Advanced Hepatocellular CarcinomaPhase 2NCT04740307
Safety and Efficacy of Coformulated Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib (E7080/MK-7902) in Advanced Hepatocellular Carcinoma (MK-1308A-004)
A Phase 2 study testing Pembrolizumab/Quavonlimab, Lenvatinib and Pembrolizumab in people with Advanced Hepatocellular Carcinoma, run by Merck Sharp & Dohme LLC at 40 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Hepatocellular Carcinoma
- What is being tested?
- Pembrolizumab/Quavonlimab, Lenvatinib and Pembrolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 116 participants
- Where
- 40 sitesin 9 countries
- Study dates
- 16 Mar 2021to 29 Jul 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- 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.
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- 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.
Who cannot join
- 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])
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- 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
Trial locations and contacts
40 sites in 9 countries.
40 sites in 9 countries
China9 sites
Beijing Cancer hospital-Department of Hepato-Pancreato-Biliary Surgery II ( Site 0107)
Beijing, Beijing Municipality, 100142
Hunan Cancer Hospital-intervention department ( Site 0109)
Changsha, Hunan, 410013
Fuzhou General hospital of Nanjing Military Command-Oncology Department ( Site 0105)
Fuzhou, Fujian
Southern Medical University Nanfang Hospital-Liver Cancer Department ( Site 0106)
Guangzhou, Guangdong, 510515
Anhui Provincial Hospital ( Site 0113)
Hefei, Anhui, 230071
Zhongshan Hospital,Fudan University ( Site 0103)
Shanghai, Shanghai Municipality, 200032
Huashan Hospital Affiliated Fudan University-Surgery Department ( Site 0118)
Shanghai, Shanghai Municipality, 200040
Wuhan Union Hospital Cancer Center ( Site 0108)
Wuhan, Hubei, 430022
The First Affiliated Hospital of Xian Jiaotong University ward1 depattment of medical oncology ( Sit
Xi'an, Shaanxi, 710061
United States7 sites
Johns Hopkins Hospital-Sidney Kimmel Comprehensive Cancer Center - GI and Immunology ( Site 0013)
Baltimore, Maryland, 21287
Charleston Oncology ( Site 0003)
Charleston, South Carolina, 29414
City of Hope Comprehensive Cancer Center ( Site 0002)
Duarte, California, 91010
Icahn School of Medicine at Mount Sinai ( Site 0009)
New York, New York, 10029
Oregon Health and Science University ( Site 0006)
Portland, Oregon, 97239
Blue Ridge Cancer Care ( Site 0008)
Roanoke, Virginia, 24014
Virginia Mason Medical Center ( Site 0004)
Seattle, Washington, 98101
Switzerland5 sites
Inselspital Bern-Universitätsklinik für Viszerale Chirurgie und Medizin ( Site 0331)
Bern, 3010
Hôpitaux Universitaires de Genève (HUG) ( Site 0335)
Geneva, Canton of Geneva, 1211
CHUV (centre hospitalier universitaire vaudois) ( Site 0333)
Lausanne, Canton of Vaud, 1011
Cantonal Hospital St.Gallen-Klinik für Gastroenterologie / Hepatologie ( Site 0334)
Sankt Gallen, Canton of St. Gallen, 9007
UniversitätsSpital Zürich-Gastroenterologie & Hepatologie ( Site 0332)
Zurich, Canton of Zurich, 8091
Japan4 sites
Hiroshima University Hospital ( Site 0156)
Hiroshima, 734-8551
National Cancer Center Hospital East ( Site 0153)
Kashiwa, Chiba, 2778577
Toranomon Hospital Kajigaya ( Site 0154)
Kawasaki, Kanagawa, 213-8587
Kindai University Hospital- Osakasayama Campus-Department of Gastroenterology and Hepatology ( Site
Sayama, Osaka, 589-8511
Poland4 sites
Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0247)
Gdansk, Pomeranian Voivodeship, 80-952
Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0246)
Koszalin, West Pomeranian Voivodeship, 75-581
Wojewódzki Szpital im. Św. Ojca Pio w Przemyślu ( Site 0249)
Przemyśl, Podkarpackie Voivodeship, 37-700
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Onkologii i Radioterapii ( Site
Warsaw, Masovian Voivodeship, 02-034
Italy3 sites
Ospedale San Raffaele-Oncologia Medica ( Site 0227)
Milan, 20132
Istituto Nazionale Tumori IRCCS Fondazione Pascale-Department of Abdominal Oncology ( Site 0230)
Naples, 80131
Humanitas-U.O di Oncologia medica ed Ematologia ( Site 0231)
Rozzano, Milano, 20089
South Korea3 sites
Seoul National University Bundang Hospital-Medical Oncology ( Site 0290)
Seongnam, Kyonggi-do, 13620
Samsung Medical Center ( Site 0288)
Seoul, Kyonggi-do, 06351
Asan Medical Center ( Site 0289)
Seoul, 05505
Taiwan3 sites
NATIONAL CHENG-KUNG UNI. HOSP.-Clinical Trial Research Team of Liver Diseases ( Site 0354)
Tainan, 704
National Taiwan University Hospital-Oncology ( Site 0351)
Taipei, 10002
Taipei Veterans General Hospital-Division of Gastroenterology & Hepatology, Department of Medicine (
Taipei, 112201
Spain2 sites
Hospital Universitari Vall d'Hebron-Liver Unit - Department of Internal Medicine ( Site 0310)
Barcelona, 08035
Hospital Universitario Central de Asturias-Hepatology ( Site 0309)
Oviedo, Principality of Asturias, 33011
About this study
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
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
- Being tested
- Pembrolizumab/Quavonlimab, Lenvatinib, Pembrolizumab
- 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
- Medical subject headings
- Diabetes Mellitus, Insulin-Dependent, 12, Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pembrolizumab/QuavonlimabBiological
Also called MK-1308A
Pembrolizumab/Quavonlimab (400 mg/25 mg) administered via IV infusion Q6W.
