Clinical Trials /

Safety and Efficacy of Coformulated Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib (E7080/MK-7902) in Advanced Hepatocellular Carcinoma (MK-1308A-004)

NCT04740307

Description:

The purpose of this study is to evaluate the safety and efficacy of fixed dose coformulated pembrolizumab/quavonlimab (MK-1308A) plus lenvatinib in a first line (1L) hepatocellular carcinoma (HCC) setting. No hypothesis testing will be performed.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy of Coformulated Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib (E7080/MK-7902) in Advanced Hepatocellular Carcinoma (MK-1308A-004)
  • Official Title: A Phase 2, Multicenter, Clinical Study to Evaluate the Safety and Efficacy of MK-1308A (Coformulated MK-1308/MK-3475) in Combination With Lenvatinib (E7080/MK-7902) in First-line Therapy of Participants With Advanced Hepatocellular Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: 1308A-004
  • SECONDARY ID: 2020-004490-52
  • SECONDARY ID: MK-1308A-004
  • NCT ID: NCT04740307

Conditions

  • Advanced Hepatocellular Carcinoma

Interventions

DrugSynonymsArms
Pembrolizumab/QuavonlimabMK-1308APembrolizumab/Quavonlimab + Lenvatinib
LenvatinibMK-7902Pembrolizumab/Quavonlimab + Lenvatinib
PembrolizumabMK-3475, KEYTRUDA®Pembrolizumab/Quavonlimab + Lenvatinib

Purpose

The purpose of this study is to evaluate the safety and efficacy of fixed dose coformulated pembrolizumab/quavonlimab (MK-1308A) plus lenvatinib in a first line (1L) hepatocellular carcinoma (HCC) setting. No hypothesis testing will be performed.

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab/Quavonlimab + LenvatinibExperimentalParticipants receive pembrolizumab/quavonlimab via intravenous (IV) infusion every 6 weeks (Q6W) for up to 2 years, plus lenvatinib orally (based on actual body weight at screening) until progressive disease or unacceptable toxicity for up to 5 years. In the event of discontinuation of pembrolizumab/quavonlimab due to intolerable toxicity, re-initiation of treatment with pembrolizumab may be considered.
  • Pembrolizumab/Quavonlimab
  • Lenvatinib
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Has an HCC diagnosis confirmed by radiology, histology, or cytology (fibrolamellar and
             mixed hepatocellular/cholangiocarcinoma subtypes are not eligible)

          -  Has Barcelona Clinic Liver Cancer (BCLC) Stage C disease, or BCLC Stage B disease not
             amenable to locoregional therapy or refractory to locoregional therapy, and not
             amenable to a curative treatment approach

          -  Has a Child-Pugh class A liver score within 7 days prior to first dose of study
             intervention

          -  Has a predicted life expectancy of >3 months

          -  Has at least 1 measurable HCC lesion based on RECIST 1.1, confirmed by BICR

          -  Has an Eastern Cooperative Oncology Group Performance Score (ECOG PS) of 0 to 1 within
             7 days prior to first dose of study intervention

          -  Participants with controlled hepatitis B will be eligible as long as they meet the
             following criteria: antiviral therapy for Hepatitis B virus (HBV) must be given for at
             least 4 weeks and HBV viral load must be less than 500 IU/mL prior to first dose of
             study drug

          -  Has adequately controlled blood pressure with or without antihypertensive medications

          -  Has adequate organ function

        Exclusion Criteria:

          -  Has had esophageal or gastric variceal bleeding within the last 6 months.

          -  Has bleeding or thrombotic disorders or use of factor X inhibitors or anticoagulants
             requiring therapeutic international normalized ratio (INR) monitoring, e.g., warfarin
             or similar agents

          -  Has clinically apparent ascites on physical examination

          -  Has inferior vena cava or cardiac involvement of HCC based on imaging

          -  Has had clinically diagnosed hepatic encephalopathy in the last 6 months unresponsive
             to therapy

          -  Has medical contraindications that preclude all forms of contrast-enhanced imaging
             (computed tomography [CT] or magnetic resonance imaging [MRI])

          -  Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other
             condition that might affect the absorption of lenvatinib

