Hodgkin Lymphoma Clinical Trial
Official title:
A Phase 3 Randomized Clinical Study of MK-4280A (Coformulated Favezelimab [MK-4280] Plus Pembrolizumab [MK-3475]) Versus Physician's Choice Chemotherapy in PD-(L)1-refractory, Relapsed or Refractory Classical Hodgkin Lymphoma (KEYFORM-008)
The purpose of this study is to compare efficacy of coformulated favezelimab/pembrolizumab (MK-4280A) with physician's choice chemotherapy of bendamustine or gemcitabine in participants with PD-(L)1-refractory, relapsed or refractory classical Hodgkin Lymphoma. The study will also assess the safety and tolerability of coformulated favezelimab/pembrolizumab. The primary study hypotheses are that coformulated favezelimab/pembrolizumab is superior to physician's choice chemotherapy with respect to progression-free survival (PFS) and overall survival (OS).
| Status | Recruiting |
| Enrollment | 360 |
| Est. completion date | June 16, 2031 |
| Est. primary completion date | May 25, 2027 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - Has histologically confirmed diagnosis of classical Hodgkin lymphoma (cHL) that is 2-fluorodeoxyglucose-avid (FDG-avid). - Has relapsed (defined as disease progression after most recent therapy) or refractory (defined as failed to achieve CR or PR to most recent therapy) cHL and exhausted all available treatment options with known clinical benefit. - Has progressed on treatment with an anti-PD-(L)1 monoclonal antibody (mAb) administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. - Submits an archival (<5 years) or newly obtained tumor tissue sample which has not been previously irradiated. Exclusion Criteria: - Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy. - History of central nervous system (CNS) metastases or active CNS involvement. - Has an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy. - History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. - Has an active infection requiring systemic treatment. - History of hemophagocytic lymphohisticytosis. - Has an active seizure disorder that is not well controlled. - Has clinically significant (ie, active) cardiovascular disease. - Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization. - Received prior radiotherapy within 2 weeks of start of study intervention or radiation related toxicities requiring corticosteroids. - Has not adequately recovered from major surgical procedure. - Known additional malignancy that is progressing or has required active treatment within the past 3 years. - History of human immunodeficiency virus (HIV). - Has had an allogeneic hematopoietic stem cell or solid organ transplantation within the last 5 years. |
| Country | Name | City | State |
|---|---|---|---|
| Argentina | Hospital Aleman-oncohematologic diseases ( Site 2302) | Buenos Aires | Caba |
| Australia | Royal Adelaide Hospital ( Site 0005) | Adelaide | South Australia |
| Australia | Royal Perth Hospital-Haematology ( Site 0004) | Perth | Western Australia |
| Australia | Western Health-Sunshine & Footscray Hospitals-Cancer Services-Cancer Research ( Site 0002) | St Albans | Victoria |
| Australia | The Townsville Hospital ( Site 0006) | Townsville | Queensland |
| Belgium | UZ Leuven-Hematology ( Site 0101) | Leuven | Vlaams-Brabant |
| Belgium | Université Catholique de Louvain-Namur - Centre Hospitalier Universitaire Dinant-Godinne - Site Godi | Yvoir | Namur |
| Brazil | Fundação Pio XII - Hospital de Câncer de Barretos ( Site 0202) | Barretos | Sao Paulo |
| Brazil | Hospital Paulistano-Americas Oncologia ( Site 0207) | Sao Paulo | |
| Canada | Jewish General Hospital ( Site 0309) | Montreal | Quebec |
| Chile | Clínica Inmunocel ( Site 0407) | Santiago | Region M. De Santiago |
| Chile | FALP-UIDO ( Site 0400) | Santiago | Region M. De Santiago |
| China | Beijing Hospital ( Site 0514) | Beijing | Beijing |
| China | Peking University Third Hospital-Hematology ( Site 0519) | Beijing | Beijing |
| China | The First Hospital of Jilin University-Hematology ( Site 0516) | Changchun | Jilin |
| China | Hunan Cancer Hospital ( Site 0503) | Changsha | Hunan |
| China | Xiangya Hospital Central South University ( Site 0513) | Changsha | Hunan |
| China | West China Hospital of Sichuan University-Head and Neck Oncology ( Site 0502) | Cheng Du | Sichuan |
