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

Sponsor

H3 Biomedicine Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02834780

Collaborator

Eisai Inc. (Industry)

128

Enrollment

Locations

Arm

66.8

Actual Duration (Months)

2.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Hepatocellular Carcinoma Hepatocellular Carcinoma Liver Cancer Liver Neoplasms Hepatic Cancer Hepatic Carcinoma	Drug: H3B-6527	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

128 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 31, 2016

Actual Primary Completion Date :

Feb 24, 2022

Actual Study Completion Date :

Feb 24, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: H3B-6527 (escalation and expansion) Hepatocellular Carcinoma	Drug: H3B-6527 H3B-6527 by mouth once or twice daily at specified doses.

Arm

Intervention/Treatment

Experimental: H3B-6527 (escalation and expansion)

Hepatocellular Carcinoma

Drug: H3B-6527

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

Outcome Measures

Primary Outcome Measures

Number of Participants with Dose-limiting Toxicities (DLTs) [Escalation Cycle 1 (21 days)]
Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Escalation and Expansion continuously throughout the study within 30 days after last study drug dose (up to 48 months)]

Secondary Outcome Measures

Area under the Plasma Concentration-time Curve from Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 [Escalation, Cycle 1 (21-day cycles): Days 1 and 8 predose and at multiple time points (up to 24 hours) postdose, Day 15 (0 hours); Expansion, Cycle 1 (21-day cycles): Days 8 predose and at multiple time points (up to 24 hours) postdose, Day 15 (0 hours)]
Maximum Observed Plasma Concentration (Cmax) of H3B-6527 [Escalation, Cycle 1 (21-day cycles): Days 1 and 8 predose and at multiple time points (up to 24 hours) postdose, Day 15 (0 hours); Expansion, Cycle 1 (21-day cycles): Days 8 predose and at multiple time points (up to 24 hours) postdose, Day 15 (0 hours)]
Time of Maximum Observed Plasma Concentration (tmax) of H3B-6527 [Escalation, Cycle 1 (21-day cycles): Days 1 and 8 predose and at multiple time points (up to 24 hours) postdose, Day 15 (0 hours); Expansion, Cycle 1 (21-day cycles): Days 8 predose and at multiple time points (up to 24 hours) postdose, Day 15 (0 hours)]
Objective Response Rate (ORR) [Escalation and Expansion up to approximately 48 months]
Duration of Response (DOR) [Escalation and Expansion up to approximately 48 months]
Progression-free Survival (PFS) [Escalation and Expansion up to approximately 48 months]
Overall Survival (OS) [Escalation and Expansion up to approximately 48 months]
Time to Response [Escalation and Expansion up to approximately 48 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

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.

Exclusion criteria:

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.

Contacts and Locations

Locations

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