A Study of Coformulated Favezelimab/Pembrolizumab (MK-4280A) Versus Standard of Care in Subjects With Previously Treated Metastatic PD-L1 Positive Colorectal Cancer (MK-4280A-007)

A Phase 3 Study of MK-4280A (Coformulated Favezelimab [MK-4280] Plus Pembrolizumab [MK-3475]) Versus Standard of Care in Previously Treated Metastatic PD-L1 Positive Colorectal Cancer (KEYFORM-007)

The purpose of this study is to assess the safety and efficacy of coformulated favezelimab/pembrolizumab (MK-4280A) in participants with metastatic colorectal cancer. The study will also compare MK-4280A with the standard of care treatment of regorafenib and TAS-102 (trifluridine and tipiracil).

The primary study hypothesis is that coformulated favezelimab/pembrolizumab (MK-4280A) is superior to standard of care with respect to overall survival.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Biological: favezelimab/pembrolizumab; Drug: regorafenib; Drug: TAS-102

• Study Type: Interventional
• Enrollment (Estimated): 432
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital ( Site 0057)
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women s Hospital ( Site 0058)
  • South Australia
    • Woodville South, South Australia, Australia, 5011
      • Queen Elizabeth Hospital ( Site 0050)
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Frankston Hospital ( Site 0056)
    • St Albans, Victoria, Australia, 3021
      • Western Health-Sunshine & Footscray Hospitals ( Site 0052)
  • Western Australia
    • Perth, Western Australia, Australia, 6008
      • St John of God Subiaco Hospital ( Site 0051)
• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Regional Cancer Program - London HSC ( Site 0154)
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital ( Site 0151)
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0155)
• Chile
  • Araucania
    • Temuco, Araucania, Chile, 4800827
      • Centro Investigacion Cancer James Lind ( Site 0204)
  • Coquimbo
    • La Serena, Coquimbo, Chile, 1720430
      • IC La Serena Research ( Site 0202)
  • Los Lagos
    • Puerto Montt, Los Lagos, Chile, 5500656
      • Clinica Puerto Montt ( Site 0211)
  • Region M. De Santiago
    • Santiago, Region M. De Santiago, Chile, 7500921
      • Fundacion Arturo Lopez Perez FALP ( Site 0208)
    • Santiago, Region M. De Santiago, Chile, 7510032
      • Oncovida ( Site 0209)
    • Santiago, Region M. De Santiago, Chile, 8241479
      • Clínica Vespucio ( Site 0205)
    • Santiago, Region M. De Santiago, Chile, 8330032
      • Pontificia Universidad Catolica de Chile ( Site 0206)
    • Santiago, Region M. De Santiago, Chile, 8420383
      • Bradfordhill ( Site 0200)
• China
  • Anhui
    • Hefei, Anhui, China, 230601
      • The Second Affiliated Hospital of Anhui Medical University ( Site 1179)
  • Chongqing
    • Chongqing, Chongqing, China, 400030
      • Chongqing Cancer Hospital ( Site 1151)
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Province Cancer Hospital ( Site 1178)
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-Sen University Cancer Center ( Site 1150)
    • Guangzhou, Guangdong, China, 510515
      • Southern Medical University Nanfang Hospital ( Site 1154)
    • Guangzhou, Guangdong, China, 510655
      • The Sixth Affiliated Hospital of Sun Yat-sen University ( Site 1159)
  • Guangxi
    • Nanning, Guangxi, China, 531021
      • Guangxi Medical University Affiliated Tumor Hospital ( Site 1158)
  • Hainan
    • Haikou, Hainan, China, 570311
      • Hainan General Hospital ( Site 1177)
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Wuhan Union Hospital Cancer Center ( Site 1162)
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital ( Site 1152)
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital Central South University ( Site 1171)