| China | Sun Yat-sen University Cancer Center-Internal medicine ( Site 0500) | Guangzhou | Guangdong |
| China | Zhejiang Cancer Hospital ( Site 0510) | Hangzhou | Zhejiang |
| China | Anhui Provincial Cancer Hospital ( Site 0501) | Hefei | Anhui |
| China | Ningbo First Hospital ( Site 0518) | Ningbo | Zhejiang |
| China | Fudan University Shanghai Cancer Center ( Site 0520) | Shanghai | Shanghai |
| China | Tianjin Medical University Cancer Institute & Hospital-lymphoma ( Site 0506) | Tianjin | Tianjin |
| China | Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 0509) | Wuhan | Hubei |
| China | The First Affiliated hospital of Xiamen University ( Site 0512) | Xiamen | Fujian |
| China | Henan Cancer Hospital ( Site 0515) | Zhengzhou | Henan |
| Czechia | Fakultní nemocnice Brno Bohunice-Interni hematologicka a onkologicka klinika ( Site 0901) | Brno | Brno-mesto |
| Czechia | Fakultni nemocnice Hradec Kralove-IV. interni hematologicka klinika ( Site 0902) | Hradec Kralove | |
| Czechia | Vseobecna fakultni nemocnice v Praze-I. Interní klinika - klinika hematologie ( Site 0903) | Praha 2 | |
| France | HENRI MONDOR HOSPITAL ( Site 0702) | Créteil | Seine-et-Marne |
| France | Centre Hospitalier Universitaire de Limoges - Hôpital Dupuytren ( Site 0704) | Limoges | Haute-Vienne |
| France | CENTRE LEON BERARD-Medical oncology ( Site 0703) | Lyon | Rhone |
| France | Institut Universitaire du Cancer Toulouse - Oncopole - CHU de TOULOUSE ( Site 0706) | Toulouse | Haute-Garonne |
| Germany | Universitaetsklinikum Carl Gustav Carus Dresden-University Cancer Center Early Clinical Trial Unit ( | Dresden | Sachsen |
| Germany | Universitaetsklinikum Koeln-Klinik I für Innere Medizin ( Site 0801) | Köln | Nordrhein-Westfalen |
| Germany | Universitätsklinikum Leipzig ( Site 0803) | Leipzig | Sachsen |
| Germany | Universitätsklinikum Münster - Albert Schweitzer Campus ( Site 0806) | Münster | Nordrhein-Westfalen |
| Germany | Klinikum Stuttgart - Katharinenhospital ( Site 0804) | Stuttgart | Baden-Wurttemberg |
| Germany | Universitaetsklinikum Ulm-Department of Internal Medicine III ( Site 0805) | Ulm | Baden-Wurttemberg |
| Israel | Carmel Hospital ( Site 1007) | Haifa | |
| Israel | Rambam Health Care Campus ( Site 1004) | Haifa | |
| Israel | Hadassah Medical Center-Hemato-Oncology ( Site 1000) | Jerusalem | |
| Israel | Rabin Medical Center-Hemato-Oncology ( Site 1001) | Petah-Tikva | |
| Israel | Sheba Medical Center-Hemato Oncology ( Site 1005) | Ramat Gan | |
| Israel | Sourasky Medical Center ( Site 1002) | Tel Aviv | |
| Korea, Republic of | Pusan National University Hospital-Internal Medicine ( Site 1704) | Busan | Pusan-Kwangyokshi |
| Korea, Republic of | Asan Medical Center-Department of Oncology ( Site 1703) | Seoul | |
| Korea, Republic of | Samsung Medical Center ( Site 1700) | Seoul | |
| Korea, Republic of | Seoul National University Hospital ( Site 1701) | Seoul | |
| Korea, Republic of | Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1702) | Seoul | |
| Poland | Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 1402) | Gdansk | Pomorskie |
| Poland | Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie-Oncology Department ( Site 1406) | Kraków | Malopolskie |
| Poland | Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Kilinka Onkologii I Hematologii ( Site | Warszawa | Mazowieckie |
| Poland | Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckieg-Klinika Hematologii, Nowotworów Krwi i | Wroclaw | Dolnoslaskie |
| Spain | CHUAC-Complejo Hospitalario Universitario A Coruña ( Site 1812) | A Coruña | La Coruna |
| Spain | Hospital General Universitario de Alicante ( Site 1806) | Alicante | |
| Spain | Hospital Universitari Vall d'Hebron ( Site 1803) | Barcelona | Cataluna |
| Spain | Hospital Insular de Gran Canaria-Oncology ( Site 1807) | Las Palmas de Gran Canaria | Las Palmas |
| Spain | Hospital Universitario 12 de Octubre-Hemathology and hemotherapy ( Site 1810) | Madrid | |
| Spain | Hospital Universitario Virgen de la Victoria ( Site 1808) | Malaga | |
| Spain | Hospital Universitario de Salamanca - Complejo Asistencial U-Servicio de Hematologia ( Site 1801) | Salamanca | |
| Spain | Hospital Universitario Marqués de Valdecilla ( Site 1805) | Santander | Cantabria |
| Sweden | Skånes Universitetssjukhus Lund ( Site 1901) | Lund | Skane Lan |
