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

NCT04740307 | Completed Phase 2 FDA Drug

• 6 other identifiers: 1308A-004MK-1308A-004jRCT20612100332023-505698-34-00U1111-1292-31582020-004490-52
• Study Type: interventional
• Target: 116
• Locations: 9 countries
• Sites: 40

Brief Summary

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.

Conditions

Advanced Hepatocellular Carcinoma

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

Outcome Measures

Primary Outcomes (7)

• Number of participants with a Dose-Limiting Toxicity (DLT) in the Safety Lead-in Phase

  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

  Cycle 1 (Up to approximately 3 weeks)

• Number of participants with ≥1 adverse event (AE)

  An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants with an AE will be reported.

  Up to approximately 5 years

• Number of participants with ≥1 serious adverse event (SAE)

  An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is another important medical event. The number of participants with an SAE will be reported.

  Up to approximately 5 years

• Number of participants with ≥1 immune-related AE (irAE)

  An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. AEs associated with MK-1308A exposure may represent an immune-related response. irAEs pre-specified for this study include pneumonitis, diarrhea/colitis, Type 1 diabetes mellitus (T1DM) or hyperglycemia, hypophysitis, hyperthyroidism, hypothyroidism, nephritis (grading according to increased creatinine or acute kidney injury), and myocarditis. The number of participants with an irAE will be reported.

  Up to approximately 5 years

• Number of participants with ≥1 hepatic AE

  An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Hepatic events of clinical interest (ECIs) include any of the following events if the event is considered not due to disease progression as judged by the investigator: among participants with Baseline ALT \<2 × ULN: ALT ≥5 × ULN; among participants with Baseline ALT ≥2 × ULN: ALT \>3 × the Baseline level; ALT \>500 U/L regardless of baseline level; total bilirubin \>3.0 mg/dL; hepatic decompensation diagnosed clinically (regardless of laboratory values) including new onset clinically detectable ascites requiring intervention for \>3 days, hepatic encephalopathy, or gastrointestinal bleeding suggestive of portal hypertension. The number of participants with a hepatic AE will be reported.

  Up to approximately 5 years

• Number of participants discontinuing study treatment due to an AE

  An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants that discontinue study treatment due to an AE will be reported.

  Up to approximately 5 years

• Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR)

  ORR is defined as the percentage of participants who achieve a confirmed Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters \[SOD\] of target lesions) per RECIST 1.1 adjusted for this study to allow a maximum of 10 target lesions in total and 5 per organ, and assessed by BICR.

  Up to approximately 28 months

Secondary Outcomes (10)

• Duration of Response (DOR) per RECIST 1.1 as assessed by BICR

  Up to approximately 28 months

• Disease Control Rate (DCR) per RECIST 1.1 as assessed by BICR

  Up to approximately 28 months

• Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR

  Up to approximately 28 months

• Time-To-Progression (TTP) per RECIST 1.1 as assessed by BICR

  Up to approximately 28 months

• Overall Survival (OS)

  Up to approximately 28 months

Study Arms (1)

Pembrolizumab/Quavonlimab + Lenvatinib

EXPERIMENTAL

Participants 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.

Biological: Pembrolizumab/Quavonlimab; Drug: Lenvatinib; Biological: Pembrolizumab

Interventions

Pembrolizumab/Quavonlimab BIOLOGICAL

Pembrolizumab/Quavonlimab (400 mg/25 mg) administered via IV infusion Q6W.

Also known as: MK-1308A

Pembrolizumab/Quavonlimab + Lenvatinib

Lenvatinib DRUG

Lenvatinib 12 mg (body weight \[BW\] ≥60 kg) or 8 mg (BW \<60 kg) administered orally every day (QD).

Also known as: MK-7902

Pembrolizumab/Quavonlimab + Lenvatinib

Pembrolizumab BIOLOGICAL

Pembrolizumab (400 mg) administered via IV infusion Q6W, in the event of intolerable toxicity to pembrolizumab/quavonlimab.

Also known as: MK-3475, KEYTRUDA®

Pembrolizumab/Quavonlimab + Lenvatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (40)

City of Hope Comprehensive Cancer Center ( Site 0002)

Duarte, California, 91010, United States

Location

Johns Hopkins Hospital-Sidney Kimmel Comprehensive Cancer Center - GI and Immunology ( Site 0013)

Baltimore, Maryland, 21287, United States

Location

Icahn School of Medicine at Mount Sinai ( Site 0009)

New York, New York, 10029, United States

Location

Oregon Health and Science University ( Site 0006)

Portland, Oregon, 97239, United States

Location

Charleston Oncology ( Site 0003)

Charleston, South Carolina, 29414, United States

Location

Blue Ridge Cancer Care ( Site 0008)

Roanoke, Virginia, 24014, United States

Location

Virginia Mason Medical Center ( Site 0004)

