Neoplasm MalignantPhase 2NCT04976634
Pembrolizumab Plus Lenvatinib in Combination With Belzutifan in Solid Tumors (MK-6482-016)
A Phase 2 study testing Pembrolizumab, Belzutifan and Lenvatinib in people with Neoplasm Malignant, run by Merck Sharp & Dohme LLC at 57 sites in 10 countries.
Trial summary
The purpose of this study is to determine the safety and efficacy of belzutifan in combination with pembrolizumab and lenvatinib in multiple solid tumors including hepatocellular carcinoma (HCC), colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), biliary tract cancer (BTC), endometrial cancer (EC),and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasm Malignant
- What is being tested?
- Pembrolizumab, Belzutifan and Lenvatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 730 participants
- Where
- 57 sitesin 10 countries
- Study dates
- 18 Aug 2021to 22 Mar 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of one of the following advanced (unresectable and/or metastatic) solid tumors, documented by histopathology or cytopathology:
- Hepatocellular carcinoma (HCC)
- Colorectal cancer (CRC) (non-microsatellite instability-high [non-MSI-H]/deficient mismatch repair [dMMR])
- Pancreatic ductal adenocarcinoma (PDAC).
- Biliary tract cancer (BTC) (includes intrahepatic, extrahepatic cholangiocarcinoma [CCA] and gall bladder cancer)
- Endometrial cancer (EC)
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- Esophageal squamous cell carcinoma (ESCC)
- Disease progression on or since the most recent treatment (does not apply to newly diagnosed unresectable or metastatic HCC or EC).
- Measurable disease per RECIST v1.1 as assessed locally (by investigator) and verified by BICR
- Submission of an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
- Male participants are abstinent from heterosexual intercourse or agree to follow contraceptive guidance during and for at least 7 days after last dose of study intervention with belzutifan and lenvatinib
- Female participants are not pregnant or breastfeeding, not a woman of child-bearing potential (WOCBP), or is a WOCBP and agrees to follow contraceptive guidance during the intervention period and and for at least 120 days after the last dose of pembrolizumab or for at least 30 days after last dose of lenvatinib or belzutifan, whichever occurs last
- Adequate organ function
- Adequately controlled blood pressure with or without antihypertensive medications
- HCC Specific Inclusion Criteria: No prior systemic chemotherapy, including anti-VEGF therapy, anti-programmed cell-death (PD-1)/PD-L1 or any systemic investigational anticancer agents for advanced/unresectable HCC (1L)
- CRC ([non-MSI-H/dMMR) Specific Inclusion Criteria: Received at least 2 prior lines of systemic therapy for unresectable or metastatic disease which includes fluoropyrimidine, irinotecan and oxaliplatin
- PDAC Specific Inclusion Criteria: Prior therapy with at least 1 (platinum or gemcitabine containing regimen) but no more than 2 prior systemic therapies for unresectable or metastatic pancreatic cancer
- BTC Specific Inclusion Criteria: Received at least 1 prior line of systemic therapy (containing gemcitabine or fluoropyrimidine) for unresectable or metastatic disease
- EC Specific Inclusion Criteria: Study treatment is for 1L therapy of EC and participants should not have received prior systemic chemotherapy. Exception: May have received 1 prior line of line of systemic platinum-based adjuvant and/or neoadjuvant chemotherapy in the setting of a curative-intent resection, if the recurrence occurred ≥6 months after the last dose of chemotherapy or may have received prior radiation with or without chemotherapy
