A Phase 2 Study of Pembrolizumab (MK-3475) in subjects with Advanced Hepatocellular Carcinoma

Phase 1

• Conditions: Hepatocellular Carcinoma; MedDRA version: 21.0Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectableSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-004566-28-IT
• Lead Sponsor: MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-22
• Last Update Posted: 2 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

Subjects must:
1. Provide informed consent.
2. Be > or = 18 years of age.
3. Have histologically or cytologically confirmed diagnosis of HCC based on pathology report (Cohort 1), or have an HCC diagnosis confirmed by radiology, histology, or cytology (Cohort 2).
4. Have a life expectancy greater than 3 months
5. Have 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.
6. Have a Child-Pugh A liver score.
7. Have measurable disease based on RECIST 1.1 as confirmed by the blinded central imaging vendor.
8. Have ECOG Performance Scale of 0 or 1.
9. Have documented objective radiographic progression after stopping treatment with sorafenib or else intolerance to sorafenib (Cohort 1 only).
10. Be untreated for chronic HCV or 4 weeks have passed between completion of HCV therapy and start of study drug.
11. Demonstrate adequate organ function.
12. Have negative pregnancy test for females of child bearing potential prior to starting study and male and female subjects of childbearing potential must be willing to use an adequate method of contraception.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

The subject will be excluded from participating in the trial if the subject:
1. Is currently participating and receiving study therapy or has participated in an investigational agent and received study therapy, herbal/complementary oral or IV medicine, or used an investigational device within 4 weeks of the first dose of treatment.
2. Has received sorafenib within 14 days of first dose of study medication (Cohort 1 only).
3. Has had esophageal or gastric variceal bleeding within the last 6 months.
4. Has clinically apparent ascites on physical examination, (ascites detectable on imaging studies only IS allowed).
5. Has portal vein invasion at the main portal (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging.
6. Has had encephalopathy in the last 6 months.
7. Had a solid organ or hematologic transplant.
8. Had prior systemic therapy for HCC other than sorafenib, or intercurrent local therapy to the liver tumor between sorafenib and study drug (Cohort 1), or had prior systemic therapy in the advanced disease setting (Cohort 2).
9. Has active autoimmune disease that required treatment in the past two years.
10. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
11. Has received locoregional therapy to liver or major surgery to liver or other site within 6 weeks in Cohort 1 and 4 weeks in Cohort 2 prior to the first dose of study drug.
12. Has a diagnosed additional malignancy within 5 years for Cohort 1 and 3 years for Cohort 2 prior to first dose of trial treatment with some exceptions.
13. Has radiographically detectable central nervous system (CNS) metastases and/or carcinomatous meningitis.
14. Has a known history of, or evidence of, interstitial lung disease or active non-infectious pneumonitis.
15. Has an active infection requiring systemic therapy.
16. Has a known severe hypersensitivity (>=Grade 3) to pembrolizumab, its active substance and/or any of its excipients.
17. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator, including dialysis.
18. Has known psychiatric or substance abuse disorders.
19. Is pregnant or breastfeeding.
20. Has received prior immunotherapy or previously participated in Merck pembrolizumab clinical trials.
21. Has a known history of human immunodeficiency virus (HIV).
22. Has untreated active Hepatitis B.
23. Has dual infection with HBV/HCV or other hepatitis combinations at study entry (Cohort 1 only); has dual active HBV infection (HBsAg (+) and/or detectable HBV DNA) and HCV infection (detectable HCV RNA) at study entry (Cohort 2 only).
24. Has received a live vaccine within 30 days of planned start of study therapy, with exception for killed virus vaccines used for seasonal influenza vaccines.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To estimate the ORR, per RECIST 1.1 assessed by central imaging vendor. <br>;Secondary Objective: 1. Objective: To evaluate the duration of response (DOR), disease control rate (DCR), time to progression (TTP), and progression-free survival (PFS) per RECIST 1.1 assessed by central imaging vendor, and OS. <br>2. Objective: To determine the safety and tolerability of pembrolizumab monotherapy.<br>;Primary end point(s): Overall Response Rate (ORR) will be used as the primary endpoint per RECIST 1.1 criteria as assessed by the central imaging vendor.;Timepoint(s) of evaluation of this end point: For Cohort 1 only, an early interim analysis of the safety and efficacy data will be performed for the first 20 patients enrolled; a final analysis will be done at end of study.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The secondary efficacy objectives of this study are to evaluate DOR, and determine the safety and tolerability of pembrolizumab in subjects with HCC. DCR, TTP, and PFS per RECIST 1.1 will also be assessed by the<br>central imaging vendor; and OS will also be examined.;Timepoint(s) of evaluation of this end point: These end points will be evaluated at end of study.