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

NCT02834780 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: H3B-6527-G000-1012016-001915-19
• Study Type: interventional
• Target: 128
• Locations: 11 countries
• Sites: 44

Brief Summary

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.

Conditions

Advanced Hepatocellular Carcinoma; Hepatocellular Carcinoma; Liver Cancer; Liver Neoplasms; Hepatic Cancer; Hepatic Carcinoma

Keywords

Advanced Hepatocellular Carcinoma; H3B-6527; Fibroblast growth factor receptor 4 (FGFR4); Fibroblast growth factor 19 (FGF19)

Outcome Measures

Primary Outcomes (5)

• 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

  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)

  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

  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

  From baseline up to approximately 36.7 months

• Number of Participants With Clinically Significant Change From Baseline in Vital Sign Parameters

  From baseline up to approximately 36.7 months

Secondary Outcomes (8)

• Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527

  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

  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

  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

  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

  From the date of first documented CR or PR up to approximately 36.7 months

Study Arms (1)

H3B-6527 (escalation and expansion)

EXPERIMENTAL

Hepatocellular Carcinoma

Drug: H3B-6527

Interventions

H3B-6527 DRUG

H3B-6527 by mouth once or twice daily at specified doses.

H3B-6527 (escalation and expansion)

Eligibility Criteria

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

You may qualify if:

• Participants with hepatocellular carcinoma.
• Must have had at least one prior standard-of-care therapy, unless contraindicated.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• 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).
• Adequate bone marrow and organ function.

You may not qualify if:

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

Sponsors & Collaborators

• H3 Biomedicine Inc.: lead
• Eisai Inc.: collaborator

Study Sites (44)

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

UC Irvine Medical Center

Orange, California, 92868-3201, United States

Location

UCLA Medical Center

Santa Monica, California, 90404, United States

Location

Georgetown Unversity Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

Northwestern Unversity

Chicago, Illinois, 60611, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

John theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Duke University Cancer Center

Durham, North Carolina, 27710, United States

Location

University of Cincinnati Cancer Institute

Cincinnati, Ohio, 45219, United States

Location

University of Pennsylsvania - Perelman Cancer Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Simmons Comprehensive Cancer Center

Dallas, Texas, 75390, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

UCL Cliniques universitaires Saint-Luc

Woluwe-Saint-Lambert, Brussels Capital, 1200, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Cross Cancer Institute

Edmonton, Alberta, T6G IZ2, Canada

Location

Jurvanski Cancer Center

Hamilton, Ontario, L8V 5C2, Canada

Location

Institut Bergonié

Bordeaux, 33076, France

Location

Centre Oscar Lambret

Lille, 59000, France

Location

Hôpital Haut-Lévêque - CHU de Bordeaux

Pessac, 33604, France

Location

Centre Eugène Marquis

Rennes, 35042, France

Location

IRCCS Istituto Scientifico Romagnolo per lo studio e la cura dei tumori - U.O. di Oncologia Medica

Meldola, 47014, Italy

Location

IRCCS Ospedale San Raffaele S.r.l. - PPDS

Milan, 20132, Italy

Location

Azienda Ospedaliero Universitaria - Policlinico di Modena

Modena, 41124, Italy

Location

Altay Regional Oncology Center

Barnaul, Altay, Re, 656045, Russia

Location

Russian Oncology Research Center n a N N Blokhin

Moscow, 115478, Russia

Location

Omsk Regional Oncology Center

Omsk, 644046, Russia

Location

Railway Clinical Hospital JSC RZhD

Saint Petersburg, 195271, Russia

Location

City Clinical Oncology Dispensary

Saint Petersburg, 198255, Russia

Location

National University Cancer Insitute

Singapore, 119074, Singapore

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Clínica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitario de Badajoz

Badajoz, 06080, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 8035, Spain

Location

General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

START Madrid FJD, Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

Sarah Cannon Research Institute UK - SCRI - PPDS

London, W1G 6AD, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

H3B-6527

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_oncmedinfo@eisai.com

1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: July 13, 2016
• First Posted: July 15, 2016
• Study Start: December 28, 2016
• Primary Completion: February 23, 2022
• Study Completion: February 23, 2022
• Last Updated: November 13, 2023
• Results First Posted: November 13, 2023

Record last verified: 2021-07

Locations

KR (1); RU (5); TW (2); ES (8); GB (1); US (15); CA (2); SG (1); BE (2); FR (4); IT (3)