- ESCC Specific Inclusion Criteria: Have experienced radiographic or clinical progression on one prior line of standard systemic therapy (immune oncology (IO) naïve participants) or an anti-PD-1/PD-L1 (IO resistant participants)
Who cannot join
- Unable to swallow orally administered medication or presence of a gastrointestinal (GI) disorder that may affect study intervention absorption
- History of a second malignancy that is progressing or has required active treatment within 3 years
- A pulse oximeter reading <92% at rest, or requirement of intermittent supplemental oxygen/ chronic supplemental oxygen
- Presence of central nervous system (CNS) metastases and/or carcinomatous meningitis
- Clinically significant cardiovascular disease within 6 months of first dose of study intervention
- Symptomatic pleural effusion, unless clinically stable after treatment
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- Preexisting ≥ Grade 3 gastrointestinal (GI) or non-GI fistula
- Moderate to severe hepatic impairment
- Clinically significant history of bleeding within 3 months before screening
- Presence of serious active nonhealing wound/ulcer/bone fracture
- Requirement for hemodialysis or peritoneal dialysis
- History of human immunodeficiency virus (HIV) infection
- History of Hepatitis B or active Hepatis C virus infections. with exceptions for HCC and BTC
- Prior therapy with a PD-1, anti-PD-L1, anti-PD-L2 agent, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) or hypoxia-inducible factor 2α (HIF-2α)
- Radiographic evidence of intratumoral cavitation, or invasion/infiltration of a major blood vessel
- EC specific exclusion criteria: History of carcinosarcoma, endometrial leiomyosarcoma or other high-grade sarcomas, or endometrial stromal sarcomas
- ESCC specific exclusion criteria: Has clinically apparent ascites or pleural effusion or experienced weight loss >20% over approximately 3 months before first dose of study therapy
Trial locations and contacts
57 sites in 10 countries.
57 sites in 10 countries
United States16 sites
Johns Hopkins Hospital-Sidney Kimmel Comprehensive Cancer Center - GI and Immunology ( Site 5048)
Baltimore, Maryland, 21287
Brigitte Harris Cancer Pavilion ( Site 5055)
Detroit, Michigan, 48202
City of Hope Comprehensive Cancer Center ( Site 5002)
Duarte, California, 91010
Duke Cancer Institute ( Site 5026)
Durham, North Carolina, 27710
Inova Schar Cancer Institute ( Site 5039)
Fairfax, Virginia, 22031
University of Florida College of Medicine ( Site 5015)
Gainesville, Florida, 32610
University of Texas MD Anderson Cancer Center-Gastrointestinal Medical Oncology ( Site 5049)
Houston, Texas, 77030
Cedars-Sinai Medical Center ( Site 5045)
Los Angeles, California, 90048
University of Wisconsin Hospitals and Clinics ( Site 5037)
Madison, Wisconsin, 53792
Yale-New Haven Hospital-Yale Cancer Center ( Site 5013)
New Haven, Connecticut, 06510
Memorial Sloan Kettering Cancer Center ( Site 5050)
New York, New York, 10065
Blue Ridge Cancer Care ( Site 5053)
Roanoke, Virginia, 24014
UCSF Medical Center at Mission Bay ( Site 5021)
San Francisco, California, 94158
Northwest Medical Specialties, PLLC ( Site 5025)
Tacoma, Washington, 98405
University of Arizona Cancer Center-University of Arizona Cancer Center - North Campus ( Site 5047)
Tucson, Arizona, 85724
Sibley Memorial Hospital ( Site 5051)
Washington D.C., District of Columbia, 20016
France7 sites
Sainte Catherine Institut du Cancer Avignon Provence ( Site 1108)
Avignon, Vaucluse, 84000
CHU Besançon-Medical oncology ( Site 1101)
Besançon, Doubs, 25000
CHU Brest Cavale Blanche ( Site 1107)
Brest, Finistere, 29200
Hôpital Beaujon-Oncologie Digestive ( Site 1104)
Clichy, Île-de-France Region, 92110
Centre Hospitalier Universitaire de Grenoble-Medical Oncology ( Site 1105)
