Evaluation of Co-formulated Pembrolizumab/Quavonlimab (MK-1308A) Versus Other Treatments in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Cancer (CRC) (MK-1308A-008)
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the efficacy and safety of co-formulated pembrolizumab/quavonlimab versus other treatments in participants with MSI-H or dMMR Metastatic Stage IV Colorectal Cancer.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Active Comparator: Pembrolizumab Participants receive pembrolizumab 400 mg intravenously (IV) every 6 weeks (Q6W) for up to approximately 2 years. |
Biological: Pembrolizumab
400 mg or 200 mg pembrolizumab administered via IV infusion.
Other Names:
|
Experimental: Pembrolizumab/Quavonlimab Participants receive co-formulated pembrolizumab/quavonlimab (400 mg/25 mg) Q6W for up to approximately 2 years. |
Biological: Pembrolizumab/Quavonlimab
Co-formulated pembrolizumab/quavonlimab (400 mg/25 mg) fixed-dose combination (FDC) administered via IV infusion.
Other Names:
|
Experimental: Pembrolizumab/Favezelimab Participants receive co-formulated pembrolizumab/favezelimab (200 mg/800 mg) every 3 weeks (Q3W) for up to approximately 2 years. |
Biological: Pembrolizumab/Favezelimab
Co-formulated pembrolizumab/favezelimab (200 mg/800 mg) FDC administered via IV infusion
Other Names:
|
Experimental: Pembrolizumab/Vibostolimab Participants receive co-formulated pembrolizumab/vibostolimab (200 mg/200 mg) Q3W for up to approximately 2 years. |
Biological: Pembrolizumab/Vibostolimab
Co-formulated pembrolizumab/vibostolimab (200 mg/200 mg) FDC administered via IV infusion
Other Names:
|
Experimental: Pembrolizumab Plus MK-4830 Participants receive pembrolizumab 200 mg plus MK-4830 800 mg Q3W for up to approximately 2 years. |
Biological: Pembrolizumab
400 mg or 200 mg pembrolizumab administered via IV infusion.
Other Names:
Biological: MK-4830
800 mg MK-4830 administered via IV infusion
|
Outcome Measures
Primary Outcome Measures
- Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR) [Up to approximately 39 months]
ORR is defined as the percentage of participants who have a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR as assessed by BICR will be presented.
Secondary Outcome Measures
- Duration of Response (DOR) per RECIST 1.1 as assessed by BICR [Up to approximately 39 months]
DOR is defined as the time from the first documented evidence of a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 until Progressive Disease (PD) or death due to any cause, whichever occurs first, in participants demonstrating a CR or PR. 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 BICR will be presented.
- Progression-Free Survival (PFS) per RECIST 1.1 as assessed by BICR [Up to approximately 39 months]
PFS is defined as the time from randomization (or first dose) to the first documented PD per RECIST 1.1 or death from any cause, whichever occurs first. 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. PFS as assessed by BICR will be presented.
- PFS per RECIST 1.1 as assessed by Investigator [Up to approximately 39 months]
PFS is defined as the time from randomization (or first dose) to the first documented PD per RECIST 1.1 or death from any cause, whichever occurs first. 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. PFS as assessed by investigator will be presented.
- ORR per RECIST 1.1 as assessed by Investigator [Up to approximately 39 months]
ORR is defined as the percentage of participants who have a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR as assessed by investigator will be presented.
- DOR per RECIST 1.1 as assessed by Investigator [Up to approximately 39 months]
DOR is defined as the time from the first documented evidence of a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 until PD or death due to any cause, whichever occurs first, in participants demonstrating a CR or PR. 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 investigator will be presented.
- Overall Survival (OS) [Up to approximately 39 months]
OS is defined as the time from randomization (or first dose) to death due to any cause. OS will be presented.
- Number of Participants Who Experienced an Adverse Event (AE) [Up to approximately 27 months]
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study intervention. The number of participants with an AE will be presented.
- Number of Participants Discontinuing Study Treatment Due to an AE [Up to approximately 24 months]
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study intervention. The number of participants that discontinue study treatment due to an AE will be presented.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Has a histologically confirmed diagnosis of Stage IV CRC adenocarcinoma (as defined by American Joint Committee on Cancer [AJCC] version 8)
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Has locally confirmed dMMR/MSI-H
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Has a life expectancy of at least 3 months
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Female participants are eligible to participate if not pregnant or breastfeeding, and not a woman of childbearing potential (WOCBP), or if a WOCBP then uses a contraceptive method that is highly effective or is abstinent on a long-term and persistent basis, during the intervention period and for at least 120 days after the last dose of study intervention
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Has measurable disease per RECIST 1.1 as assessed by the site and verified by BICR
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Submit an archival or newly obtained tumor tissue sample that has not been previously irradiated; formalin-fixed, paraffin embedded (FFPE) blocks are preferred to slides.
