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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06036836
Other study ID # 4280A-010
Secondary ID MK-4280A-0102023
Status Recruiting
Phase Phase 2
First received
Last updated
Start date September 29, 2023
Est. completion date March 9, 2027

Study information

Verified date June 2024
Source Merck Sharp & Dohme LLC
Contact Toll Free Number
Phone 1-888-577-8839
Email Trialsites@merck.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to evaluate pathological complete response (pCR) rate of coformulated favezelimab/pembrolizumab (MK-4280A) or pembrolizumab as assessed by blinded central pathology review (BICR) in participants with cutaneous squamous cell carcinoma (cSCC) [Cohort A] and to evaluate lenvatinib in combination with coformulated favezelimab/pembrolizumab or pembrolizumab with respect to objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by investigator in participants proficient in mismatch repair (pMMR) endometrial cancer (EC) [Cohort B].


Recruitment information / eligibility

Status Recruiting
Enrollment 160
Est. completion date March 9, 2027
Est. primary completion date March 9, 2027
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria Cohort A only - Histologically confirmed diagnosis of resectable cutaneous squamous cell carcinoma (cSCC) as the primary site of malignancy (metastatic skin involvement from another primary cancer or from an unknown primary cancer is not permitted) - Stage II to Stage IV disease without distant metastasis (M1). cSCC tumors arising in the head and neck will be staged according to American Joint Committee on Cancer (AJCC) Edition (Ed.) 8 and cSCC tumors arising in non-head and neck locations will be staged according to Union for International Cancer Control (UICC) Ed. 8 - Is systemic treatment naïve - Archival tumor tissue sample, or newly obtained surgical resection, or biopsy sample of a tumor lesion not previously irradiated has been provided - Is an individual of any sex/gender, at least 18 years of age at the time of providing the informed consent Cohort B only - Histologically confirmed diagnosis of endometrial cancer (EC) that is not deficient in mismatch repair (dMMR) proficient in mismatch repair (pMMR) as documented by a local test report - Documented evidence of stage IVB (per 2009 International Federation of Gynecology and Obstetrics (FIGO) staging), recurrent, or metastatic EC, and are not candidates for curative surgery or radiation - Has radiographic evidence of disease progression after 1 prior systemic, platinum-based chemotherapy regimen for EC in any setting - Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST 1.1) by investigator (before first dose of study intervention) - Is assigned female sex at birth, at least 18 years of age at the time of providing the informed consent - Has adequately controlled blood pressure without antihypertensive medication All Cohorts - Agrees to follow contraception guidelines if a participant of childbearing potential - Has a life expectancy >3 years per investigator assessment - Has adequate organ function - Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - If positive for hepatitis B, has received antiviral therapy for =4 weeks and undetectable viral load prior to randomization - If positive for hepatitis C, has undetectable viral load at screening - If positive for human immunodeficiency virus (HIV), has well-controlled HIV on a stable highly active antiretroviral therapy Exclusion Criteria: All Cohorts - Has known hypersensitivity to active substances or their excipients including previous clinically significant hypersensitivity reaction to treatment with other monoclonal antibody (mAb) - History of allogeneic tissue/solid organ transplant Cohort A only - Received prior radiotherapy to the index lesion (in-field lesion) - Participants for whom the primary site of cSCC was anogenital area (penis, scrotum, vulva, perianal region) are not eligible Cohort B - Has had major surgery within 3 weeks prior to first dose of study interventions - Has preexisting =Grade 3 gastrointestinal or non-gastrointestinal fistula - Has urine protein =1 g/24 hours - Has a left ventricle ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multi-gated acquisition (MUGA) or echocardiogram (ECHO) - Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation - Has clinically significant cardiovascular disease within 12 months from first dose of study intervention

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
favezelimab/pembrolizumab
IV infusion
pembrolizumab
IV infusion
Drug:
lenvatinib
Oral administration of capsule