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital ( Site 1174)
    • Changsha, Hunan, China, 410013
      • The Third Xiangya Hospital of Central South University ( Site 1175)
  • Jiangsu
    • Changzhou, Jiangsu, China, 213000
      • Changzhou Cancer Hospital-Department of Oncology ( Site 1183)
    • Wuxi City, Jiangsu, China, 214122
      • Affiliated Hospital of Jiangnan University(Wuxi Fourth People's Hospital ) ( Site 1185)
  • Jilin
    • Changchun, Jilin, China, 130012
      • Jilin Cancer Hospital ( Site 1163)
  • Shandong
    • Jinan, Shandong, China, 250000
      • Jinan Central Hospital ( Site 1167)
  • Shanghai
    • Shangai, Shanghai, China, 201321
      • Fudan University Shanghai Cancer Center ( Site 1176)
    • Shanghai, Shanghai, China, 200072
      • Shanghai Tenth People's Hospital ( Site 1170)
  • Sichuan
    • Chengdu, Sichuan, China, 332001
      • West China Hospital Sichuan University ( Site 1172)
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital ( Site 1161)
  • Yunnan
    • Kunming, Yunnan, China, 650106
      • Yunnan Province Cancer Hospital-Colorectal surgery ( Site 1169)
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310005
      • Zhejiang Cancer Hospital ( Site 1180)
    • Hangzhou, Zhejiang, China, 310018
      • Sir Run Run Shaw Hospital-Medical Oncology ( Site 1173)
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove ( Site 1207)
  • Olomouc, Czechia, 779 00
    • Fakultni nemocnice Olomouc ( Site 1204)
  • Praha 10, Czechia, 100 34
    • Fakultni nemocnice Kralovske Vinohrady ( Site 1208)
  • Praha 4, Czechia, 140 59
    • Fakultni Thomayerova nemocnice ( Site 1205)
  • Praha 8, Czechia, 180 81
    • Fakultni nemocnice Na Bulovce ( Site 1202)
  • Brno-mesto
    • Brno, Brno-mesto, Czechia, 656 53
      • Masarykuv onkologicky ustav ( Site 1203)
  • Praha, Hlavni Mesto
    • Praha, Praha, Hlavni Mesto, Czechia, 150 06
      • Fakultni nemocnice v Motole ( Site 1201)
• France
  • Paris, France, 75015
    • Hopital Europeen Georges Pompidou ( Site 0300)
  • Gironde
    • Pessac, Gironde, France, 33604
      • CHU Bordeaux Haut-Leveque ( Site 0305)
  • Pays-de-la-Loire
    • Nantes, Pays-de-la-Loire, France, 44093
      • CHU Hotel Dieu Nantes ( Site 0303)
  • Vaucluse
    • Avignon, Vaucluse, France, 84000
      • Institut du Cancer Avignon-Provence ( Site 0306)
  • Vienne
    • Poitiers, Vienne, France, 86021
      • CHU Poitiers ( Site 0304)
• Germany
  • Hamburg, Germany, 22087
    • Katholisches Marienkrankenhaus gGmbH ( Site 1257)
  • Bayern
    • Muenchen, Bayern, Germany, 81377
      • LMU Klinikum Grosshadern der Universitaet Muenchen ( Site 1253)
  • Hessen
    • Marburg, Hessen, Germany, 35043
      • Philipps-Universitaet Marburg. ( Site 1252)
  • Niedersachsen
    • Wolfsburg, Niedersachsen, Germany, 38440
      • Klinikum Wolfsburg ( Site 1256)
  • Nordrhein-Westfalen
    • Bonn, Nordrhein-Westfalen, Germany, 53113
      • Johanniter Krankenhaus Bonn ( Site 1254)
    • Moenchengladbach, Nordrhein-Westfalen, Germany, 41063
      • Kliniken Maria Hilf GmbH ( Site 1255)
  • Sachsen-Anhalt
    • Halle (Saale), Sachsen-Anhalt, Germany, 06120
      • Universitätsklinikum Halle ( Site 1251)
• Israel
  • Ashdod, Israel, 7747629
    • Assuta Ashdod Public ( Site 0507)
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus-Oncology Division ( Site 0500)
  • Haifa, Israel, 3339419
    • Bnei Zion Medical Center ( Site 0506)
  • Jerusalem, Israel, 9112001
    • Hadassa Ein Karem Medical Center ( Site 0504)
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center ( Site 0503)
  • Ramat Gan, Israel, 5262000
    • Chaim Sheba Medical Center ( Site 0501)
  • Tel Aviv, Israel, 6423906
    • Sourasky Medical Center ( Site 0502)
• Italy
  • Catania, Italy, 95122
