Phase 3 Study of Lenvatinib (E7080/MK-7902) plus Pembrolizumab (MK- 3475) for First-line Therapy of Advanced Hepatocellular Carcinoma

Phase 1

Conditions: Advanced hepatocellular carcinoma
Therapeutic area: Diseases [C] - Cancer [C04]
MedDRA version: 20.0Level: PTClassification code 10073071Term: Hepatocellular carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Registration Number: EUCTR2018-002983-26-PL

Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 750

Inclusion Criteria

1. Have a HCC diagnosis confirmed by radiology, histology, or cytology (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible)
2. Have 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
3. Have a Child-Pugh class A liver score within 7 days prior to first dose of study intervention
4. Have a predicted life expectancy of >3 months
5. Have at least one measurable HCC lesion based on RECIST 1.1 as confirmed by the BICR vendor
6. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 within 7 days prior to first dose of study intervention
7. Participant is male or female
8. Participant is =18 years of age, at the time of signing the informed consent
9. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 30 days after the last dose of lenvatinib:
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
OR
• Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause)
• Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Please note that 30 days after lenvatinib is stopped, if the participant is on pembrolizumab/placebo only, no male contraception measures are needed.
10. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
- Is not a woman of childbearing potential (WOCBP)
OR
- Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days post pembrolizumab/placebo or 30 days post lenvatinib, whichever occurs last. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention.
-If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
11. The participant (or legally acceptable representative if applicable) provides written informed consent/assent for the study
12. Participants with past or ongoing HCV infection will be eligible for the study. The treated participants must have completed their treatment at least 1 month prior to starting study intervention
13. Participants with controlled hepatitis B will be eligible as long as they meet the following criteria:
a) Antiviral therapy for HBV must be given for at least 4 weeks and HBV viral load must be less than 100 IU/mL prior to first dose of study drug. Participants on active HBV therapy with viral loads under 100 IU/mL should stay on the same therapy throughout study treatment
b) Participants who are positive for anti-hepatitis B core antibody HBc, negative for hepatitis B surface antigen (HBsAg), and negative or positive for anti-hepatitis B surface antibody (HBs), and who ha

Exclusion Criteria

1.Has had esophageal or gastric variceal bleeding within the last 6 months. All participants will be screened for esophageal varices unless such screening has been performed in the past 12 months before first dose of treatment
2.Bleeding or thrombotic disorders or use of factor X inhibitors or anticoagulants requiring therapeutic international normalized ratio (INR) monitoring. Treatment with low molecular weight heparin is permitted.
3.Has clinically apparent ascites on physical examination that is not controlled with medication
4.Portal vein invasion (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging.
5.Has had clinically diagnosed hepatic encephalopathy in the last 6 months unresponsive to therapy within 3 days. Participants on rifaximin or lactulose to control their hepatic encephalopathy are not allowed
6.Has medical contraindications that preclude all forms of contrast enhanced imaging(CT or MRI)
7.Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
8.Has a preexisting Grade =3 gastrointestinal or non-gastrointestinal fistula
9.Clinically significant hemoptysis from any source or tumor bleeding within 2 weeks prior to the first dose of study drug
10.Has significant cardiovascular impairment within 12 months of the first dose of study intervention such as history of congestive heart failure greater than New York Heart Association Class II, unstable angina, myocardial infarction or cerebrovascular accident stroke, or cardiac arrhythmia associated with hemodynamic instability
11.Has had major surgery to the liver within 4 weeks prior to the first dose of study intervention
12.Has had a minor surgery within 7 days prior to the first dose of study intervention (Cycle1 Day1)
13.Has serious nonhealing wound, ulcer, or bone fracture
14.Has received any systemic chemotherapy, including anti-VEGF therapy, or any systemic investigational anticancer agents for advanced/unresectable HCC
15.Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PDL2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
16.Has received locoregional therapy to liver within 4 weeks prior to the first dose of study intervention
17.Has received prior radiotherapy to a non-liver region within 2 weeks of start of study intervention
18.Has received a live vaccine within 30 days prior to the first dose of study intervention
19.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
20.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
21.Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
22.Has a known history of, or any evidence of, CNS metastases and/or carcinomatous meningitis as assessed by local site investigator
23.Has severe hypersensitivity (=Grade 3) to study intervention and/or any of their excipients
24.Has an active autoimmune disease that has required systemic treatment in past 2 years
25.Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
26.Participants with proteinuria >1+ on urine dipstick testing will undergo 24-hour urine collection for qu

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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