La Tronche, Isere, 38700
Institut Regional du Cancer Montpellier ( Site 1106)
Montpellier, Herault, 34298
Centre Eugène Marquis Rennes - Centre de Lutte Contre le Cancer ( Site 1103)
Rennes, Brittany Region, 35042
South Korea6 sites
Keimyung University Dongsan Hospital CRC room 1 ( Site 4104)
Daegu, Taegu-Kwangyokshi, 42601
Chonnam National University Hwasun Hospital-Hemato-Oncology ( Site 4105)
Hwasun Gun, Jeonranamdo, 58128
Seoul National University Hospital-Internal Medicine ( Site 4103)
Seoul, 03080
Severance Hospital, Yonsei University Health System-Medical oncology ( Site 4100)
Seoul, 03722
Asan Medical Center-Department of Oncology ( Site 4101)
Seoul, 05505
Samsung Medical Center-Division of Hematology/Oncology ( Site 4102)
Seoul, 06351
Belgium5 sites
Cliniques universitaires Saint-Luc-Medical Oncology ( Site 1001)
Brussels, Bruxelles-Capitale, Region de, 1200
Antwerp University Hospital-Oncology ( Site 1002)
Edegem, Antwerpen, 2650
UZ Leuven ( Site 1000)
Leuven, Vlaams-Brabant, 3000
Université Catholique de Louvain-Namur - Centre Hospitalier -Oncology ( Site 1003)
Namur, 5530
AZ Delta vzw ( Site 1004)
Roeselare, West-Vlaanderen, 8800
Chile5 sites
Clínica Puerto Montt ( Site 3110)
Port Montt, Los Lagos Region, 5500242
FALP-UIDO ( Site 3102)
Santiago, Region M. de Santiago, 7500921
Oncovida ( Site 3108)
Santiago, Region M. de Santiago, 7510032
Bradfordhill-Clinical Area ( Site 3100)
Santiago, Region M. de Santiago, 8420383
Centro Investigación del Cáncer James Lind ( Site 3107)
Temuco, Araucania, 4800827
Spain5 sites
Hospital Germans Trias i Pujol-Instituto Catalán de Oncología de Badalona ( Site 1806)
Badalona, Barcelona, 08916
Hospital Universitari Vall d'Hebron-Oncology ( Site 1800)
Barcelona, 08035
HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 1801)
Madrid, Madrid, Comunidad de, 28007
Hospital Universitario Central de Asturias-Medical Oncology ( Site 1802)
Oviedo, Principality of Asturias, 33011
CHUS - Hospital Clinico Universitario-Servicio de Oncologia ( Site 1807)
Santiago de Compostela, La Coruna, 15706
Australia4 sites
Northern Hospital-Department of Medical Oncology ( Site 4003)
Epping, Victoria, 3076
Gosford Hospital-Oncology Trials ( Site 4004)
Gosford, New South Wales, 2250
Cabrini Hospital - Malvern-Cabrini Institute ( Site 4000)
Malvern, Victoria, 3144
Westmead Hospital-Department of Medical Oncology ( Site 4001)
Westmead, New South Wales, 2145
Israel4 sites
Rambam Health Care Campus-Oncology ( Site 1300)
Haifa, 3109601
Hadassah Medical Center-Oncology ( Site 1303)
Jerusalem, 9112001
Sheba Medical Center-ONCOLOGY ( Site 1302)
Ramat Gan, 5265601
Sourasky Medical Center-Oncology ( Site 1301)
Tel Aviv, 6423906
Netherlands3 sites
Leids Universitair Medisch Centrum-Medical Oncology ( Site 1504)
Leiden, South Holland, 2333 ZA
Maastricht UMC+-Medical Oncology ( Site 1501)
Maastricht, Limburg, 6229 HX
Universitair Medisch Centrum Utrecht-Medical Oncology ( Site 1503)
Utrecht, 3584 CX
New Zealand2 sites
Auckland City Hospital-Cancer & Blood Research ( Site 4200)
Auckland, 1023
Auckland City Hospital-Liver Research Unit ( Site 4201)
Grafton, Auckland, 1023
About this study
Official title: An Open-label, Multicenter, Phase 2 Study to Evaluate the Efficacy and Safety of Pembrolizumab Plus Lenvatinib in Combination With Belzutifan in Multiple Solid Tumors
The purpose of this study is to determine the safety and efficacy of belzutifan in combination with pembrolizumab and lenvatinib in multiple solid tumors including hepatocellular carcinoma (HCC), colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), biliary tract cancer (BTC), endometrial cancer (EC),and esophageal squamous cell carcinoma (ESCC). There is no formal hypothesis testing in this study.