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Has adequate organ function
Cohort A:
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Has been previously treated for their disease and radiographically progressed per RECIST 1.1 on or after or could not tolerate standard treatment, which must include all of the following agents if approved and locally available in the country where the participant is randomized:
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Fluoropyrimidine, irinotecan and oxaliplatin (capecitabine is acceptable as equivalent to fluorouracil in prior therapy)
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With or without an anti-vascular endothelial growth factor (VEGF) monoclonal antibody (e.g., bevacizumab)
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At least one of the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab or panitumumab) for rat sarcoma viral oncogene homolog (RAS) wild-type participants with left-sided tumors. Prior EGFR therapy is optional for patients with right sided RAS Wild-type (WT) tumors.
Cohort B:
- Has untreated Stage IV dMMR/MSI-H CRC with no prior chemotherapy or immunotherapy for this disease
Exclusion Criteria:
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Has received prior therapy with an agent directed to another stimulatory or coinhibitory T-cell receptor
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Has received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention
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Has not recovered adequately from a surgery procedure, and/or has any complications from a prior surgery before starting study intervention
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Has received prior radiotherapy within 2 weeks of start of study intervention
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Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
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Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention
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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 the first dose of study medication
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Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
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Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
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Has severe hypersensitivity (≥Grade 3) to pembrolizumab, quavonlimab, favezelimab, vibostolimab, MK-4830, and/or any of their excipients
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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)
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Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
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Has a history of acute or chronic pancreatitis
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Has neuromuscular disorders associated with an elevated creatine kinase
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Has urine protein ≥1 gram/24 hours
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Has an active infection requiring systemic therapy (e.g., tuberculosis, known viral or bacterial infections, etc.)
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Has a known history of Human Immunodeficiency Virus (HIV) infection
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Has known active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] positive and/or detectable Hepatitis B Virus [HBV] deoxyribonucleic acid [DNA]) or active Hepatitis C virus (defined as HCV ribonucleic acid [RNA] [qualitative] is detected or anti-HCV antibody positive) infection
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Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study intervention administration, or New York Heart Association Class III or IV congestive heart failure. Medically controlled arrhythmia stable on medication is permitted.
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Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks before randomization/allocation
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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
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Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
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Has had an allogenic tissue/solid organ transplant
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Mid Florida Cancer Center ( Site 1519) | Orange City | Florida | United States | 32763 |
2 | University Cancer & Blood Center, LLC ( Site 1521) | Athens | Georgia | United States | 30607 |
3 | University of Chicago Medical Center-Medicine - Section of Hematology/Oncology - Gastrointestinal P | Chicago | Illinois | United States | 60637 |
4 | UPMC Hillman Cancer Center ( Site 1516) | Pittsburgh | Pennsylvania | United States | 15232 |
5 | Vanderbilt University Medical Center-Vanderbilt-Ingram Cancer Center ( Site 1509) | Nashville | Tennessee | United States | 37232 |
6 | Baylor Scott & White Medical Center - Temple-Division of Hematology/Oncology ( Site 1549) | Temple | Texas | United States | 76508 |
7 | Northwest Medical Specialties, PLLC ( Site 1546) | Tacoma | Washington | United States | 98405 |
