Longitudinal Immune-phenotyping of HCC Following MK-3475

# NCT04224480 Trial phase: 1 Study type: immunotherapy, observational

Study Start Date

December, 2019

Scientific Title

Longitudinal Immune-phenotyping of Surgically Resected HCC Following Neoadjuvant and Adjuvant Treatment With MK-3475


The study comprises a main study of pembro-treated HCC patients and a sub-study of untreated HCC patients. In the main study, patients will be treated with pembrolizumab as neoadjuvant treatment approximately 4 weeks prior scheduled surgery. Adjuvant treatment with pembrolizumab with commence at approximately 4 weeks post-surgery for up to 12 months. Subjects will be followed up for a further 12 months after end of treatment for recurrence and survival. The sub-study is a tumour sample collection study which will provide pre-treatment immune microenvironment data from up to 15 pairs of HCC/adjuvant liver tissue samples. Translational analyses performed for liver tissue samples in the sub-study will be harmonized with the analyses on liver tissue samples collected in the main study.

- 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. The use of physiologic doses of corticosteroids may be approved after consultation with the Protocol Chairperson. Physiologic dose of corticosteroid is defined as ≤ 10 mg/day prednisolone or equivalent.

- Has macrovascular invasion and distant metastases. Definition of metastases includes lymph nodes (LN) ≥ 2 cm in widest diameter and lung lesions ≥ 1 cm in widest diameter).

- Has tumor thrombus involvement in main portal vein (PV3), or major left and right branches (PV2) on pre-operative imaging.

- Has a recurrent HCC < 24 months after previous resection.

- Has had major surgery to any site within 4 weeks prior to the first dose of study drug.

- Has future liver remnant ≤ 40%.

- Has more than 5 lesions in total.

- Has encephalopathy.

- Has history of allergic disease or reactions likely to be exacerbated by any component of pembrolizumab.

- Has had a solid organ or hematologic transplant.

- Has had untreated esophageal or gastric variceal bleeding within the last 6 months.

- Has clinically apparent ascites on physical examination.

- Has had prior anti-cancer treatment for HCC, except for complete ablation of HCC by liver resection and/or RFA at least 24 months prior to current HCC diagnosis. Anti-cancer treatment includes but is not limited to loco-regional therapy (e.g. TACE, radiotherapy, immunotherapy, chemotherapy or neoadjuvant therapy).

- Has previous or concomitant malignancies at other sites, except effectively treated non-melanoma carcinoma of the skin or in situ cervical cancer or effectively treated malignancy that has been in remission for more than 5 years and is highly likely to have been cured.

- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

- Has known history of, or any evidence of active, (non-infectious) pneumonitis that required steroids or current pneumonitis.

- Has uncontrolled congestive heart failure or hypertension, unstable heart disease (coronary artery disease or myocardial infarction) or any uncontrolled arrhythmia at the time of enrollment into study.

- 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.

- Has known psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with trial procedures.

- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.

- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or if the subject has previously participated in Merck pembrolizumab clinical trials

- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

- Has received a live vaccine within 30 days of planned start of study therapy.

- Is currently participating, or has participated, in a study of an investigational agent and received study therapy, herbal/complementary oral or IV medicine, or used an investigation device within 4 weeks of the first dose of treatment. Subjects must also have recovered from associated therapy (i.e. to Grade ≤ 1 or baseline) and from AEs due to any prior therapy.

- Has had a minor surgery ≤ 7 days prior to the first dose of study treatment (Cycle 1, Day 1).

- Has an active infection requiring systemic therapy.

- Has dual active HBV infection [HBsAg (+) and/or detectable HBV DNA] and HCV infection [anti-HCV Ab (+) and detectable HCV RNA] at study entry.

Study Design

Primary purpose: Treatment , Allocation: N/A , Intervention model: Single Group Assignment , Masking: None (Open Label)


Hepatocellular Carcinoma


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