Read the detailed description
Effective as of Amendment 3 (26 Mar 2025), enrollment of participants with ESCC will be closed.
- Conditions
- Neoplasm Malignant
- Being tested
- Pembrolizumab, Belzutifan, Lenvatinib
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called MK-3475, KEYTRUDA®
Pembrolizumab 400 mg administered Q6W via IV infusion
BelzutifanDrug
Also called MK-6482, PT2977, WELIREG™
Belzutifan 120 mg administered QD via oral tablet
LenvatinibDrug
Also called MK-7902, E7080, LENVIMA®
Lenvantinib dose for HCC is 8 mg QD for body weight <60 kg and 12 mg QD for body weight ≥ 60 kg administered via oral capsule. For all other tumors, the lenvatinib dose is 20 mg QD administered via oral capsule
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Pembrolizumab + Belzutifan + Lenvatinib | Experimental | Participants will receive pembrolizumab 400 mg PLUS belzutifan 120 mg PLUS lenvatinib 20 mg (For HCC: 8 mg [body weight <60kg] or 12 mg [body weight ≥ 60 kg]). Pembrolizumab will be administered via intravenous (IV) infusion once every 6 weeks (Q6W) for a maximum of 18 doses (approximately 2 years). Belzutifan and lenvatinib will be administered orally once daily (QD) until progressive disease or discontinuation. Receives: Drug: Pembrolizumab; Drug: Belzutifan; Drug: Lenvatinib |
| Arm 2: Pembrolizumab + Lenvatinib | Experimental | Participants with IO resistant ESCC will receive pembrolizumab 400 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered via intravenous (IV) infusion once every 6 weeks (Q6W) for a maximum of 18 doses (approximately 2 years). Lenvatinib will be administered orally once daily (QD) until progressive disease or discontinuation. Receives: Drug: Pembrolizumab; Drug: Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Arm 1: Number of Participants Who Experience at Least One Dose-limiting Toxicity (DLT)
Occurrence of any of the following will be considered a DLT if possibly, probably, or definitely related to study treatment administration: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting >7 days; Grade 4 thrombocytopenia-any duration; Grade 3 thrombocytopenia if associated with clinically significant hemorrhage; Febrile neutropenia Grade 3 or Grade 4; Grade 3 nonhematologic toxicity lasting >5 days despite optimal supportive care; Grade 3 hypertension not controlled by antihypertensive medication(s); Grade 3 or Grade 4 nonhematologic laboratory abnormality (if medical intervention is required, or leads to hospitalization, or persists for >1 week) ; Elevated bilirubin if persists >4 weeks (for HCC and BTC participants only); Designated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) liver test abnormalities; Treatment-related toxicity resulting in participant discontinuation of study intervention during the DLT window; Grade 5 toxicity.
Measured: Up to approximately 21 days
Arm 1: Number of Participants Who Experience at Least One Adverse Event (AE)
An AE is defined as 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 one or more AEs will be presented.
Measured: Up to approximately 67 months
Arm 1: Number of Participants Who Discontinue Study Treatment Due to an AE
An AE is defined as 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 separately for the safety lead-in phase (up to 21 days) and the main study.
Measured: Up to approximately 67 months
Confirmed Objective Response Rate (ORR) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
ORR is defined as the percentage of participants with 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 RECIST 1.1. The percentage of participants who experience CR or PR as assessed by BICR will be presented.
Measured: Up to approximately 67 months
Secondary outcomes (10)
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
For participants who demonstrate a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR 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 BICR will be presented.
