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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04976634




Registration number
NCT04976634
Ethics application status
Date submitted
16/07/2021
Date registered
26/07/2021

Titles & IDs
Public title
Pembrolizumab Plus Lenvatinib in Combination With Belzutifan in Solid Tumors (MK-6482-016)
Scientific 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
Secondary ID [1] 0 0
MK-6482-016
Secondary ID [2] 0 0
6482-016
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Hepatocellular 0 0
Colorectal Neoplasms 0 0
Pancreatic Ductal Adenocarcinoma 0 0
Biliary Tract Neoplasms 0 0
Endometrial Neoplasms 0 0
Esophageal Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 0 0 0 0
Liver
Cancer 0 0 0 0
Oesophageal (gullet)
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)
Cancer 0 0 0 0
Biliary tree (gall bladder and bile duct)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Belzutifan
Treatment: Drugs - Lenvatinib

Experimental: Arm 1: Pembrolizumab + Belzutifan + Lenvatinib - 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.

Experimental: Arm 2: Pembrolizumab + Lenvatinib - 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.


Treatment: Drugs: Pembrolizumab
Pembrolizumab 400 mg administered Q6W via IV infusion

Treatment: Drugs: Belzutifan
Belzutifan 120 mg administered QD via oral tablet

Treatment: Drugs: Lenvatinib
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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Arm 1: Number of Participants Who Experience at Least One Dose-limiting Toxicity (DLT)
Timepoint [1] 0 0
Up to approximately 21 days
Primary outcome [2] 0 0
Arm 1: Number of Participants Who Experience at Least One Adverse Event (AE)
Timepoint [2] 0 0
Up to approximately 60 months
Primary outcome [3] 0 0
Arm 1: Number of Participants Who Discontinue Study Treatment Due to an AE
Timepoint [3] 0 0
Up to approximately 59 months
Primary outcome [4] 0 0
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)
Timepoint [4] 0 0
Up to approximately 60 months
Secondary outcome [1] 0 0
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
Timepoint [1] 0 0
Up to approximately 60 months
Secondary outcome [2] 0 0
Disease Control Rate (DCR) Per RECIST 1.1 as Assessed by BICR
Timepoint [2] 0 0
Up to approximately 60 months
Secondary outcome [3] 0 0
Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by BICR
Timepoint [3] 0 0
Up to approximately 60 months
Secondary outcome [4] 0 0
Overall Survival (OS)
Timepoint [4] 0 0
Up to approximately 60 months
Secondary outcome [5] 0 0
ORR Per Modified Response Criteria in Solid Tumors Version 1.1 (mRECIST 1.1) for Hepatocellular Carcinoma (HCC) as Assessed by BICR
Timepoint [5] 0 0
Up to approximately 60 months
Secondary outcome [6] 0 0
DOR Per mRECIST 1.1 for HCC as Assessed by BICR
Timepoint [6] 0 0
Up to approximately 60 months
Secondary outcome [7] 0 0
DCR Per mRECIST 1.1 for HCC as Assessed by BICR
Timepoint [7] 0 0
Up to approximately 60 months
Secondary outcome [8] 0 0
PFS Per mRECIST 1.1 for HCC as Assessed by BICR
Timepoint [8] 0 0
Up to approximately 60 months
Secondary outcome [9] 0 0
Arm 2: Number of Participants Who Experienced an Adverse Event (AE)
Timepoint [9] 0 0
Up to approximately 60 months
Secondary outcome [10] 0 0
Arm 2: Number of Participants Who Discontinued Study Treatment Due to an AE
Timepoint [10] 0 0
Up to approximately 59 months

Eligibility
Key inclusion criteria
* 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)
* 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 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 Received at least 2 prior lines of systemic therapy for unresectable or metastatic disease which includes fluoropyrimidine, irinotecan and oxaliplatin
* PDAC Specific 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 Received at least 1 prior line of systemic therapy (containing gemcitabine or fluoropyrimidine) for unresectable or metastatic disease
* EC Specific 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 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)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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
* 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 2a (HIF-2a)
* 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/08/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
22/03/2027
Actual
Sample size
Target
730
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Gosford Hospital-Oncology Trials ( Site 4004) - Gosford
Recruitment hospital [2] 0 0
Westmead Hospital-Department of Medical Oncology ( Site 4001) - Westmead
Recruitment hospital [3] 0 0
Northern Hospital-Department of Medical Oncology ( Site 4003) - Epping
Recruitment hospital [4] 0 0
Cabrini Hospital - Malvern-Cabrini Institute ( Site 4000) - Malvern
Recruitment postcode(s) [1] 0 0
2250 - Gosford
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
3076 - Epping
Recruitment postcode(s) [4] 0 0
3144 - Malvern
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
United States of America
State/province [13] 0 0
Wisconsin
Country [14] 0 0
Belgium
State/province [14] 0 0
Antwerpen
Country [15] 0 0
Belgium
State/province [15] 0 0
Bruxelles-Capitale, Region De
Country [16] 0 0
Belgium
State/province [16] 0 0
Vlaams-Brabant
Country [17] 0 0
Belgium
State/province [17] 0 0
West-Vlaanderen
Country [18] 0 0
Belgium
State/province [18] 0 0
Namur
Country [19] 0 0
Chile
State/province [19] 0 0
Araucania
Country [20] 0 0
Chile
State/province [20] 0 0
Los Lagos
Country [21] 0 0
Chile
State/province [21] 0 0
Region M. De Santiago
Country [22] 0 0
France
State/province [22] 0 0
Bretagne
Country [23] 0 0
France
State/province [23] 0 0
Doubs
Country [24] 0 0
France
State/province [24] 0 0
Finistere
Country [25] 0 0
France
State/province [25] 0 0
Herault
Country [26] 0 0
France
State/province [26] 0 0
Ile-de-France
Country [27] 0 0
France
State/province [27] 0 0
Isere
Country [28] 0 0
France
State/province [28] 0 0
Vaucluse
Country [29] 0 0
Israel
State/province [29] 0 0
Haifa
Country [30] 0 0
Israel
State/province [30] 0 0
Jerusalem
Country [31] 0 0
Israel
State/province [31] 0 0
Ramat Gan
Country [32] 0 0
Israel
State/province [32] 0 0
Tel Aviv
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Jeonranamdo
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Taegu-Kwangyokshi
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Seoul
Country [36] 0 0
Netherlands
State/province [36] 0 0
Limburg
Country [37] 0 0
Netherlands
State/province [37] 0 0
Zuid-Holland
Country [38] 0 0
Netherlands
State/province [38] 0 0
Utrecht
Country [39] 0 0
New Zealand
State/province [39] 0 0
Auckland
Country [40] 0 0
Spain
State/province [40] 0 0
Asturias
Country [41] 0 0
Spain
State/province [41] 0 0
Barcelona
Country [42] 0 0
Spain
State/province [42] 0 0
La Coruna
Country [43] 0 0
Spain
State/province [43] 0 0
Madrid, Comunidad De

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04976634