LenvatinibDrug
Also called MK-7902
Lenvatinib 12 mg (body weight [BW] ≥60 kg) or 8 mg (BW <60 kg) administered orally every day (QD).
PembrolizumabBiological
Also called MK-3475, KEYTRUDA®
Pembrolizumab (400 mg) administered via IV infusion Q6W, in the event of intolerable toxicity to pembrolizumab/quavonlimab.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Pembrolizumab/Quavonlimab; Drug: Lenvatinib; Biological: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With a Dose-Limiting Toxicity (DLT) in the Safety Lead-in Phase
DLTs were 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; a treatment-related adverse event (AE) causing discontinuation of study intervention during the DLT window; any Grade 5 toxicity.
Measured: 3 weeks
Number of Participants With ≥1 Adverse Event (AE)
An AE was 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 was reported.
Measured: Up to approximately 44 months
Number of Participants With ≥1 Serious Adverse Event (SAE)
An AE was 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 was defined as any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was another important medical event. The number of participants with an SAE was reported.
Measured: Up to approximately 44 months
Number of Participants With ≥1 Immune-related AE (irAE)
An AE was 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 pembrolizumab/quavonlimab exposure may represent an immune-related response. A list of irAEs was pre-specified for the compound of pembrolizumab/quavonlimab. The number of participants with an irAE was reported.
Measured: Up to approximately 44 months
Number of Participants With ≥1 Hepatic AE
An AE was 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) included 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 was reported.
Measured: Up to approximately 44 months
Number of Participants Discontinuing Study Treatment Due to an AE
An AE was 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 discontinued study treatment due to an AE was reported.
Measured: Up to approximately 40 months
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 was 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. The percentage of participants who experienced CR or PR per RECIST 1.1 as assessed BICR was presented.
Measured: Up to approximately 51 months
Secondary outcomes (10)
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
For participants who demonstrated confirmed CR or PR per RECIST 1.1 assessed by BICR, DOR was 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 occurred 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 was 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 was also considered PD. The DOR as assessed using RECIST 1.1 for all participants who experienced a confirmed CR or PR was presented.
Measured: Up to approximately 51 months
Disease Control Rate (DCR) Per RECIST 1.1 as Assessed by BICR
DCR was 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. The percentage of participants who achieved CR, PR, or SD after ≥6 weeks per RECIST 1.1 assessed by BICR was presented.
Measured: Up to approximately 51 months
Progression Free Survival (PFS) Per RECIST 1.1 as Assessed by BICR
PFS was 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 was also considered PD. PFS per RECIST 1.1 as assessed by BICR was reported.
Measured: Up to approximately 51 months
Time-To-Progression (TTP) Per RECIST 1.1 as Assessed by BICR
TTP was 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. TTP per RECIST 1.1 as assessed by BICR was presented.
Measured: Up to approximately 51 months
Overall Survival (OS)
OS was defined as the time from the first dose of study intervention to death due to any cause.
Measured: Up to approximately 51 months
ORR Per Modified RECIST (mRECIST) as Assessed by BICR
ORR was 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. The percentage of participants who experienced CR or PR per mRECIST as assessed BICR was presented.
Measured: Up to approximately 51 months
DOR Per mRECIST as Assessed by BICR
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. The DOR as assessed using mRECIST for all participants who experienced a confirmed CR or PR was presented.
Measured: Up to approximately 51 months
DCR Per mRECIST as Assessed by BICR
DCR was 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. The percentage of participants who achieved CR, PR, or SD after ≥6 weeks per mRECIST assessed by BICR was presented.
Measured: Up to approximately 51 months
PFS Per mRECIST as Assessed by BICR
PFS was 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. PFS per mRECIST as assessed by BICR was reported.
