Longitudinal Immune-phenotyping of HCC Following MK-3475

NCT04224480 | Unknown Phase 1 DMC

• 1 other identifier: NCCS-OTSP-HCC1
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (2)

• Number of subjects with HCC recurrence

  To evaluate the effect of neoadjuvant and adjuvant pembrolizumab on recurrence rate

  2 years after hepatic resection

• Number of CD8+ Ki67+ T cells found in resected tumour from subjects

  To compare the phenotype of immune cells in the tumor microenvironment after tumor resection from recurrence-free verses recurrent subjects receiving pembrolizumab

  Up to 24 months after hepatic resection

Study Arms (1)

Treatment

EXPERIMENTAL

Neoadjuvant treatment will consist of one dose of IV pembrolizumab. Tumor resection will be performed approximately 4 weeks after neoadjuvant pembrolizumab. Adjuvant treatment with pembrolizumab will be administered 4 weeks after the surgery.

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

200mg of intravenous infusion every 3 weeks

Also known as: MK-3475

Treatment

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent for the trial. The subject may also provide consent for donation of tissue to the SingHealth Tissue Repository (STR). However, the subject may participate in the trial without participating in STR.
• Be male or female subject, who is at least 21 years of age on the date of first signed written informed consent
• Have diagnosis of HCC by AASLD imaging criteria or by cytology/histology.
• Have technically resectable HCC, with complete extirpation of HCC at end of surgery by resection +/- intra-operative radiofrequency ablation (RFA) at time of enrolment:
• Without extrahepatic metastases
• Regional lymph nodes (LN) \<2 cm
• Lung lesions \<1 cm
• Without invasion of main portal vein (PV3), or major left and right branches (PV2)
• Future liver remnant of \>40%
• \<5 hepatic lesions in total
• Have tumor larger than 1.5 cm in size
• Demonstrate adequate organ function as defined in Table 3, all screening labs should be performed within 14 days of neoadjuvant treatment initiation.
• Absolute neutrophil count (ANC): ≥1,200/mcL
• Platelets: ≥80,000/ mcL
• Hemoglobin: ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead
• National Medical Research Council (NMRC), Singapore: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

National Cancer Centre Singapore

Singapore, Singapore

Location

Related Publications (2)

• Gao Q, Wang XY, Qiu SJ, Yamato I, Sho M, Nakajima Y, Zhou J, Li BZ, Shi YH, Xiao YS, Xu Y, Fan J. Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res. 2009 Feb 1;15(3):971-9. doi: 10.1158/1078-0432.CCR-08-1608.

  PMID: 19188168 BACKGROUND

• Welker MW, Bechstein WO, Zeuzem S, Trojan J. Recurrent hepatocellular carcinoma after liver transplantation - an emerging clinical challenge. Transpl Int. 2013 Feb;26(2):109-18. doi: 10.1111/j.1432-2277.2012.01562.x. Epub 2012 Sep 21.

  PMID: 22994652 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Han Chong Toh, MD

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2020
• First Posted: January 13, 2020
• Study Start: December 10, 2019
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: January 19, 2024

Record last verified: 2024-01

Locations

SG (1)