8 | UZ Brussel ( Site 0105) | Brussels | Bruxelles-Capitale, Region De | Belgium | 1090 |
9 | Université Catholique de Louvain-Namur - Centre Hospitalier -Oncology ( Site 0102) | Yvoir | Namur | Belgium | 5530 |
10 | UZ Leuven ( Site 0101) | Leuven | Vlaams-Brabant | Belgium | 3000 |
11 | The Moncton Hospital-Oncology ( Site 0307) | Moncton | New Brunswick | Canada | E1C 6Z8 |
12 | McGill University Health Centre-CIM - Oncology ( Site 0306) | Montréal | Quebec | Canada | H4A 3J1 |
13 | Assistance Publique Hôpitaux de Marseille - Hôpital de la Ti-Service d'Hepato-Gastro-Enterologie et | Marseille | Bouches-du-Rhone | France | 13385 |
14 | Centre Georges François Leclerc ( Site 0506) | Dijon | Cote-d Or | France | 21079 |
15 | CHU Rangueil-Digestive oncology department ( Site 0502) | Toulouse | Haute-Garonne | France | 31059 |
16 | Hopital Claude Huriez - CHU de Lille ( Site 0510) | Lille | Nord | France | 59037 |
17 | Centre Hospitalier Universitaire de Poitiers ( Site 0511) | Poitiers | Vienne | France | 86021 |
18 | Hôpital Saint Antoine-Oncologie médicale ( Site 0508) | Paris | France | 75571 | |
19 | Universitaetsklinikum Carl Gustav Carus Dresden-Medical Dept I - Medical Oncology ( Site 0601) | Dresden | Sachsen | Germany | 01307 |
20 | Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0604) | Berlin | Germany | 10117 | |
21 | Asklepios Altona-Oncology ( Site 0602) | Hamburg | Germany | 22763 | |
22 | Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 0802) | Milan | Lombardia | Italy | 20133 |
23 | Istituto Oncologico Veneto IRCCS ( Site 0804) | Padova | Veneto | Italy | 35128 |
24 | Istituto Nazionale Tumori IRCCS Fondazione Pascale-Department of Abdominal Oncology ( Site 0803) | Napoli | Italy | 80131 | |
25 | Kyungpook National University Chilgok Hospital-Hematology/oncology ( Site 1103) | Daegu | Taegu-Kwangyokshi | Korea, Republic of | 41404 |
26 | Korea University Anam Hospital ( Site 1107) | Seoul | Korea, Republic of | 02841 | |
27 | Seoul National University Hospital-Internal Medicine ( Site 1101) | Seoul | Korea, Republic of | 03080 | |
28 | Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1104) | Seoul | Korea, Republic of | 03722 | |
29 | Asan Medical Center-Department of Oncology ( Site 1105) | Seoul | Korea, Republic of | 05505 | |
30 | Samsung Medical Center-Division of Hematology/Oncology ( Site 1102) | Seoul | Korea, Republic of | 06351 | |
31 | The Catholic Univ. of Korea Seoul St. Mary's Hospital-Medical Oncology ( Site 1106) | Seoul | Korea, Republic of | 06591 | |
32 | Powiatowe Centrum Zdrowia ( Site 0911) | Brzeziny | Lodzkie | Poland | 95-060 |
33 | Luxmed Onkologia sp. z o. o. ( Site 0915) | Warszawa | Mazowieckie | Poland | 01-748 |
34 | Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Onkologii i Radioterapii ( Site | Warszawa | Mazowieckie | Poland | 02-034 |
35 | Mrukmed-Mrukmed ( Site 0901) | Rzeszow | Podkarpackie | Poland | 35-021 |
36 | Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0903) | Koszalin | Zachodniopomorskie | Poland | 75-581 |
37 | Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 1001) | Saint Petersburg | Leningradskaya Oblast | Russian Federation | 198255 |
38 | Fed State Budgetary Inst N.N. Blokhin Med Center of Oncology-Clinical Pharmacology and Chemotherapy | Moscow | Moskva | Russian Federation | 115478 |
39 | First Moscow State Medical University I.M. Sechenov-Interhospital Institution Health Management Cl | Moscow | Moskva | Russian Federation | 119991 |
40 | Rostov Cancer Research Institute ( Site 1014) | Rostov on Don | Rostovskaya Oblast | Russian Federation | 344037 |
41 | GBUZ SPb CRPCstmc(o) ( Site 1005) | Sankt- Peterburg | Sankt-Peterburg | Russian Federation | 197758 |
42 | Republican Clinical Oncology Dispensary-Chemotherapy #3 ( Site 1006) | Kazan | Tatarstan, Respublika | Russian Federation | 420029 |
43 | Hospital Universitario Central de Asturias-Medical Oncology ( Site 1203) | Oviedo | Asturias | Spain | 33011 |
44 | Hospital Universitario Marqués de Valdecilla ( Site 1202) | Santander | Cantabria | Spain | 39008 |
45 | Hospital Universitari Vall d'Hebron ( Site 1201) | Barcelona | Spain | 08035 | |
46 | HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 1206) | Madrid | Spain | 28007 | |
47 | Hospital Clinico San Carlos-Oncology Department ( Site 1204) | Madrid | Spain | 28040 | |
48 | Baskent University Dr. Turgut Noyan Research and Training Center ( Site 1303) | Adana | Turkey | 01250 | |
49 | Hacettepe Universitesi-oncology hospital ( Site 1301) | Ankara | Turkey | 06230 | |
50 | Ankara City Hospital-Medical Oncology ( Site 1306) | Ankara | Turkey | 06800 | |
51 | TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1305) | Istanbul | Turkey | 34722 | |
52 | Beatson West of Scotland Cancer Centre-Clinical Trials Unit ( Site 1401) | Glasgow | Glasgow City | United Kingdom | G15 6HG |
53 | UCLH-Cancer Clinical Trials Unit ( Site 1402) | London | London, City Of | United Kingdom | NW1 2PG |
54 | Velindre Cancer Centre-Research and Development ( Site 1415) | Cardiff | United Kingdom | CF14 2TL | |
55 | University Hospital Coventry & Warwickshire ( Site 1406) | Coventry | United Kingdom | CV2 2DX |
Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 1308A-008
- MK-1308A-008
- 2020-005114-18