| Sweden | Akademiska sjukhuset-Blod- och tumörsjukdomar ( Site 1900) | Uppsala | Uppsala Lan |
| Switzerland | Ospedale Regionale Bellinzona e Valli-IOSI ( Site 1600) | Bellinzona | Ticino |
| Turkey | Ankara Universitesi Tip Fakultesi Hastanesi-hematology ( Site 2000) | Ankara | |
| Turkey | Hacettepe Universite Hastaneleri-Department of Hematology ( Site 2006) | Ankara | |
| Turkey | Antalya Egitim ve Arastirma Hastanesi ( Site 2011) | Antalya | |
| Turkey | Ege Universitesi Hastanesi ( Site 2001) | Izmir | |
| Turkey | Kocaeli Üniversitesi-Hematology ( Site 2009) | Kocaeli | |
| Turkey | Mega Medipol-Hematology ( Site 2005) | Stanbul | Istanbul |
| United Kingdom | The Beatson West of Scotland Cancer Centre ( Site 2110) | Glasgow | Glasgow City |
| United Kingdom | St James's University Hospital ( Site 2109) | Leeds | |
| United Kingdom | Leicester Royal Infirmary ( Site 2100) | Leicester | |
| United Kingdom | Clatterbridge Cancer Centre - Liverpool-Heamatology ( Site 2108) | Liverpool | |
| United Kingdom | St Bartholomew's Hospital-Centre for Experimental Cancer Medicine ( Site 2105) | London | London, City Of |
| United Kingdom | GenesisCare - Oxford ( Site 2104) | Oxford | Oxfordshire |
| United Kingdom | Derriford Hospital ( Site 2107) | Plymouth | Devon |
| United States | University of Michigan ( Site 2215) | Ann Arbor | Michigan |
| United States | Johns Hopkins University-The Sidney Kimmel Comprehensive Cancer Center ( Site 2206) | Baltimore | Maryland |
| United States | University of Maryland-Greenebaum Comprehensive Cancer Center ( Site 2210) | Baltimore | Maryland |
| United States | Cleveland Clinic-Taussig Cancer Center ( Site 2203) | Cleveland | Ohio |
| United States | University Hospitals Cleveland Medical Center ( Site 2214) | Cleveland | Ohio |
| United States | University of Kentucky Chandler Medical Center ( Site 2201) | Lexington | Kentucky |
| United States | UCLA Hematology/Oncology - Santa Monica ( Site 2208) | Los Angeles | California |
| United States | Rutgers Cancer Institute of New Jersey ( Site 2217) | New Brunswick | New Jersey |
| United States | AHN West Penn Hospital ( Site 2213) | Pittsburgh | Pennsylvania |
| United States | UPMC Hillman Cancer Center ( Site 2205) | Pittsburgh | Pennsylvania |
| United States | Fred Hutchinson Cancer Center ( Site 2212) | Seattle | Washington |
| United States | The University of Arizona Cancer Center - North Campus ( Site 2216) | Tucson | Arizona |
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme LLC |
United States, Argentina, Australia, Belgium, Brazil, Canada, Chile, China, Czechia, France, Germany, Israel, Korea, Republic of, Poland, Spain, Sweden, Switzerland, Turkey, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Progression Free Survival (PFS) per Lugano Response Criteria as Assessed by Blinded Independent Central Review (BICR) | PFS is defined as the time from randomization to the first documented disease progression per Lugano criteria 2014 as assessed by BICR or death due to any cause, whichever occurs first. | Up to approximately 43 months | |
| Secondary | Overall Survival (OS) | OS is defined as the time from randomization to death due to any cause. | Up to approximately 105 months | |
| Secondary | Objective Response Rate (ORR) per Lugano Response Criteria as Assessed by BICR | ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) per Lugano criteria 2014 as assessed by BICR. | Up to approximately 25 months | |
| Secondary | Duration of Response (DOR) per Lugano Response Criteria as Assessed by BICR | For participants who demonstrate CR or PR per Lugano criteria 2014 as assessed by BICR, DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. | Up to approximately 43 months | |
| Secondary | Number of Participants Who Experienced At Least One Adverse Event (AE) | An AE is any untoward medical occurrence in a clinical study participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be presented. | Up to approximately 27 months | |
| Secondary | Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) | An AE is any untoward medical occurrence in a clinical study participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be presented. | Up to approximately 24 months |
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|---|---|---|---|
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