    • A.O. di Rilievo Nazionale e di alta Specializzazione Garibaldi ( Site 0553)
  • Milano, Italy, 20162
    • ASST Grande Ospedale Metropolitano Niguarda ( Site 0550)
  • Napoli, Italy, 80131
    • Universita degli Studi della Campania Luigi Vanvitelli-UOC Oncoematologia ( Site 0556)
  • Abruzzo
    • Roma, Abruzzo, Italy, 00168
      • Policlinico Gemelli di Roma ( Site 0552)
  • Foggia
    • San Giovanni Rotondo, Foggia, Italy, 71013
      • IRCCS Casa Sollievo della Sofferenza ( Site 0554)
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Istituto Clinico Humanitas - Cancer Center ( Site 0555)
• Japan
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center ( Site 0609)
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital ( Site 0601)
  • Tokyo, Japan, 135-8550
    • Japanese Foundation for Cancer Research ( Site 0602)
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East ( Site 0600)
  • Kagawa
    • Kita-gun, Kagawa, Japan, 761-0793
      • Kagawa University Hospital ( Site 0608)
  • Osaka
    • Osakasayama, Osaka, Japan, 5898511
      • Kindai University Hospital ( Site 0607)
  • Saitama
    • Kitaadachi-gun, Saitama, Japan, 362-0806
      • Saitama Prefectural Cancer Center ( Site 0603)
  • Shizuoka
    • Sunto-gun,, Shizuoka, Japan, 411-8777
      • Shizuoka Cancer Center ( Site 0605)
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital ( Site 0653)
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital ( Site 0652)
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center ( Site 0651)
  • Seoul
    • Songpagu, Seoul, Korea, Republic of, 05505
      • Asan Medical Center ( Site 0650)
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • University Malaya Medical Centre ( Site 1301)
  • Kuala Lumpur
    • Bangsar, Kuala Lumpur, Malaysia, 59100
      • Pantai Hospital Kuala Lumpur ( Site 1303)
  • Selangor
    • Petaling Jaya, Selangor, Malaysia, 46050
      • Beacon Hospital Sdn Bhd ( Site 1305)
  • Wilayah Persekutuan Putrajaya
    • Putrajaya, Wilayah Persekutuan Putrajaya, Malaysia, 62250
      • Institut Kanser Negara - National Cancer Institute ( Site 1302)
• Norway
  • Oslo, Norway, 0450
    • Oslo Universitetssykehus HF. Ulleval ( Site 1351)
  • Akershus
    • Loerenskog, Akershus, Norway, 1478
      • Akershus universitetssykehus ( Site 1352)
  • Sor-Trondelag
    • Trondheim, Sor-Trondelag, Norway, 7030
      • St Olavs Hospital ( Site 1354)
  • Troms
    • Tromsoe, Troms, Norway, 9019
      • Universitetssykehuset i Nord Norge. ( Site 1355)
  • Vestfold
    • Bergen, Vestfold, Norway, 5053
      • Helse Bergen HF - Haukeland univeritetssykehus ( Site 1353)
• Russian Federation
  • Sankt-Peterburg, Russian Federation, 188663
    • SHBI "Leningrad Regional Clinical Oncology Dispensary n.a. L.D. Roman"-Clinical Trials Department (
  • Baskortostan, Respublika
    • Ufa, Baskortostan, Respublika, Russian Federation, 450054
      • Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 0871)
  • Kirovskaya Oblast
    • Kirov, Kirovskaya Oblast, Russian Federation, 105094
      • SRBHI of Kirov Region Center of Oncology and medical radiology ( Site 0854)
  • Moskva
    • Moscow, Moskva, Russian Federation, 105094
      • Main Military Clinical Hospital n.a. N.N.Burdenko ( Site 0870)
    • Moscow, Moskva, Russian Federation, 115682
      • FSBI-FRCC of Special Types Med. Care and Technologies FMBA of Russia ( Site 0851)
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 197706
      • City Hospital #40 ( Site 0853)
    • Saint-Petersburg, Sankt-Peterburg, Russian Federation, 197758
      • Clinical Research Center of specialized types medical care-Oncology ( Site 0860)
  • Tomskaya Oblast
    • Tomsk, Tomskaya Oblast, Russian Federation, 634045
      • Tomsk National Research Medical Center of Russian Academy of Sciences ( Site 0872)