Measured: Up to approximately 67 months
Disease Control Rate (DCR) Per RECIST 1.1 as Assessed by BICR
DCR is defined as the percentage of participants who have a CR, PR, or Stable Disease (SD). Per RECIST 1.1, CR = disappearance of all target lesions, PR = ≥30% decrease in the sum of product diameters (SPD) of target lesions, compared to baseline SPD, and SD = neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. The best overall response of CR, PR, or SD after ≥ 6 weeks will be assessed per RECIST 1.1 by BICR.
Measured: Up to approximately 67 months
Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by BICR
PFS is defined as the time from first day of study intervention to the first documented PD or death due to any cause, whichever occurs first as assessed by RECIST 1.1. 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. PFS as assessed by BICR will be presented.
Measured: Up to approximately 67 months
Overall Survival (OS)
OS is defined as the time from the first day of study intervention to death due to any cause.
Measured: Up to approximately 67 months
ORR Per Modified Response Criteria in Solid Tumors Version 1.1 (mRECIST 1.1) for Hepatocellular Carcinoma (HCC) as Assessed by BICR
ORR, per mRECIST 1.1, is defined as the percentage of participants with CR (disappearance of any intratumoral arterial enhancement in all target lesions) or PR (at least a 30% decrease in the sum of diameters of viable [contrast enhancement in the arterial phase] target lesions, taking as reference the baseline sum of diameters of target lesions) as assessed by BICR. For participants with HCC, mRECIST1.1 allows assessment of treatment-related tumor necrosis and assessment of viable tumor by assessment with arterial phase imaging. ORR as assessed by BICR will be presented.
Measured: Up to approximately 67 months
DOR Per mRECIST 1.1 for HCC as Assessed by BICR
For participants who demonstrate a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in sum of diameters of target lesions) per mRECIST 1.1, DOR is defined as time from first documented evidence of CR or PR until progressive disease (PD) or death. Per mRECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters (SOD) 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. The mRECIST 1.1 this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. For participants with HCC, mRECIST1.1 allows assessment of treatment-related tumor necrosis and assessment of viable tumor by assessment with arterial phase imaging. DOR as assessed by BICR will be presented.
Measured: Up to approximately 67 months
DCR Per mRECIST 1.1 for HCC as Assessed by BICR
DCR is defined, per mRECIST 1.1, as the percentage of participants who have a CR (Disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease (SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD [At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]). For participants with HCC, mRECIST1.1 allows assessment of treatment-related tumor necrosis and assessment of viable tumor by assessment with arterial phase imaging. The best overall response of CR, PR, or SD after ≥ 6 weeks per mRECIST 1.1 for HCC will be assessed by BICR.
Measured: Up to approximately 67 months
PFS Per mRECIST 1.1 for HCC as Assessed by BICR
PFS, per mRECIST 1.1, is defined as the time from first dose of study treatment to the first documented PD or death due to any cause, whichever occurs first as assessed by mRECIST1.1 to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. Per mRECIST 1.1, 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. For participants with HCC, mRECIST1.1 allows assessment of treatment-related tumor necrosis and assessment of viable tumor by assessment with arterial phase imaging. PFS as assessed by BICR will be presented.
Measured: Up to approximately 67 months
Arm 2: Number of Participants Who Experience an AE
An AE is defined as 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 after administration of pembrolizumab plus lenvatinib will be presented.
Measured: Up to approximately 67 months
Arm 2: Number of Participants Who Discontinued Study Treatment Due to an AE
An AE is defined as 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 of pembrolizumab plus lenvatinib after an AE will be presented.
