadjuvant therapy containing systemic chemotherapy will be permitted if treatment concluded at least 3 months prior to Cycle 1 Day 1 (C1D1).
  3. Prior adjuvant or neoadjuvant therapy containing anti-PD-1/L1 or anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) therapy will not be permitted.
* Have at least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 criteria as determined by the local site investigator/radiology assessment.
* Toxic effect(s) of the most recent prior therapy have resolved to Grade 1 or less (except alopecia).
* Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
* Is not a woman of childbearing potential (WOCBP)
* OR
* Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis).
* A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 72 hours before the first dose of study intervention.
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or Lansky Play-Performance Scale (LPS) ≥50 for pediatric participants up to and including 16 years of age.
* Have adequate organ function

Exclusion Criteria:

* Has a known additional malignancy that is progressing or has required active treatment within the past 2 years with certain exceptions.
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis with certain exceptions.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to C1D1.
* Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
* Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids or immunosuppressive drugs).
* Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
* Has an active infection requiring systemic therapy.
* Has a known history of human immunodeficiency virus (HIV) infection.
* Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection.
* Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
* Has clinically significant cardiac disease within 6 months of C1D1, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
* Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
* Has not received standard locoregional therapy with surgery and/or radiation therapy for the treatment of local or locoregional disease. Note: This exclusion criterion does not apply to participants who are diagnosed with unresectable or metastatic MCC.
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor.
* Has received prior systemic anticancer therapy including investigational agents within 12 weeks prior to C1D1.
* Has received radiotherapy within 2 weeks prior to start of study intervention.
* Has received a live vaccine within 30 days prior to C1D1.
* 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 C1D1.
* Has had an allogenic tissue/solid organ transplant.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to ~34 months
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: Up to ~58 months
measure: Progression-free Survival (PFS)
timeFrame: Up to ~58 months
measure: Overall Survival (OS)
timeFrame: Up to ~58 months
measure: Number of Participants With One or More Adverse Events (AEs)
timeFrame: Up to ~58 months
measure: Number of Participants Who Discontinued From Study Treatment Due to an AE
timeFrame: Up to ~27 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0006)
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai ( Site 0004)
state: New York
city: North Sydney
country: Australia
facility: Melanoma Institute Australia ( Site 0400)
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle ( Site 0402)
state: New South Wales
city: Moncton
country: Canada
facility: Moncton Hospital - Horizon Health Network ( Site 0055)
state: New Brunswick
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre ( Site 0051)
state: Ontario
city: Caen
country: France
facility: Hopital de la Cote de Nacre - Caen ( Site 0204)
state: Calvados
city: Bordeaux
country: France
facility: CHU de Bordeaux- Hopital Saint Andre ( Site 0203)
state: Gironde
city: Boulogne-Billancourt
country: France
facility: Hopital Ambroise Pare Boulogne ( Site 0201)
state: Hauts-de-Seine
city: Chambray Les Tours
country: France
facility: C.H.R.U. de Tours. Hopital Trousseau ( Site 0202)
state: Indre-et-Loire
city: Lille
country: France
facility: CHRU Lille - Hopital Claude Huriez ( Site 0200)
state: Nord
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese ( Site 0224)
state: Toscana
city: Milano
country: Italy
facility: IEO Istituto Europeo di Oncologia ( Site 0223)
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione Pascale ( Site 0222)
city: Padova
country: Italy
facility: Istituto Oncologico Veneto ( Site 0221)
city: Auckland
country: New Zealand
facility: Auckland City Hospital ( Site 0427)
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia ( Site 0262)
state: Valenciana, Comunitat
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron ( Site 0264)
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona ( Site 0261)
city: Madrid
country: Spain
facility: Hospital Universitario La Paz ( Site 0263)
city: Solna
country: Sweden
facility: Karolinska Universitetssjukhuset Solna ( Site 0281)
state: Stockholms Lan
city: Goeteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset ( Site 0282)
state: Vastra Gotalands Lan
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Mortier L, Villabona L, Lawrence B, Arance A, Butler MO, Beylot-Barry M, Saiag P, Samimi M, Ascierto PA, Spada F, De Pontville M, Maio M, Berrocal A, Espinosa E, Capdevila J, Levin M, Das D, Krepler C, Grebennik D, Chiarion-Sileni V. Pembrolizumab for the First-Line Treatment of Recurrent Locally Advanced or Metastatic Merkel Cell Carcinoma: Results from the Single-Arm, Open-Label, Phase III KEYNOTE-913 Study. Am J Clin Dermatol. 2024 Nov;25(6):987-996. doi: 10.1007/s40257-024-00885-w. Epub 2024 Oct 8.