Melanoma Clinical Trial
Official title:
A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Design of Investigational Agents With or Without Pembrolizumab or Pembrolizumab Alone in Participants With Melanoma (KEYMAKER-U02): Substudy 02B
Substudy 02B is part of a larger research study that is testing experimental treatments for melanoma, a type of skin cancer. The larger study is the umbrella study. The goal of substudy 02B is to evaluate the safety and efficacy of investigational treatment arms in participants with 1L advanced melanoma and to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/pembrolizumab monotherapy. Arm 1: Pembrolizumab + Vibostolimab was added in the base protocol on 13-Nov-2019, and enrollment into this arm has been completed. Arm 2: Pembrolizumab was added in the base protocol on 13-Nov-2019, and enrollment stopped prematurely on 15-Aug-2022. Arm 3: Coformulation Pembrolizumab/Quavonlimab was added in Amendment 01 on 20-Oct-2020, and enrollment stopped prematurely on 15-Aug-2022. Arm 4: Coformulation Pembrolizumab/Quavonlimab + Lenvatinib was added in Amendment 01 on 20-Oct-2020, and enrollment is ongoing. Arm 5: Coformulation Favezelimab/Pembrolizumab, Arm 6: Coformulation Favezelimab/Pembrolizumab + All-trans Retinoic Acid (ATRA), and Arm 7: Coformulation Favezelimab/Pembrolizumab + Vibostolimab were added in Amendment 04 on 10-May-2023, and enrollment for these arms will be initiated in July 2023.
| Status | Recruiting |
| Enrollment | 315 |
| Est. completion date | April 3, 2030 |
| Est. primary completion date | April 3, 2030 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 120 Years |
| Eligibility | Inclusion Criteria: - Has histologically or cytologically confirmed melanoma - Has unresectable Stage III or Stage IV melanoma, not amenable to local therapy - Has been untreated for advanced disease. - Has provided a tumor biopsy - If capable of producing sperm, male participants agree to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention (7 days): - Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR - Uses contraception unless confirmed to be azoospermic - 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 WOCBP OR - Is a WOCBP and Uses a contraceptive method that is highly effective, with low user dependency, or be abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is: - MK-4280A: 120 days - MK-1308A: 120 days - MK-7684: 50 days - MK-3475: 120 days - Lenvatinib: 30 days - ATRA: 30 days - Has adequate organ function - Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia and Grade 2 neuropathy) Exclusion Criteria: - Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 7 days before the first dose of study intervention - Has a known additional malignancy that is progressing or requires active treatment within the past 2 years - Has known central nervous system (CNS) metastases and/or carcinomatous meningitis - Has ocular or mucosal melanoma - Has an active autoimmune disease that has required systemic treatment in the past 2 years - Has an active infection requiring systemic therapy - Has known history of human immunodeficiency virus (HIV) - Has history of Hepatitis B or known Hepatitis C virus infection - Has a history of (noninfectious) pneumonitis - Has a history of active tuberculosis (TB) - Has received prior systemic anticancer therapy within 4 weeks prior to randomization - Has received prior radiotherapy within 2 weeks of first dose of study intervention - Has had major surgery <3 weeks prior to first dose of study intervention - Has received a live vaccine within 30 days before the first dose of study intervention - Has participated in a study of an investigational agent within 4 weeks prior to the first dose of study intervention - Has had an allogeneic tissue/solid organ transplant - Has a known psychiatric or substance abuse disorder that would interfere with requirements of the study - Participants who receive lenvatinib have the following additional exclusion criteria: - Has a pre-existing Grade =3 gastrointestinal or non-gastrointestinal fistula - Has radiographic evidence of encasement of invasion of a major blood vessel, or of intratumoral cavitation - Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study intervention - Has clinically significant cardiovascular disease within 12 months from first dose of study intervention - Has urine protein =1 g/24-hour. - Has presence of gastrointestinal condition including malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib |
| Country | Name | City | State |
|---|---|---|---|
| Argentina | Sanatorio Finochietto ( Site 2245) | Buenos Aires | |
| Australia | Fiona Stanley Hospital ( Site 2401) | Murdoch | Western Australia |
| Australia | Tasman Oncology Research Pty Ltd ( Site 2403) | Southport | Queensland |
| Australia | Calvary Mater Newcastle-Medical Oncology ( Site 2404) | Waratah | New South Wales |
| Australia | Melanoma Institute Australia ( Site 2402) | Wollstonecraft | New South Wales |
| Chile | IC La Serena Research ( Site 2254) | La Serena | Coquimbo |
| Chile | Bradfordhill ( Site 2252) | Santiago | Region M. De Santiago |
| Chile | FALP-UIDO ( Site 2251) | Santiago | Region M. De Santiago |
| Chile | Oncovida ( Site 2257) | Santiago | Region M. De Santiago |
| Chile | CIDO SpA-Oncology ( Site 2256) | Temuco | Araucania |
| Colombia | Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia-Center Investigator ( Site 2261) | Bogota | Distrito Capital De Bogota |
| Colombia | Fundación Valle del Lili ( Site 2265) | Cali | Valle Del Cauca |
| France | CHU de Bordeaux- Hopital Saint Andre ( Site 2108) | Bordeaux | Gironde |
| France | Hopital La Timone ( Site 2103) | Marseille | Bouches-du-Rhone |
| France | A.P.H. Paris, Hopital Saint Louis ( Site 2107) | Paris | |
| France | C.H. Lyon Sud ( Site 2102) | Pierre Benite | Rhone |