Seattle, Washington, 98101, United States

Location

Anhui Provincial Hospital ( Site 0113)

Hefei, Anhui, 230071, China

Location

Beijing Cancer hospital-Department of Hepato-Pancreato-Biliary Surgery II ( Site 0107)

Beijing, Beijing Municipality, 100142, China

Location

Fuzhou General hospital of Nanjing Military Command-Oncology Department ( Site 0105)

Fuzhou, Fujian, China

Location

Southern Medical University Nanfang Hospital-Liver Cancer Department ( Site 0106)

Guangzhou, Guangdong, 510515, China

Location

Wuhan Union Hospital Cancer Center ( Site 0108)

Wuhan, Hubei, 430022, China

Location

Hunan Cancer Hospital-intervention department ( Site 0109)

Changsha, Hunan, 410013, China

Location

The First Affiliated Hospital of Xian Jiaotong University ward1 depattment of medical oncology ( Sit

Xi'an, Shaanxi, 710061, China

Location

Zhongshan Hospital,Fudan University ( Site 0103)

Shanghai, Shanghai Municipality, 200032, China

Location

Huashan Hospital Affiliated Fudan University-Surgery Department ( Site 0118)

Shanghai, Shanghai Municipality, 200040, China

Location

Humanitas-U.O di Oncologia medica ed Ematologia ( Site 0231)

Rozzano, Milano, 20089, Italy

Location

Ospedale San Raffaele-Oncologia Medica ( Site 0227)

Milan, 20132, Italy

Location

Istituto Nazionale Tumori IRCCS Fondazione Pascale-Department of Abdominal Oncology ( Site 0230)

Napoli, 80131, Italy

Location

National Cancer Center Hospital East ( Site 0153)

Kashiwa, Chiba, 2778577, Japan

Location

Toranomon Hospital Kajigaya ( Site 0154)

Kawasaki, Kanagawa, 213-8587, Japan

Location

Kindai University Hospital- Osakasayama Campus-Department of Gastroenterology and Hepatology ( Site

Sayama, Osaka, 589-8511, Japan

Location

Hiroshima University Hospital ( Site 0156)

Hiroshima, 734-8551, Japan

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Onkologii i Radioterapii ( Site

Warsaw, Masovian Voivodeship, 02-034, Poland

Location

Wojewódzki Szpital im. Św. Ojca Pio w Przemyślu ( Site 0249)

Przemyśl, Podkarpackie Voivodeship, 37-700, Poland

Location

Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0247)

Gdansk, Pomeranian Voivodeship, 80-952, Poland

Location

Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0246)

Koszalin, West Pomeranian Voivodeship, 75-581, Poland

Location

Seoul National University Bundang Hospital-Medical Oncology ( Site 0290)

Seongnam, Kyonggi-do, 13620, South Korea

Location

Samsung Medical Center ( Site 0288)

Seoul, Kyonggi-do, 06351, South Korea

Location

Asan Medical Center ( Site 0289)

Seoul, 05505, South Korea

Location

Hospital Universitario Central de Asturias-Hepatology ( Site 0309)

Oviedo, Principality of Asturias, 33011, Spain

Location

Hospital Universitari Vall d'Hebron-Liver Unit - Department of Internal Medicine ( Site 0310)

Barcelona, 08035, Spain

Location

Hôpitaux Universitaires de Genève (HUG) ( Site 0335)

Geneva, Canton of Geneva, 1211, Switzerland

Location

Cantonal Hospital St.Gallen-Klinik für Gastroenterologie / Hepatologie ( Site 0334)

Sankt Gallen, Canton of St. Gallen, 9007, Switzerland

Location

CHUV (centre hospitalier universitaire vaudois) ( Site 0333)

Lausanne, Canton of Vaud, 1011, Switzerland

Location

UniversitätsSpital Zürich-Gastroenterologie & Hepatologie ( Site 0332)

Zurich, Canton of Zurich, 8091, Switzerland

Location

Inselspital Bern-Universitätsklinik für Viszerale Chirurgie und Medizin ( Site 0331)

Bern, 3010, Switzerland

Location

NATIONAL CHENG-KUNG UNI. HOSP.-Clinical Trial Research Team of Liver Diseases ( Site 0354)

Tainan, 704, Taiwan

Location

National Taiwan University Hospital-Oncology ( Site 0351)

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital-Division of Gastroenterology & Hepatology, Department of Medicine (

Taipei, 112201, Taiwan

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Diabetes Mellitus, Insulin-Dependent, 12; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; lenvatinib

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2021
• First Posted: February 5, 2021
• Study Start: March 16, 2021
• Primary Completion: July 29, 2025
• Study Completion: July 29, 2025
• Last Updated: August 13, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

IT (3); US (7); ES (2); JP (4); CH (5); CN (9); PL (4); KR (3); TW (3)