Measured: Up to approximately 67 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2021
- Study start18 Aug 2021
- Primary completion22 Mar 2027 (estimated)
- Study completion22 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neoplasm MalignantStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 730 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04976634
- Sponsor's protocol ID
- 6482-016
- Other IDs
- MK-6482-016, 2023-503905-12-00, U1111-1288-3020, 2020-005007-40, 2023
- Status last verified
- Apr 2025
- First submitted
- 16 Jul 2021
- Last updated
- 6 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
Gebrael G, Sahu KK, Agarwal N, Maughan BL. Update on combined immunotherapy for the treatment of advanced renal cell carcinoma. Hum Vaccin Immunother. 2023 Dec 31;19(1):2193528. doi: 10.1080/21645515.2023.2193528. Epub 2023 Apr 16.
PubMed 37062953
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multicenter, Phase 2 Study to Evaluate the Efficacy and Safety of Pembrolizumab Plus Lenvatinib in Combination With Belzutifan in Multiple Solid Tumors
- ClinicalTrials.gov ID
- NCT04976634
- Acronym / sponsor ID
- 6482-016
- Conditions
- Neoplasm Malignant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 730 participants (estimated)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 18 Aug 2021 (actual)
- Primary completion
- 22 Mar 2027 (estimated)
- Study completion
- 22 Mar 2027 (estimated)
- First posted
- 26 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the safety and efficacy of belzutifan in combination with pembrolizumab and lenvatinib in multiple solid tumors including hepatocellular carcinoma (HCC), colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), biliary tract cancer (BTC), endometrial cancer (EC),and esophageal squamous cell carcinoma (ESCC). There is no formal hypothesis testing in this study.
Detailed description
Effective as of Amendment 3 (26 Mar 2025), enrollment of participants with ESCC will be closed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Pembrolizumab + Belzutifan + Lenvatinib | Experimental | Drug: Pembrolizumab, Drug: Belzutifan, Drug: LenvatinibParticipants will receive pembrolizumab 400 mg PLUS belzutifan 120 mg PLUS lenvatinib 20 mg (For HCC: 8 mg [body weight <60kg] or 12 mg [body weight ≥ 60 kg]). Pembrolizumab will be administered via intravenous (IV) infusion once every 6 weeks (Q6W) for a maximum of 18 doses (approximately 2 years). Belzutifan and lenvatinib will be administered orally once daily (QD) until progressive disease or discontinuation. |
| Arm 2: Pembrolizumab + Lenvatinib | Experimental | Drug: Pembrolizumab, Drug: LenvatinibParticipants with IO resistant ESCC will receive pembrolizumab 400 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered via intravenous (IV) infusion once every 6 weeks (Q6W) for a maximum of 18 doses (approximately 2 years). Lenvatinib will be administered orally once daily (QD) until progressive disease or discontinuation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Diagnosis of one of the following advanced (unresectable and/or metastatic) solid tumors, documented by histopathology or cytopathology:
- Disease progression on or since the most recent treatment (does not apply to newly diagnosed unresectable or metastatic HCC or EC).
- Measurable disease per RECIST v1.1 as assessed locally (by investigator) and verified by BICR
- Submission of an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
- Male participants are abstinent from heterosexual intercourse or agree to follow contraceptive guidance during and for at least 7 days after last dose of study intervention with belzutifan and lenvatinib
Key exclusion criteria (17 listed)
- Unable to swallow orally administered medication or presence of a gastrointestinal (GI) disorder that may affect study intervention absorption
- History of a second malignancy that is progressing or has required active treatment within 3 years
- A pulse oximeter reading <92% at rest, or requirement of intermittent supplemental oxygen/ chronic supplemental oxygen
- Presence of central nervous system (CNS) metastases and/or carcinomatous meningitis
- Clinically significant cardiovascular disease within 6 months of first dose of study intervention
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: MK-3475, KEYTRUDA®Pembrolizumab 400 mg administered Q6W via IV infusion | Drug | Arm 1: Pembrolizumab + Belzutifan + Lenvatinib, Arm 2: Pembrolizumab + Lenvatinib |
| BelzutifanAlso: MK-6482, PT2977, WELIREG™Belzutifan 120 mg administered QD via oral tablet | Drug | Arm 1: Pembrolizumab + Belzutifan + Lenvatinib |
| LenvatinibAlso: MK-7902, E7080, LENVIMA®Lenvantinib dose for HCC is 8 mg QD for body weight <60 kg and 12 mg QD for body weight ≥ 60 kg administered via oral capsule. For all other tumors, the lenvatinib dose is 20 mg QD administered via oral capsule | Drug | Arm 1: Pembrolizumab + Belzutifan + Lenvatinib, Arm 2: Pembrolizumab + Lenvatinib |
Primary outcome
Arm 1: Number of Participants Who Experience at Least One Dose-limiting Toxicity (DLT)
Time frame: Up to approximately 21 days
Occurrence of any of the following will be considered a DLT if possibly, probably, or definitely related to study treatment administration: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting >7 days; Grade 4 thrombocytopenia-any duration; Grade 3 thrombocytopenia if associated with clinically significant hemorrhage; Febrile neutropenia Grade 3 or Grade 4; Grade 3 nonhematologic toxicity lasting >5 days despite optimal supportive care; Grade 3 hypertension not controlled by antihypertensive medication(s); Grade 3 or Grade 4 nonhematologic laboratory abnormality (if medical intervention is required, or leads to hospitalization, or persists for >1 week) ; Elevated bilirubin if persists >4 weeks (for HCC and BTC participants only); Designated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) liver test abnormalities; Treatment-related toxicity resulting in participant discontinuation of study intervention during the DLT window; Grade 5 toxicity.
Arm 1: Number of Participants Who Experience at Least One Adverse Event (AE)
Time frame: Up to approximately 67 months
An AE is defined as 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 one or more AEs will be presented.
Arm 1: Number of Participants Who Discontinue Study Treatment Due to an AE
Time frame: Up to approximately 67 months
An AE is defined as 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 separately for the safety lead-in phase (up to 21 days) and the main study.
Confirmed Objective Response Rate (ORR) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Time frame: Up to approximately 67 months
ORR is defined as the percentage of participants with 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 RECIST 1.1. The percentage of participants who experience CR or PR as assessed by BICR will be presented.
10 secondary outcomes
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
Time frame: Up to approximately 67 months
Disease Control Rate (DCR) Per RECIST 1.1 as Assessed by BICR
Time frame: Up to approximately 67 months
Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by BICR
Time frame: Up to approximately 67 months
Overall Survival (OS)
Time frame: Up to approximately 67 months
ORR Per Modified Response Criteria in Solid Tumors Version 1.1 (mRECIST 1.1) for Hepatocellular Carcinoma (HCC) as Assessed by BICR
Time frame: Up to approximately 67 months
DOR Per mRECIST 1.1 for HCC as Assessed by BICR
Time frame: Up to approximately 67 months
DCR Per mRECIST 1.1 for HCC as Assessed by BICR
Time frame: Up to approximately 67 months
PFS Per mRECIST 1.1 for HCC as Assessed by BICR
Time frame: Up to approximately 67 months
Arm 2: Number of Participants Who Experience an AE
Time frame: Up to approximately 67 months
Arm 2: Number of Participants Who Discontinued Study Treatment Due to an AE
Time frame: Up to approximately 67 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2025.
- Derived from this study: PubMed 37062953Gebrael G, Sahu KK, Agarwal N, Maughan BL. Update on combined immunotherapy for the treatment of advanced renal cell carcinoma. Hum Vaccin Immunother. 2023 Dec 31;19(1):2193528. doi: 10.1080/21645515.2023.2193528. Epub 2023 Apr 16.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
57 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab, Belzutifan and Lenvatinib in people with Neoplasm Malignant, run by Merck Sharp & Dohme LLC at 57 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 6 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 57 sites in United States, France, South Korea, Belgium, Chile and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Arm 1: Number of Participants Who Experience at Least One Dose-limiting Toxicity (DLT) (time frame: Up to approximately 21 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04976634, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2025.