| France | Institut Claudius Regaud ( Site 2105) | Toulouse cedex 9 | Haute-Garonne |
| France | Gustave Roussy ( Site 2101) | Villejuif | Ile-de-France |
| Greece | General Hospital of Athens "Laiko"-First Department of Internal Medicine ( Site 2212) | Athens | Attiki |
| Greece | European Interbalkan Medical Center-Oncology Department ( Site 2211) | Thessaloniki | |
| Hungary | Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ ( Site 2221) | Szeged | Csongrad |
| Israel | HaEmek Medical Center ( Site 2703) | Afula | |
| Israel | Rambam Health Care Campus-Oncology ( Site 2704) | Haifa | |
| Israel | Hadassah Ein Karem Jerusalem ( Site 2702) | Jerusalem | |
| Israel | Rabin Medical Center-Oncology ( Site 2705) | Petah-Tikva | |
| Israel | Chaim Sheba Medical Center ( Site 2701) | Ramat Gan | |
| Italy | Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 2399) | Milano | |
| Italy | Istituto Europeo di Oncologia ( Site 2301) | Milano | |
| Italy | Istituto Nazionale Tumori Fondazione Pascale ( Site 2302) | Napoli | |
| Italy | Istituto Oncologico Veneto IRCCS ( Site 2355) | Padova | |
| Italy | Policlinico Le Scotte - A.O. Senese ( Site 2377) | Siena | |
| Poland | Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 2231) | Gdansk | Pomorskie |
| Poland | Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie ( | Warszawa | Mazowieckie |
| South Africa | Cape Town Oncology Trials ( Site 2864) | Cape Town | Western Cape |
| South Africa | CANCERCARE LANGENHOVEN DRIVE ONCOLOGY CENTRE ( Site 2865) | Port Elizabeth | Eastern Cape |
| South Africa | LIFE GROENKLOOF-Mary Potter Cancer Centre ( Site 2861) | Pretoria | Gauteng |
| South Africa | Sandton Oncology Medical Group (Pty) Ltd-Research ( Site 2863) | Sandton | Gauteng |
| South Africa | Steve Biko Academic Hospital-Medical Oncology ( Site 2862) | Tshwane | Gauteng |
| Spain | HOSPITAL CLÍNIC DE BARCELONA-ICHMO- Clinic Institut of Haematological and Oncological diseases ( Sit | Barcelona | Cataluna |
| Spain | Hospital Universitario Ramón y Cajal ( Site 2802) | Madrid | Madrid, Comunidad De |
| Switzerland | Hôpitaux Universitaires de Genève (HUG)-Oncology ( Site 2603) | Genève | Geneve |
| Switzerland | CHUV Centre Hospitalier Universitaire Vaudois ( Site 2602) | Lausanne | Vaud |
| Switzerland | Universitaetsspital Zuerich ( Site 2601) | Zuerich Flughafen | Zurich |
| United States | University of Colorado, Anschutz Cancer Pavilion ( Site 2012) | Aurora | Colorado |
| United States | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 2022) | Baltimore | Maryland |
| United States | Martha Morehouse Tower ( Site 2020) | Columbus | Ohio |
| United States | Duke Cancer Institute ( Site 2005) | Durham | North Carolina |
| United States | Inova Schar Cancer Institute ( Site 2011) | Fairfax | Virginia |
| United States | University of Florida College of Medicine-UF Health Cancer Center/Clinical Trials Office ( Site 2026 | Gainesville | Florida |
| United States | West Cancer Center - East Campus ( Site 2014) | Germantown | Tennessee |
| United States | The Angeles Clinic and Research Institute ( Site 2009) | Los Angeles | California |
| United States | UCLA Hematology & Oncology ( Site 2004) | Los Angeles | California |
| United States | NYU Clinical Cancer Center ( Site 2002) | New York | New York |
| United States | University of Pennsylvania Abramson Cancer Center ( Site 2008) | Philadelphia | Pennsylvania |
| United States | Oregon Health & Science University ( Site 2013) | Portland | Oregon |
| United States | Mays Cancer Center ( Site 2025) | San Antonio | Texas |
| United States | Providence Saint John's Health Center ( Site 2010) | Santa Monica | California |
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme LLC |
United States, Argentina, Australia, Chile, Colombia, France, Greece, Hungary, Israel, Italy, Poland, South Africa, Spain, Switzerland,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Percentage of participants who experience a dose-limiting toxicity (DLT): Safety lead-in phase | The percentage of participants who experience 1 or more protocol-defined DLTs during the safety lead-in period will be reported. | Up to ~3 weeks | |
| Primary | Percentage of participants who experience an adverse event (AE): Safety lead-in | 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 percentage of participants who experience an AE during the safety lead-in period will be reported. | Up to ~3 weeks | |
| Primary | Percentage of participants who discontinue study treatment due to an AE: Safety lead-in | 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 percentage of participants who discontinue study treatment due to an AE during the safety lead-in will be reported. | Up to ~3 weeks | |
| Primary | Percentage of participants who experience 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 percentage of participants who experience an AE will be reported. | Up to ~28 months | |
| Primary | Percentage of participants who discontinue study treatment due to an 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 percentage of participants who discontinue study treatment due to an AE will be reported. | Up to ~24 months | |
| Primary | Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) | ORR is defined as the percentage of participants in the analysis population who have 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, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by blinded independent central review (BICR). RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. | Up to ~30 months | |
| Secondary | Duration of Response (DOR) per RECIST 1.1 | For participants in the analysis population who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters), DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 as assessed by BICR. RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. | Up to ~30 months |
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