Phase 1 Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of H3B-6527 in Participants With Advanced Hepatocellular Carcinoma

January 27, 2023 updated by: H3 Biomedicine Inc.

An Open-Label Multicenter Phase 1 Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of H3B-6527 in Subjects With Advanced Hepatocellular Carcinoma

The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of H3B-6527, and to assess the safety, tolerability and pharmacokinetics of H3B-6527.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
128

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Gent, Belgium, 9000
        • Universitair Ziekenhuis Gent
    • Brussels
      • Woluwe-Saint-Lambert, Brussels, Belgium, 1200
        • UCL Cliniques universitaires Saint-Luc
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G IZ2
        • Cross Cancer Institute
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Jurvanski Cancer Center
  • France
      • Bordeaux, France, 33076
        • Institut Bergonie
      • Lille, France, 59000
        • Centre Oscar Lambret
      • Pessac, France, 33604
        • Hôpital Haut-Lévêque - CHU de Bordeaux
      • Rennes, France, 35042
        • Centre Eugene Marquis
  • Italy
      • Meldola, Italy, 47014
        • IRCCS Istituto Scientifico Romagnolo per lo studio e la cura dei tumori - U.O. di Oncologia Medica
      • Milano, Italy, 20132
        • IRCCS Ospedale San Raffaele S.r.l. - PPDS
      • Modena, Italy, 41124
        • Azienda Ospedaliero Universitaria - Policlinico di Modena
  • Korea, Republic of
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center
  • Russian Federation
      • Moscow, Russian Federation, 115478
        • Russian Oncology Research Center n a N N Blokhin
      • Omsk, Russian Federation, 644046
        • Omsk Regional Oncology Center
      • Saint Petersburg, Russian Federation, 198255
        • City Clinical Oncology Dispensary
      • Saint Petersburg, Russian Federation, 195271
        • Railway Clinical Hospital JSC RZhD
    • Altay, Re
      • Barnaul, Altay, Re, Russian Federation, 656045
        • Altay Regional Oncology Center
  • Singapore
      • Singapore, Singapore, 119074
        • National University Cancer Insitute
  • Spain
      • Badajoz, Spain, 06080
        • Hospital Universitario de Badajoz
      • Barcelona, Spain, 8035
        • Hospital Universitario Vall d'Hebron
      • Madrid, Spain, 28050
        • Hospital Universitario HM Sanchinarro
      • Madrid, Spain, 28007
        • General Universitario Gregorio Marañon
      • Madrid, Spain, 28040
        • START Madrid FJD, Hospital Universitario Fundacion Jimenez Diaz
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocío
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • Hospital Universitario Marqués de Valdecilla
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Clinica Universidad de Navarra
  • Taiwan
      • Taichung, Taiwan, 40705
        • Taichung Veterans General Hospital
      • Tainan, Taiwan, 704
        • National Cheng Kung University Hospital
  • United Kingdom
      • London, United Kingdom, W1G 6AD
        • Sarah Cannon Research Institute UK - SCRI - PPDS
  • United States
    • California
      • Los Angeles, California, United States, 90033
        • USC/Norris Comprehensive Cancer Center
      • Newport Beach, California, United States, 92663
        • Hoag Memorial Hospital Presbyterian
      • Orange, California, United States, 92868-3201
        • UC Irvine Medical Center
      • Santa Monica, California, United States, 90404
        • UCLA Medical Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown Unversity Lombardi Comprehensive Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Unversity
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Barbara Ann Karmanos Cancer Institute
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • John Theurer Cancer Center at Hackensack University Medical Center
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Cancer Center
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati Cancer Institute
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylsvania - Perelman Cancer Center for Advanced Medicine
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center
      • Dallas, Texas, United States, 75390
        • Simmons Comprehensive Cancer Center
    • Virginia
      • Richmond, Virginia, United States, 23249
        • McGuire VA Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion criteria:

  1. Participants with hepatocellular carcinoma.
  2. Must have had at least one prior standard-of-care therapy, unless contraindicated.
  3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  4. Must be willing to undergo a biopsy up to 8 weeks before administration of H3B-6527 on Cycle 1 Day 1 for part 2 (dose expansion).
  5. Adequate bone marrow and organ function.

Exclusion criteria:

  1. Uncontrolled significant active infections, except hepatitis B virus (HBV) or hepatitis C virus (HCV).
  2. Known human immunodeficiency virus infection.
  3. Presence of gastric or esophageal varices requiring active treatment.
  4. Previous treatment with a selective FGF19-FGFR4 targeted therapy.
  5. Females of childbearing potential, or males who have not had a successful vasectomy, who are unable or unwilling to follow adequate contraceptive measures.
  6. Hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: H3B-6527 (escalation and expansion)
Hepatocellular Carcinoma
Drug: H3B-6527
H3B-6527 by mouth once or twice daily at specified doses.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Part 1, Dose Escalation Phase: Number of Participants With Dose-limiting Toxicities (DLTs) Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03
Time Frame: Cycle 1 (Cycle length = 21 days)
DLTs were defined as any of the following toxicities: Hematology, gastrointestinal, renal, hepatic or nonhematologic toxicities occurring during Cycle 1 in Dose Escalation Phase only and judged by the investigator as related to study drug. This included any Grade 4: neutropenia that does not resolve to Grade less than or equal to (<=) 2 within 7 days, thrombocytopenia, anemia of any duration, diarrhea and/or vomiting irrespective of prophylaxis or appropriate treatment; Grade 3: thrombocytopenia requiring transfusion, thrombocytopenia and clinically significant bleeding, anemia if transfused or if lasting for more than 7 days, nausea, vomiting and/or diarrhea lasting more than 72 hours despite the use of optimal anti-emetic/antidiarrheal treatment, bilirubin, fatigue lasting less than 1 week, elevations in biochemistry laboratory values without associated clinical symptoms that last for <=7 days; Grade greater than or equal to (>=) 3 serum creatinine.
Cycle 1 (Cycle length = 21 days)
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: From the first dose of study drug up to approximately 36.7 months
A TEAE was defined as an adverse event (AE) that emerges during treatment, having been absent at pretreatment (Baseline) or reemerges during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsens in severity during treatment relative to the pretreatment state, when the AE was continuous. An SAE was any untoward medical occurrence that at any dose: Resulted in death, was life-threatening (that is, the participant was at immediate risk of death from the AE as it occurred; this does not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug).
From the first dose of study drug up to approximately 36.7 months
Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters
Time Frame: From baseline up to approximately 36.7 months
Laboratory assessment included hematology, coagulation, clinical chemistry, and urinalysis parameters.
From baseline up to approximately 36.7 months
Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters
Time Frame: From baseline up to approximately 36.7 months
From baseline up to approximately 36.7 months
Number of Participants With Clinically Significant Change From Baseline in Vital Sign Parameters
Time Frame: From baseline up to approximately 36.7 months
From baseline up to approximately 36.7 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527
Time Frame: Part 1, Cycle 1 Day 1 and Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing); Part 2, Cycle 1 Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing) (Cycle 1 length = 21 days)
Part 1, Cycle 1 Day 1 and Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing); Part 2, Cycle 1 Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing) (Cycle 1 length = 21 days)
Maximum Observed Plasma Concentration (Cmax) of H3B-6527
Time Frame: Part 1, Cycle 1 Day 1 and Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing); Part 2, Cycle 1 Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing) (Cycle 1 length = 21 days)
Part 1, Cycle 1 Day 1 and Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing); Part 2, Cycle 1 Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing) (Cycle 1 length = 21 days)
Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527
Time Frame: Part 1, Cycle 1 Day 1 and Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing); Part 2, Cycle 1 Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing) (Cycle 1 length = 21 days)
Part 1, Cycle 1 Day 1 and Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing); Part 2, Cycle 1 Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing) (Cycle 1 length = 21 days)
Part 2, Dose Expansion Phase: Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1
Time Frame: From the first dose date until disease progression/recurrence or up to approximately 36.7 months
ORR was defined as the percentage of participants achieving a best overall confirmed response of partial response (PR) or complete response (CR) (PR + CR), from the first dose date until disease progression/recurrence. Responses (PR or CR) were confirmed no less than 4 weeks after the initial response. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in the short axis to less than 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The tumor assessment was done using number of lesions based on modified RECIST v1.1 for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ.
From the first dose date until disease progression/recurrence or up to approximately 36.7 months
Part 2, Dose Expansion Phase: Duration of Response (DOR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1
Time Frame: From the date of first documented CR or PR up to approximately 36.7 months
DOR was defined as the time from the date of first documented CR or PR based on modified RECIST v1.1 until the first documentation of disease progression (PD) as determined by the investigator or death, whichever comes first. CR was defined as the disappearance of all target lesions and non-target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of long diameter (LD) of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).
From the date of first documented CR or PR up to approximately 36.7 months
Part 2, Dose Expansion Phase: Progression-free Survival (PFS) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1
Time Frame: From the first dose date to the date of the first documentation of PD as determined by the investigator or death (whichever occurs first) up to approximately 36.7 months
PFS was defined as the time from the first dose date to the date of the first documentation of PD as determined by the investigator or death (whichever occurs first). PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).
From the first dose date to the date of the first documentation of PD as determined by the investigator or death (whichever occurs first) up to approximately 36.7 months
Part 2, Dose Expansion Phase: Overall Survival (OS)
Time Frame: From the date of first dose of study drug until date of death from any cause (up to approximately 36.7 months)
OS was defined as the time from the first dose date to the date of death. OS was assessed using Kaplan-Meier method. The time of death was censored for participants who were without death information at the time of OS analysis.
From the date of first dose of study drug until date of death from any cause (up to approximately 36.7 months)
Part 2, Dose Expansion Phase: Time to Response (TTR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1
Time Frame: From date of first dose of study drug until CR or PR (up to approximately 36.7 months)
TTR was defined as the time from the first dose date to the date of first documented CR/PR. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in the short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
From date of first dose of study drug until CR or PR (up to approximately 36.7 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
H3 Biomedicine Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Eisai Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 28, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 23, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 23, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 13, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 13, 2016

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 15, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 13, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 27, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • H3B-6527-G000-101
  • 2016-001915-19 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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