          -  Has a preexisting Grade ≥3 gastrointestinal or non-gastrointestinal fistula

          -  Has clinically active hemoptysis (bright red blood of a least 0.5 teaspoon) within 3
             weeks prior to the first dose of study drug

          -  Has clinically significant cardiovascular impairment within 12 months of the first
             dose of study intervention, including New York Heart Association (NYHA) Class III or
             IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular
             accident, or cardiac arrhythmia associated with hemodynamic instability

          -  Has had major surgery to the liver within 4 weeks prior to the first dose of study
             intervention

          -  Has had a minor surgery (i.e., simple excision) within 7 days prior to the first dose
             of study intervention (Cycle 1 Day 1)

          -  Has serious nonhealing wound, ulcer, or bone fracture

          -  Has received any systemic chemotherapy, including anti- vascular endothelial growth
             factor (VEGF) therapy, or any systemic investigational anticancer agents for treatment
             of HCC

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with
             an agent directed to another stimulatory or coinhibitory T-cell receptor

          -  Has received locoregional therapy to liver within 4 weeks prior to the first dose of
             study intervention

          -  Has received prior radiotherapy to a non-liver region within 2 weeks of start of study
             intervention

          -  Has received a live or live-attenuated vaccine within 30 days before the first dose of
             study drug

          -  Is currently participating in or has participated in a study of an investigational
             agent or has used an investigational device within 4 weeks prior to the first dose of
             study intervention

          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             or any other form of immunosuppressive therapy within 7 days prior 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 a known history of, or any evidence of, central nervous system (CNS) metastases
             and/or carcinomatous meningitis as assessed by local site investigator

          -  Has severe hypersensitivity (≥Grade 3) to study intervention and/or any of their
             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, with the exception of HBV or
             Hepatitis C virus (HCV)

          -  Has a known history of human immunodeficiency virus (HIV) infection

          -  Has dual active HBV infection (HBsAg (+) and /or detectable HBV DNA) and HCV infection
             (anti-HCV antibody [Ab] positive and detectable HCV RNA) at study entry

          -  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 a known psychiatric or substance abuse disorder that would interfere with the
             participants ability to cooperate with the requirements of the study

          -  Has had an allogenic tissue/solid organ transplant
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with a Dose-Limiting Toxicity (DLT) in the Safety Lead-in Phase
Time Frame:Cycle 1 (Up to approximately 3 weeks)
Safety Issue:
Description:DLTs will be defined as follows unless determined to be unrelated to study intervention: any Grade 4 nonhematologic toxicity (not laboratory); any Grade 4 hematologic toxicity lasting >7 days (Grade 4 lymphopenia lasting ≥21 days); Grade 3 platelet count decreased if associated with clinically significant hemorrhage; any Grade 3 nonhematologic toxicity (not laboratory) lasting >3 days despite optimal supportive care; any clinically significant Grade 3 or Grade 4 nonhematologic laboratory abnormality if: medical intervention is required to treat participant, or abnormality leads to hospitalization, or abnormality persists for >1 week (or bilirubin if persists >4 weeks); aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) >10.0 times upper limit of normal (ULN) or >10.0 times baseline if baseline >ULN; any febrile neutropenia Grade 3 or Grade 4; any treatment-related AE that causes the participant to discontinue study intervention during the DLT window; any Grade 5 toxicity

