Pembrolizumab (Keytruda) in Advanced Hepatocellular Carcinoma

NCT02658019 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 20151049
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm phase II trial of Pembrolizumab (Keytruda) in patients with advanced, unresectable hepatocellular carcinoma. The primary objective is to assess its therapeutic efficacy in patients with unresectable hepatocellular carcinoma (HCC).

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular Carcinoma; Advanced Hepatocellular Carcinoma; Unresectable Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (2)

• Disease Control Rate (DCR) in Study Participants

  Disease control rate (DCR) will be calculated per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, as the percentage of patients with best overall response to protocol therapy of either complete response (CR), partial response (PR) or stable disease (SD) that is maintained for at least 8 weeks. Per Response Evaluation Criteria in Sold Tumors Criteria (RECISTv1.1)for target lesions and assessed by MRI or CT: Complete response(CR),Disappearance of all target lesions; Partial response(PR),\>=30% decrease in sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

  8 weeks

• Number of Participants With Treatment-Related Adverse Events

  The safety of Pembrolizumab in HCC patients as measured by the incidence of treatment-related adverse events, including serious adverse events (SAEs), in study participants using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, per physician discretion. The number of participants experiencing toxicity attributed by treating physician as definitely, probably and possibly-related to study treatment will be reported.

  Up to 2 years

Secondary Outcomes (4)

• Progression-Free Survival (PFS)

  Up to 25 months

• Overall Survival (OS)

  Up to 25 months

• Objective Response Rate (ORR)

  Up to 2 years

• Duration of Response (DoR)

  Up to 3 Years

Study Arms (1)

Pembrolizumab in Advanced HCC

EXPERIMENTAL

Patients will be treated in three-week cycles, with intravenous (IV) administration of 200 mg of pembrolizumab on day 1 of each 3-week cycle. Trial therapy will last until withdrawal of consent, disease progression and/or unacceptable toxicity, whichever occurs first.

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Patients will be treated in three-week cycles, with intravenous (IV) administration of 200 mg of pembrolizumab on day 1 of each 3-week cycle.

Also known as: Keytruda, MK-3475

Pembrolizumab in Advanced HCC

Eligibility Criteria

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

You may qualify if:

• Patients must have diagnosis of advanced hepatocellular cancer (HCC) by one of the following:
• Histopathology
• Elevated serum alpha-fetoprotein (AFP) \>400 ng/ml and findings on magnetic resonance imaging (MRI) or computed tomography (CT) scans characteristic of HCC
• Findings on triple phase MRI or CT scans characteristic of HCC in patients with cirrhosis and tumors at least 1 cm or greater, without a curative treatment option (transplant, resection, or ablation).
• Measurable disease as defined by RECIST v1.1 (provided in Section 14.0).
• Radiographic progression on previously treated areas (as defined by RECIST v1.1).
• Subject refusal for sorafenib treatment or intolerance to sorafenib are also allowed (intolerance is defined as ≥ 28 days of sorafenib (not necessarily consecutive) or ≥grade 3 toxicity due to sorafenib which does not resolve with appropriate supportive care).
• Patients should have failed at least one prior systemic therapy regimen which could include sorafenib. Patients may have progressed on sorafenib, been intolerant of, or refused sorafenib. Patients who are documented to refuse systemic chemotherapy or sorafenib are also eligible. No limit to prior systemic therapy. Prior locoregional therapy such as surgery, radiofrequency ablation or transarterial chemoembolization are also allowed, provided that progression has been documented after these therapies, and ≥4 weeks have elapsed since the last therapy; (these will not be counted as systemic therapy).
• Child-Pugh Classification with score ≤ 7 points. See Appendix G for criteria.
• Age ≥ 18 years
• Estimated life expectancy, in the judgement of the Investigator, of at least ≥ 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. See Appendix C.
• Adequate bone marrow function as defined below:
• absolute neutrophil count (ANC) ≥ 1.2 x 10\^9/L,
• platelets (PLT) ≥ 50 x 10\^9/L

You may not qualify if:

• 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.
• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 years prior to the first dose of trial treatment.
• Major surgical procedure within 28 days prior to enrollment. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Any unresolved toxicity \> CTCAE grade 2 despite optimal care/support, from previous anti-cancer therapy, within 28 days prior to first dose of study drug. \[Exceptions: Alopecia and ≤grade 2 neuropathy.\]
• Prior therapy with an anti-Programmed Death (PD)-1, anti-PD-Ligand-(L)-1, or anti-PD-L2 agent.
• Receipt of anti-cancer monoclonal antibody within 4 weeks prior to first dose of study drug.
• Prior treatment with any other chemotherapy, radiotherapy, immunotherapy, or anticancer drug, agent or biologic within 4 weeks prior to first dose of study drug.
• Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
• Receipt of any other investigational agents for their cancer ≤4 weeks of the first dose of study treatment.
• Known history of active Bacillus Tuberculosis (TB).
• Known history of, or any evidence of active, non-infectious pneumonitis or has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Known history of Human Immunodeficiency Virus (HIV), HIV-1/2 antibodies.
• Known hypersensitivity to pembrolizumab or any of its excipients.
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. \[Exception: Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging, for at least 4 weeks prior to the first dose of study drug and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not apply to carcinomatous meningitis which is excluded regardless of clinical stability.\]
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial through 120 days after the last dose of trial treatment.

Sponsors & Collaborators

• Lynn Feun, MD: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

Location

Related Publications (2)

• Feun LG, Li YY, Wu C, Wangpaichitr M, Jones PD, Richman SP, Madrazo B, Kwon D, Garcia-Buitrago M, Martin P, Hosein PJ, Savaraj N. Phase 2 study of pembrolizumab and circulating biomarkers to predict anticancer response in advanced, unresectable hepatocellular carcinoma. Cancer. 2019 Oct 15;125(20):3603-3614. doi: 10.1002/cncr.32339. Epub 2019 Jun 28.

  PMID: 31251403 RESULT

• Zhou X, Cao J, Topatana W, Xie T, Chen T, Hu J, Li S, Juengpanic S, Lu Z, Zhang B, Wang K, Feng X, Shen J, Chen M. Evaluation of PD-L1 as a biomarker for immunotherapy for hepatocellular carcinoma: systematic review and meta-analysis. Immunotherapy. 2023 Apr;15(5):353-365. doi: 10.2217/imt-2022-0168. Epub 2023 Feb 27.

  PMID: 36852452 DERIVED

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

Results Point of Contact

• Title: Lynn G. Feun, MD
• Organization: University of Miami

lfeun@med.miami.edu

305-243-6606

Study Officials

• Lynn Feun, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 14, 2016
• First Posted: January 18, 2016
• Study Start: May 6, 2016
• Primary Completion: November 10, 2019
• Study Completion: December 17, 2019
• Last Updated: November 12, 2020
• Results First Posted: November 12, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)