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

Phase 1

Completed

Conditions: Liver Cancer
Liver Neoplasms
Hepatic Cancer
Hepatic Carcinoma
Advanced Hepatocellular Carcinoma
Hepatocellular Carcinoma

Interventions: Drug: H3B-6527

Registration Number: NCT02834780

Lead Sponsor: H3 Biomedicine Inc.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 128

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
H3B-6527 (escalation and expansion)	H3B-6527	Hepatocellular Carcinoma

Primary Outcome Measures

Name	Time	Method
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	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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	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).
Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters	From baseline up to approximately 36.7 months	Laboratory assessment included hematology, coagulation, clinical chemistry, and urinalysis parameters.
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 Outcome Measures

Name	Time	Method
Part 2, Dose Expansion Phase: Time to Response (TTR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1	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.
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	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.
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	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).
Part 2, Dose Expansion Phase: Progression-free Survival (PFS) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1	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).
Part 2, Dose Expansion Phase: Overall Survival (OS)	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.

Trial Locations

Locations (44): USC/Norris Comprehensive Cancer Center
🇺🇸
Los Angeles, California, United States
University of Pennsylsvania - Perelman Cancer Center for Advanced Medicine
🇺🇸
Philadelphia, Pennsylvania, United States
Taichung Veterans General Hospital
🇨🇳
Taichung, Taiwan
National Cheng Kung University Hospital
🇨🇳
Tainan, Taiwan
Institut Bergonié
🇫🇷
Bordeaux, France
UC Irvine Medical Center
🇺🇸
Orange, California, United States
UCLA Medical Center
🇺🇸
Santa Monica, California, United States
UCL Cliniques universitaires Saint-Luc
🇧🇪
Woluwe-Saint-Lambert, Brussels, Belgium
START Madrid FJD, Hospital Universitario Fundacion Jimenez Diaz
🇪🇸
Madrid, Spain
Hospital Universitario HM Sanchinarro
🇪🇸
Madrid, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸
Santander, Cantabria, Spain
Sarah Cannon Research Institute UK - SCRI - PPDS
🇬🇧
London, United Kingdom
Hospital Universitario Virgen del Rocio
🇪🇸
Sevilla, Spain
John theurer Cancer Center at Hackensack University Medical Center
🇺🇸
Hackensack, New Jersey, United States
Georgetown Unversity Lombardi Comprehensive Cancer Center
🇺🇸
Washington, District of Columbia, United States
Simmons Comprehensive Cancer Center
🇺🇸
Dallas, Texas, United States
University of Texas Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
Jurvanski Cancer Center
🇨🇦
Hamilton, Ontario, Canada
Universitair Ziekenhuis Gent
🇧🇪
Gent, Belgium
Centre Oscar Lambret
🇫🇷
Lille, France
IRCCS Istituto Scientifico Romagnolo per lo studio e la cura dei tumori - U.O. di Oncologia Medica
🇮🇹
Meldola, Italy
Azienda Ospedaliero Universitaria - Policlinico di Modena
🇮🇹
Modena, Italy
IRCCS Ospedale San Raffaele S.r.l. - PPDS
🇮🇹
Milano, Italy
Altay Regional Oncology Center
🇷🇺
Barnaul, Altay, Re, Russian Federation
Russian Oncology Research Center n a N N Blokhin
🇷🇺
Moscow, Russian Federation
Asan Medical Center
🇰🇷
Seoul, Korea, Republic of
Omsk Regional Oncology Center
🇷🇺
Omsk, Russian Federation
Railway Clinical Hospital JSC RZhD
🇷🇺
Saint Petersburg, Russian Federation
City Clinical Oncology Dispensary
🇷🇺
Saint Petersburg, Russian Federation
Hospital Universitario de Badajoz
🇪🇸
Badajoz, Spain
Clínica Universidad de Navarra
🇪🇸
Pamplona, Navarra, Spain
Hospital Universitario Vall d'Hebron
🇪🇸
Barcelona, Spain
General Universitario Gregorio Maranon
🇪🇸
Madrid, Spain
Hôpital Haut-Lévêque - CHU de Bordeaux
🇫🇷
Pessac, France
Centre Eugène Marquis
🇫🇷
Rennes, France
Northwestern Unversity
🇺🇸
Chicago, Illinois, United States
Cross Cancer Institute
🇨🇦
Edmonton, Alberta, Canada
National University Cancer Insitute
🇸🇬
Singapore, Singapore
Hoag Memorial Hospital Presbyterian
🇺🇸
Newport Beach, California, United States
McGuire VA Medical Center
🇺🇸
Richmond, Virginia, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
Duke University Cancer Center
🇺🇸
Durham, North Carolina, United States
University of Cincinnati Cancer Institute
🇺🇸
Cincinnati, Ohio, United States