Secondary Outcome Measures

Measure:Duration of Response (DOR) per RECIST 1.1 as assessed by BICR
Time Frame:Up to approximately 28 months
Safety Issue:
Description:For participants who demonstrate confirmed CR or PR per RECIST 1.1 assessed by BICR, DOR is defined as the time from the first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the SOD of target lesions) until progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1 adjusted for this study to allow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as at least a 20% increase in the 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.
Measure:Disease Control Rate (DCR) per RECIST 1.1 as assessed by BICR
Time Frame:Up to approximately 28 months
Safety Issue:
Description:DCR is defined as the percentage of participants who have achieved CR (disappearance of all target lesions), PR (at least a 30% decrease in the SOD of target lesions), or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD) after ≥6 weeks (the start of the window for the first scheduled scan) per RECIST 1.1 assessed by BICR. Per RECIST 1.1 adjusted for this study to allow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as at least a 20% increase in the 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.
Measure:Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR
Time Frame:Up to approximately 28 months
Safety Issue:
Description:PFS is defined as the time from the first dose of study intervention to the first documented PD per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. Per RECIST 1.1 adjusted for this study to allow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as at least a 20% increase in the 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.
Measure:Time-To-Progression (TTP) per RECIST 1.1 as assessed by BICR
Time Frame:Up to approximately 28 months
Safety Issue:
Description:TTP is defined as the time from the first dose of study intervention to the first documented PD per RECIST 1.1 assessed by BICR. Per RECIST 1.1 adjusted for this study to allow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as at least a 20% increase in the 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.
Measure:Overall Survival (OS)
Time Frame:Up to approximately 28 months
Safety Issue:
Description:OS is defined as the time from the first dose of study intervention to death due to any cause.
Measure:ORR per modified RECIST (mRECIST) as assessed by BICR
Time Frame:Up to approximately 28 months
Safety Issue:
Description:ORR is defined as the percentage of participants who achieve a confirmed CR (disappearance of any intratumoral arterial enhancement in all target lesions) or a PR (at least a 30% decrease in the SOD of viable [contrast enhancement in the arterial phase] target lesions, taking as reference the baseline SOD of target lesions) per mRECIST as assessed by BICR. mRECIST for HCC allows evaluation of treatment effects that are not reflected in simple total size changes of lesions.
Measure:DOR per mRECIST as assessed by BICR
Time Frame:Up to approximately 28 months
Safety Issue:
Description:For participants who demonstrate confirmed CR or PR per mRECIST assessed by BICR, DOR is defined as the time from the first documented evidence of CR (disappearance of any intratumoral arterial enhancement in all target lesions) or PR (at least a 30% decrease in the SOD of viable [contrast enhancement in the arterial phase] target lesions, taking as reference the baseline SOD of target lesions) until PD or death due to any cause, whichever occurs first. mRECIST for HCC allows evaluation of treatment effects that are not reflected in simple total size changes of lesions. Per mRECIST, PD was defined as an increase of at least 20% in the SODs of viable (enhancing) target lesions, taking as reference the smallest SODs of viable (enhancing) target lesions recorded since the treatment started.
Measure:DCR per mRECIST as assessed by BICR
Time Frame:Up to approximately 28 months
Safety Issue:
Description:DCR is defined as the percentage of participants who have achieved CR (disappearance of any intratumoral arterial enhancement in all target lesions), PR (at least a 30% decrease in the SOD of viable [contrast enhancement in the arterial phase] target lesions, taking as reference the baseline SOD of target lesions), or SD (any cases that do not qualify for either PR or PD) after ≥6 weeks (the start of the window for the first scheduled scan) per mRECIST assessed by BICR. mRECIST for HCC allows evaluation of treatment effects that are not reflected in simple total size changes of lesions. Per mRECIST, PD was defined as an increase of at least 20% in the SODs of viable (enhancing) target lesions, taking as reference the smallest SODs of viable (enhancing) target lesions recorded since the treatment started.
Measure:PFS per mRECIST as assessed by BICR
Time Frame:Up to approximately 28 months
Safety Issue:
Description:PFS is defined as the time from the first dose of study intervention to the first documented PD per mRECIST by BICR or death due to any cause, whichever occurs first. mRECIST for HCC allows evaluation of treatment effects that are not reflected in simple total size changes of lesions. Per mRECIST, PD was defined as an increase of at least 20% in the SODs of viable (enhancing) target lesions, taking as reference the smallest SODs of viable (enhancing) target lesions recorded since the treatment started.
Measure:TTP per mRECIST as assessed by BICR
Time Frame:Up to approximately 28 months
Safety Issue:
Description:TTP is defined as the time from the first dose of study intervention to the first documented PD per mRECIST assessed by BICR. mRECIST for HCC allows evaluation of treatment effects that are not reflected in simple total size changes of lesions. Per mRECIST, PD was defined as an increase of at least 20% in the SODs of viable (enhancing) target lesions, taking as reference the smallest SODs of viable (enhancing) target lesions recorded since the treatment started.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
  • Programmed Cell Death-1 (PD1, PD-1)
  • Programmed Death-Ligand 1 (PDL1, PD-L1)
  • Programmed Death-Ligand 2 (PDL2, PD-L2)
  • receptor tyrosine kinase inhibitor

Last Updated

May 3, 2021