Clinical trial NCT04740307: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
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
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2021-02-05
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of participants with a Dose-Limiting Toxicity (DLT) in the Safety Lead-in Phase
timeFrame: Cycle 1 (Up to approximately 3 weeks)
measure: Number of participants with ≥1 adverse event (AE)
timeFrame: Up to approximately 5 years
measure: Number of participants with ≥1 serious adverse event (SAE)
timeFrame: Up to approximately 5 years
measure: Number of participants with ≥1 immune-related AE (irAE)
timeFrame: Up to approximately 5 years
measure: Number of participants with ≥1 hepatic AE
timeFrame: Up to approximately 5 years
measure: Number of participants discontinuing study treatment due to an AE
timeFrame: Up to approximately 5 years
measure: 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)
timeFrame: Up to approximately 28 months
Secondary outcomes:
measure: Duration of Response (DOR) per RECIST 1.1 as assessed by BICR
timeFrame: Up to approximately 28 months
measure: Disease Control Rate (DCR) per RECIST 1.1 as assessed by BICR
timeFrame: Up to approximately 28 months
measure: Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR
timeFrame: Up to approximately 28 months
measure: Time-To-Progression (TTP) per RECIST 1.1 as assessed by BICR
timeFrame: Up to approximately 28 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 28 months
measure: ORR per modified RECIST (mRECIST) as assessed by BICR
timeFrame: Up to approximately 28 months
measure: DOR per mRECIST as assessed by BICR
timeFrame: Up to approximately 28 months
measure: DCR per mRECIST as assessed by BICR
timeFrame: Up to approximately 28 months
measure: PFS per mRECIST as assessed by BICR
timeFrame: Up to approximately 28 months
measure: TTP per mRECIST as assessed by BICR
timeFrame: Up to approximately 28 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center ( Site 0002)
state: California
city: Baltimore
country: United States
facility: Johns Hopkins Hospital-Sidney Kimmel Comprehensive Cancer Center - GI and Immunology ( Site 0013)
state: Maryland
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai ( Site 0009)
state: New York
city: Portland
country: United States
facility: Oregon Health and Science University ( Site 0006)
state: Oregon
city: Charleston
country: United States
facility: Charleston Oncology ( Site 0003)
state: South Carolina
city: Roanoke
country: United States
facility: Blue Ridge Cancer Care ( Site 0008)
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center ( Site 0004)
state: Washington
city: Hefei
country: China
facility: Anhui Provincial Hospital ( Site 0113)
state: Anhui
city: Beijing
country: China
facility: Beijing Cancer hospital-Department of Hepato-Pancreato-Biliary Surgery II ( Site 0107)
state: Beijing
city: Fuzhou
country: China
facility: Fuzhou General hospital of Nanjing Military Command-Oncology Department ( Site 0105)
state: Fujian
city: Guangzhou
country: China
facility: Southern Medical University Nanfang Hospital-Liver Cancer Department ( Site 0106)
state: Guangdong
city: Wuhan
country: China
facility: Wuhan Union Hospital Cancer Center ( Site 0108)
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital-intervention department ( Site 0109)
state: Hunan
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xian Jiaotong University ward1 depattment of medical oncology ( Sit
state: Shaanxi
city: Shanghai
country: China
facility: Zhongshan Hospital,Fudan University ( Site 0103)
state: Shanghai
city: Shanghai
country: China
facility: Huashan Hospital Affiliated Fudan University-Surgery Department ( Site 0118)
state: Shanghai
city: Rozzano
country: Italy
facility: Humanitas-U.O di Oncologia medica ed Ematologia ( Site 0231)
state: Milano
city: Milano
country: Italy
facility: Ospedale San Raffaele-Oncologia Medica ( Site 0227)
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Pascale-Department of Abdominal Oncology ( Site 0230)
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East ( Site 0153)
state: Chiba
city: Kawasaki
country: Japan
facility: Toranomon Hospital Kajigaya ( Site 0154)
state: Kanagawa
city: Osakasayama
country: Japan
facility: Kindai University Hospital- Osakasayama Campus-Department of Gastroenterology and Hepatology ( Site
state: Osaka
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital ( Site 0156)
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital-Medical Oncology ( Site 0290)
state: Kyonggi-do
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 0288)
state: Kyonggi-do
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center ( Site 0289)
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Onkologii i Radioterapii ( Site
state: Mazowieckie
city: Przemysl
country: Poland
facility: Wojewódzki Szpital im. Św. Ojca Pio w Przemyślu ( Site 0249)
state: Podkarpackie
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0247)
state: Pomorskie
city: Koszalin
country: Poland
facility: Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0246)
state: Zachodniopomorskie
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias-Hepatology ( Site 0309)
state: Asturias
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron-Liver Unit - Department of Internal Medicine ( Site 0310)
city: Genève
country: Switzerland
facility: Hôpitaux Universitaires de Genève (HUG) ( Site 0335)
state: Geneve
city: St.Gallen
country: Switzerland
facility: Cantonal Hospital St.Gallen-Klinik für Gastroenterologie / Hepatologie ( Site 0334)
state: Sankt Gallen
city: Lausanne
country: Switzerland
facility: CHUV (centre hospitalier universitaire vaudois) ( Site 0333)
state: Vaud
city: Zürich
country: Switzerland
facility: UniversitätsSpital Zürich-Gastroenterologie & Hepatologie ( Site 0332)
state: Zurich
city: Berne
country: Switzerland
facility: Inselspital Bern-Universitätsklinik für Viszerale Chirurgie und Medizin ( Site 0331)
city: Tainan
country: Taiwan
facility: NATIONAL CHENG-KUNG UNI. HOSP.-Clinical Trial Research Team of Liver Diseases ( Site 0354)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital-Oncology ( Site 0351)
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital-Division of Gastroenterology & Hepatology, Department of Medicine (
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: