Solid Tumor Clinical Trial
Official title:
A Multicenter, Randomized, Double-Blind, Phase 2, Basket Study of MK-4280A, a Coformulation of Favezelimab (MK-4280) With Pembrolizumab (MK-3475) in Selected Solid Tumors (KeyForm-010)
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].
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 |
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 |
Lead Sponsor | Collaborator |
---|---|
Merck Sharp & Dohme LLC |
United States, Australia, Canada, France, Germany, Italy, Malaysia, Netherlands, Taiwan, Turkey,
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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