  • Yaroslavskaya Oblast
    • Yaroslavl, Yaroslavskaya Oblast, Russian Federation, 150054
      • Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 0850)
• South Africa
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6045
      • Cancer Care Langenhoven Drive Oncology Centre ( Site 1504)
  • Gauteng
    • Sandton, Gauteng, South Africa, 2196
      • Sandton Oncology Medical Group PTY LTD ( Site 1501)
  • Western Cape
    • Kraaifontein, Western Cape, South Africa, 7570
      • Cape Town Oncology Trials Pty Ltd ( Site 1506)
    • Rondebosch, Western Cape, South Africa, 7700
      • Cancercare Rondebosch Oncology ( Site 1509)
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d Hebron ( Site 0900)
  • Barcelona, Spain, 08041
    • Hospital Sant Pau i la Santa Creu ( Site 0905)
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos ( Site 0902)
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre ( Site 0901)
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena ( Site 0906)
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital ( Site 0953)
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital ( Site 0955)
  • Taipei, Taiwan, 10048
    • National Taiwan University Hospital ( Site 0950)
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital ( Site 0951)
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation. Linkou ( Site 0952)
  • Changhua
    • Kaohsiung, Changhua, Taiwan, 833
      • Chang Gung Medical Foundation - Kaohsiung ( Site 0956)
• Turkey
  • Adana, Turkey, 01120
    • Baskent Universitesi Dr. Turgut Noyan Uygulama ve Arastirma Merkezi ( Site 1007)
  • Adana, Turkey, 01130
    • Acibadem Adana Hastanesi ( Site 1008)
  • Ankara, Turkey, 06010
    • Gulhane Egitim ve Arastirma Hastanesi ( Site 1009)
  • Ankara, Turkey, 06230
    • Hacettepe Universitesi Tip Fakultesi ( Site 1003)
  • Ankara, Turkey, 06800
    • Ankara Sehir Hastanesi ( Site 1005)
  • Antalya, Turkey, 07100
    • Antalya Egitim ve Arastirma Hastanesi ( Site 1010)
  • Istanbul, Turkey, 34722
    • Goztepe Prof.Dr. Suleyman Yalcin Sehir Hastanesi ( Site 1002)
  • Izmir, Turkey, 35100
    • Ege Universitesi Tip Fakultesi Hastanesi ( Site 1006)
• Ukraine
  • Dnipropetrovska Oblast
    • Dnipro, Dnipropetrovska Oblast, Ukraine, 49102
      • Municipal Non-Profit Enterprise City Clinical Hospital 4 of Dnipro City Council ( Site 1657)
  • Ivano-Frankivska Oblast
    • Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine, 76018
      • MI Precarpathian Clinical Oncology Center ( Site 1654)
  • Kirovohradska Oblast
    • Kropyvnytskyi, Kirovohradska Oblast, Ukraine, 25011
      • Ukrainian Center of Tomotherapy ( Site 1658)
  • Odeska Oblast
    • Odesa, Odeska Oblast, Ukraine, 65025
      • Odessa Regional Clinical Hospital ( Site 1664)
• United Kingdom
  • Cardiff, United Kingdom
    • Velindre Cancer Centre ( Site 1058)
  • Leeds, United Kingdom, LS9 7TF
    • Leeds Teaching Hospitals NHS Trust ( Site 1050)
  • Camden
    • London, Camden, United Kingdom, WC1E 6AG
      • University College London Hospitals NHS Foundation Trust ( Site 1056)
  • London, City Of
    • London, London, City Of, United Kingdom, SW3 6JJ
      • Royal Marsden NHS Foundation Trust ( Site 1064)
    • London, London, City Of, United Kingdom, W12 0HS
      • Imperial College Healthcare NHS Trust - Hammersmith Hospital ( Site 1052)
    • Sutton, London, City Of, United Kingdom, SM25PT
      • Royal Marsden NHS Trust ( Site 1063)
  • Warwickshire
    • Coventry, Warwickshire, United Kingdom, CV2 2DX
      • University Hospital Coventry & Warwickshire ( Site 1062)
• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital ( Site 1148)
    • Washington, District of Columbia, United States, 20016
      • Sibley Memorial Hospital ( Site 1143)