Locations

Country Name City State
Australia Royal Brisbane and Women's Hospital ( Site 0002) Brisbane Queensland
Australia St Vincent's Hospital-The Kinghorn Cancer Centre ( Site 0005) Darlinghurst New South Wales
Australia The Alfred Hospital ( Site 0004) Melbourne Victoria
Australia Fiona Stanley Hospital ( Site 0006) Murdock Western Australia
Australia Royal North Shore Hospital ( Site 0008) St Leonards New South Wales
Australia Blacktown Hospital ( Site 0003) Sydney New South Wales
Canada Jewish General Hospital ( Site 0605) Montreal Quebec
Canada Centre Hospitalier de l'Université de Montréal ( Site 0602) Montréal Quebec
Canada McGill University Health Centre ( Site 0604) Montréal Quebec
Canada Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0 Quebec City Quebec
Canada Princess Margaret Cancer Centre ( Site 0606) Toronto Ontario
Canada Sunnybrook Research Institute ( Site 0607) Toronto Ontario
France Centre Hospitalier Régional Universitaire de Brest - Hôpital Morvan ( Site 0154) Brest Finistere
France CENTRE LEON BERARD ( Site 0151) Lyon Cedex08 Rhone-Alpes
France Hopitaux Universitaires Paris Centre-Hopital Cochin ( Site 0155) Paris
France Institut de cancérologie Strasbourg Europe (ICANS) ( Site 0153) Strasbourg Alsace
Germany Universitaetsklinikum Essen-Klinik für Dermatologie, Venerologie und Allergologie ( Site 0182) Essen Nordrhein-Westfalen
Italy Fondazione IRCCS Istituto Nazionale dei Tumori-SC Oncologia Medica 3 - Tumori Testa-collo ( Site 025 Milan Lombardia
Italy Istituto Nazionale Tumori IRCCS Fondazione Pascale-s.c. melanoma, immunoterapia oncologica e terapi Napoli
Malaysia Hospital Sultan Ismail-Pusat Rawatan Radioterapi Dan Onkologi ( Site 0063) Johor Bahru Johor
Malaysia Sarawak General Hospital-Radiotherapy Unit ( Site 0062) Kuching Sarawak
Malaysia University Malaya Medical Centre ( Site 0061) Lembah Pantai Kuala Lumpur
Netherlands University Medical Center Groningen ( Site 0273) Groningen
Netherlands Radboudumc ( Site 0274) Nijmegen Gelderland
Netherlands Erasmus Medisch Centrum ( Site 0272) Rotterdam Zuid-Holland
Taiwan Taichung Veterans General Hospital-GYNECOLOGY ( Site 0033) Taichung
Taiwan National Cheng Kung University Hospital-Clinical Trial Center ( Site 0032) Tainan
Taiwan National Taiwan University Hospital ( Site 0031) Taipei
Turkey Ankara Bilkent Sehir Hastanesi ( Site 0427) Ankara
Turkey Gulhane Egitim Arastirma Hastanesi-Onkoloji ( Site 0424) Ankara
Turkey Hacettepe Universite Hastaneleri-oncology hospital ( Site 0421) Ankara
Turkey Liv Hospital Ankara-Oncology ( Site 0426) Ankara
Turkey TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 0423) Istanbul
Turkey Medipol Mega Universite Hastanesi-oncology ( Site 0425) Stanbul Istanbul
United States St. Luke's University Health Network ( Site 0636) Bethlehem Pennsylvania
United States Dana-Farber Cancer Institute ( Site 0642) Boston Massachusetts
United States Cleveland Clinic Main ( Site 0639) Cleveland Ohio
United States UT Southwestern Medical Center-CRO-Simmons Comprehensive Cancer Center ( Site 0645) Dallas Texas
United States Duke Cancer Institute ( Site 0641) Durham North Carolina
United States Rutgers Cancer Institute of New Jersey ( Site 0635) New Brunswick New Jersey
United States Yale-New Haven Hospital-Yale Cancer Center ( Site 0643) New Haven Connecticut
United States UPMC Hillman Cancer Center ( Site 0644) Pittsburgh Pennsylvania

Sponsors (1)

Lead Sponsor Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Italy,  Malaysia,  Netherlands,  Taiwan,  Turkey, 

Outcome

Type Measure Description Time frame Safety issue
Primary Pathological Complete Response (pCR) - Cohort A pCR is defined as complete absence of viable tumor in the surgical resection sample as assessed by central review of the pathology results. Number of Cohort A participants with pCR will be reported. Up to approximately 22 months
Primary Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Investigator - Cohort B The ORR is defined as the percentage of participants who have an OR per investigator assessment. The OR is defined as a 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. Up to approximately 21 months
Secondary Overall Survival (OS) - All Cohorts OS is defined as the time from randomization to death from any cause. Up to approximately 41 months
Secondary Clinical Benefit Rate - Cohort A Clinical benefit rate is defined as the percentage of participants who have clinical benefit. Clinical benefit is defined as pCR in participants who undergo surgery or clinical complete response (cCR) [defined as residual tumor not visible on clinical exam or on imaging and a negative biopsy, if biopsy is available, in participants who decline surgery. Up to approximately 22 months
Secondary Event-Free Survival (EFS) - Cohort A EFS is defined as the time from randomization to first progression prior to surgical resection as assessed by investigator, inability to resect tumor, recurrence (postsurgical resection), or death from any cause, whichever occurs first. Up to approximately 41 months
Secondary Major Pathological Response (mPR) - Cohort A mPR is defined as =10% of viable tumor cells in the surgical resection sample as assessed by central review of the pathology results. The number of Cohort A participants with mPR will be reported. Up to approximately 22 months
Secondary ORR per RECIST 1.1 as assessed by Investigator - Cohort A The ORR is defined as the percentage of participants who have an OR per investigator assessment. The OR is defined as a 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. Up to approximately 22 months
Secondary Number of participants with an adverse event (AE) - Cohorts A and B An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of participants who experience an AE will be reported. Up to approximately 41 months
Secondary Number of participants discontinuing from study therapy due to AE - Cohorts A and B An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of participants who discontinue study treatment due to an AE will be reported. Up to approximately 41 months
Secondary Number of participants experiencing perioperative complications - Cohort A The number of participants who experience perioperative complications will be assessed. Up to approximately 18 weeks
Secondary Number of participants with an AE that precludes surgery/initiation of adjuvant therapy - Cohort A An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of Cohort A participants with an AE that precludes surgery or initiation of adjuvant therapy will be reported. Up to approximately 2 months
Secondary Progression Free Survival (PFS) - Cohort B PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by the investigator. Per RECIST 1.1, or by histopathologic confirmation of disease progression (PD), 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. Unequivocal progression of non-target lesions is also considered PD. Up to approximately 41 months
Secondary Duration of Response (DOR) - Cohort B DOR is defined as the time from first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) 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 Blinded Independent Central Review (BICR) will be presented. Up to approximately 41 months
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