Measured: Up to approximately 51 months
TTP Per mRECIST as Assessed by BICR
TTP was 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. TTP per mRECIST as assessed by BICR was presented.
Measured: Up to approximately 51 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2021
- Study start16 Mar 2021
- Primary completion29 Jul 2025
- Study completion29 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Advanced Hepatocellular CarcinomaStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 116 participants (actual)
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
- NCT04740307
- Sponsor's protocol ID
- 1308A-004
- Other IDs
- MK-1308A-004, jRCT2061210033, 2023-505698-34-00, U1111-1292-3158, 2020-004490-52, 2023
- Status last verified
- Jun 2026
- First submitted
- 2 Feb 2021
- Last updated
- 30 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04740307
- Acronym / sponsor ID
- 1308A-004
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 116 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 16 Mar 2021 (actual)
- Primary completion
- 29 Jul 2025 (actual)
- Study completion
- 29 Jul 2025 (actual)
- First posted
- 5 Feb 2021 (actual)
- Results
- Posted 23 Jun 2026
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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab/Quavonlimab + Lenvatinib | Experimental | Biological: Pembrolizumab/Quavonlimab, Drug: Lenvatinib, Biological: PembrolizumabParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (31 listed)
- 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
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 |
|---|---|---|
| Pembrolizumab/QuavonlimabAlso: MK-1308APembrolizumab/Quavonlimab (400 mg/25 mg) administered via IV infusion Q6W. | Biological | Pembrolizumab/Quavonlimab + Lenvatinib |
| LenvatinibAlso: MK-7902Lenvatinib 12 mg (body weight [BW] ≥60 kg) or 8 mg (BW <60 kg) administered orally every day (QD). | Drug | Pembrolizumab/Quavonlimab + Lenvatinib |
| PembrolizumabAlso: MK-3475, KEYTRUDA®Pembrolizumab (400 mg) administered via IV infusion Q6W, in the event of intolerable toxicity to pembrolizumab/quavonlimab. | Biological | Pembrolizumab/Quavonlimab + Lenvatinib |
Primary outcome
Number of Participants With a Dose-Limiting Toxicity (DLT) in the Safety Lead-in Phase
Time frame: 3 weeks
DLTs were 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; a treatment-related adverse event (AE) causing discontinuation of study intervention during the DLT window; any Grade 5 toxicity.
Number of Participants With ≥1 Adverse Event (AE)
Time frame: Up to approximately 44 months
An AE was 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 was reported.
Number of Participants With ≥1 Serious Adverse Event (SAE)
Time frame: Up to approximately 44 months
An AE was 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 was defined as any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was another important medical event. The number of participants with an SAE was reported.
Number of Participants With ≥1 Immune-related AE (irAE)
Time frame: Up to approximately 44 months
An AE was 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 pembrolizumab/quavonlimab exposure may represent an immune-related response. A list of irAEs was pre-specified for the compound of pembrolizumab/quavonlimab. The number of participants with an irAE was reported.
Number of Participants With ≥1 Hepatic AE
Time frame: Up to approximately 44 months
An AE was 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) included 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 was reported.
Number of Participants Discontinuing Study Treatment Due to an AE
Time frame: Up to approximately 40 months
An AE was 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 discontinued study treatment due to an AE was reported.
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)
Time frame: Up to approximately 51 months
ORR was 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. The percentage of participants who experienced CR or PR per RECIST 1.1 as assessed BICR was presented.
10 secondary outcomes
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
Time frame: Up to approximately 51 months
Disease Control Rate (DCR) Per RECIST 1.1 as Assessed by BICR
Time frame: Up to approximately 51 months
Progression Free Survival (PFS) Per RECIST 1.1 as Assessed by BICR
Time frame: Up to approximately 51 months
Time-To-Progression (TTP) Per RECIST 1.1 as Assessed by BICR
Time frame: Up to approximately 51 months
Overall Survival (OS)
Time frame: Up to approximately 51 months
ORR Per Modified RECIST (mRECIST) as Assessed by BICR
Time frame: Up to approximately 51 months
DOR Per mRECIST as Assessed by BICR
Time frame: Up to approximately 51 months
DCR Per mRECIST as Assessed by BICR
Time frame: Up to approximately 51 months
PFS Per mRECIST as Assessed by BICR
Time frame: Up to approximately 51 months
TTP Per mRECIST as Assessed by BICR
Time frame: Up to approximately 51 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Plain Language SummaryLink 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
40 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab/Quavonlimab, Lenvatinib and Pembrolizumab in people with Advanced Hepatocellular Carcinoma, run by Merck Sharp & Dohme LLC at 40 sites in 9 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 9 inclusion and 31 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: finished, as of the sponsor's last update on 30 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in China, United States, Switzerland, Japan, Poland and 4 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?
Yes. Results are posted in the registry (first posted 23 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With a Dose-Limiting Toxicity (DLT) in the Safety Lead-in Phase (time frame: 3 weeks). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Jun 2026.