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital-Research ( Site 1118)
  • Kentucky
    • Louisville, Kentucky, United States, 40217
      • Norton Cancer Institute ( Site 1139)
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey ( Site 1105)
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center ( Site 1703)
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University ( Site 1141)
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • MUSC Hollings Cancer Center ( Site 1715)
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • The West Clinic, PLLC dba West Cancer Center ( Site 1149)
  • Texas
    • Dallas, Texas, United States, 75390-9063
      • UT Southwestern Medical Center ( Site 1709)
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center ( Site 1707)
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute ( Site 1130)
    • Richmond, Virginia, United States, 23219
      • VCU Health Adult Outpatient Pavillion ( Site 1712)
    • Roanoke, Virginia, United States, 24014
      • Blue Ridge Cancer Care ( Site 1718)
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance ( Site 1107)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has a histologically confirmed colorectal adenocarcinoma that is metastatic and unresectable.
• Has measurable disease per RECIST 1.1 as assessed by the local site investigator.
• Has been previously treated for the disease and radiographically progressed on or after or could not tolerate standard treatment.
• Submits an archival (≤ 5 years) or newly obtained tumor tissue sample or newly obtained tumor tissue sample that has not been previously irradiated.
• Has an Eastern Cooperative Oncology Group Performance Score (ECOG PS) of 0 to 1 within 10 days prior to first dose of study intervention.
• Has a life expectancy of at least 3 months, based on the investigator assessment.
• Has the ability to swallow and retain oral medication and not have any clinically significant gastrointestinal abnormalities that might alter absorption.
• Has adequate organ function.

Exclusion Criteria:

• Has previously been found to have deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) tumor status.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis or leptomeningeal disease.
• Has a history of acute or chronic pancreatitis.
• Has neuromuscular disorders associated with an elevated creatine kinase (eg, inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
• Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
• Has urine protein greater than or equal to 1g/24h.
• A woman of childbearing potential who has a positive urine/serum pregnancy test within 24/72 hours prior to the first dose of study intervention.
• Has received prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed death ligand 1 (PD-L1), or anti-programmed cell death ligand 2 (PD-L2), anti-lymphocyte activation gene 3 (LAG-3) antibody, with a tyrosine kinase inhibitor (TKI; eg, lenvatinib) other than rapidly accelerated fibrosarcoma (RAF) inhibitors (binimetinib is permitted if combined with a RAF inhibitor), or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4, OX-40, cluster of differentiation [CD] 137).
• Has previously received regorafenib or TAS-102.
• Has received prior systemic anticancer therapy including investigational agents within 28 days before randomization.
• Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has an active autoimmune disease that has required systemic treatment in past 2 years.
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy (eg, tuberculosis, known viral or bacterial infections, etc.).
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has known history of Hepatitis B or known active Hepatitis C virus infection.
• 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.
• Has had an allogenic tissue/solid organ transplant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Favezelimab/Pembrolizumab; Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) intravenously (IV) on Day 1, then every 3 weeks (Q3W), for up to 35 infusions.	Biological: favezelimab/pembrolizumab; Coformulated favezelimab/pembrolizumab (800 mg/200 mg), IV infusion; Other Names: MK-4280A
Active Comparator: Standard of Care (Regorafenib or TAS-102); At the Investigator's choice, participants will receive 160 mg regorafenib orally daily on Days 1-12 of each 28-day cycle or 35 mg/m^2 TAS-102 orally twice daily on Days 1-5 and Days 8-12 of each 28-day cycle.	Drug: regorafenib; Oral; Other Names: STIVARGA®; REGONIX®; Drug: TAS-102; Oral; Other Names: LONSURF®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to approximately 26 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) according per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR)	PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 by BICR or death due to any cause, whichever occurs first.	Up to approximately 19 months
Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR	The ORR is defined as the percentage of participants who achieve a confirmed complete response (CR) or partial response (PR) per RECIST 1.1 as assessed by BICR.	Up to approximately 19 months
Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR	For participants who demonstrate confirmed CR or PR, duration of response 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 19 months
Number of Participants Who Experience 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.	Up to approximately 27 months
Number 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 number of participants who discontinue study treatment due to an AE will be reported.	Up to approximately 24 months
Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score	The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score will be presented. A higher score indicates a better outcome.	Baseline and up to approximately 25 months
Change from Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score	The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning (Items 1-5) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores meant a better level of function.	Baseline and up to approximately 25 months
Change from Baseline in EORTC QLQ-C30 Appetite Loss (Item 13) Score	The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire, including a single-item scale score for appetite loss (QLQ-C30 Item 13). For this item, individual responses to the question "Have you lacked appetite?" are given on a 4-point scale (1=Not at all; 4=Very much). Scores are transformed to a range from 0-100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-C30 appetite loss (Item 13) scale score will be presented.	Baseline and up to approximately 25 months
Change from Baseline in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score	The EORTC QLQ-CR29 is a health-related quality-of life (QoL) questionnaire specific for colorectal cancer, including a single-item scale score for bloating (QLQ-CR29 Item 37). For this item, individual responses to the question "Did you have a bloated feeling in your abdomen?" are given on a 4-point scale (1=Not at all; 4=Very much). Scores are transformed to a range from 0-100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-CR29 bloating (Item 37) scale score will be presented.	Baseline and up to approximately 25 months
Time to Deterioration (TTD) in EORTC QLQ-C30 GHS (Item 29) and QoL (Item 30) Combined Score	TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (decrease) from baseline in GHS (EORTC QLQ-C30 Item 29) & QoL combined score (EORTC QLQ-C30 Item 30). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in GHS and QoL combined score, will be presented. A longer TTD indicates a better outcome.	Baseline and up to approximately 25 months
TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score	TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (decrease) from baseline in physical functioning score (EORTC QLQ-C30 Items 1-5). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in GHS and QoL combined score, will be presented. A longer TTD indicates a better outcome.	Baseline and up to approximately 25 months
TTD in in EORTC QLQ-C30 Appetite Loss (Item 13) Score	TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (decrease) from baseline in appetite loss score (EORTC QLQ-C30 Item 13). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in physical functioning score, will be presented. A longer TTD indicates a better outcome.	Baseline and up to approximately 25 months
TTD in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score	TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (decrease) from baseline in bloating score (QLQ-CR29 Item 37). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in appetite loss score, will be presented. A longer TTD indicates a better outcome.	Baseline and up to approximately 25 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2021
• Primary Completion (Estimated): August 15, 2024
• Study Completion (Estimated): November 11, 2025

Study Registration Dates

• First Submitted: September 29, 2021
• First Submitted That Met QC Criteria: September 29, 2021
• First Posted (Actual): October 1, 2021

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Programmed Cell Death-1 (PD1, PD-1),; Programmed Cell Death Receptor Ligand 1 (PDL1, PD-L1); Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: 4280A-007; jRCT2031210482 (Registry Identifier: jRCT(Japan Registry of Clinical Trials)); MK-4280A-007 (Other Identifier: Merck); 2021-001309-60 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No