Advanced Hepatocellular Carcinoma, Hepatic Cancer, Hepatic Carcinoma, Hepatocellular Carcinoma, Liver Cancer, Liver Neoplasms
Conditions
Keywords
Advanced Hepatocellular Carcinoma, H3B-6527, Fibroblast growth factor receptor 4 (FGFR4), Fibroblast growth factor 19 (FGF19)
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.
Interventions
DRUGH3B-6527
H3B-6527 by mouth once or twice daily at specified doses.
Sponsors
Eisai Inc.
H3 Biomedicine Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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) | — |
| 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. |
| 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. |
| 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). |
Countries
Belgium, Canada, France, Italy, Russia, Singapore, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study at 54 investigative sites in Belgium, Canada, France, Italy, Republic of Korea, Russian Federation, Singapore, Spain, Taiwan and the United States from 28 December 2016 to 23 February 2022.
Pre-assignment details
A total of 304 participants were screened, of which 176 were screen failures and 128 were enrolled into two parts: Dose Escalation Phase (Part 1) and Dose Expansion Phase (Part 2) to receive study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted Participants received H3B-6527 300 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor. | 3 |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor. | 3 |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor. | 4 |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor. | 10 |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor. | 3 |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor. | 7 |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor. | 4 |
| Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed Participants received H3B-6527 2000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor. | 7 |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor. | 3 |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor. | 10 |
| Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed Participants received H3B-6527 700 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor. | 5 |
| Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle either in fasted or fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor. | 29 |
| Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor. | 40 |
| Total | 128 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 2 | 0 | 3 | 2 |
| Overall Study | Disease Progression - Clinically Confirmed | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 2 | 0 | 2 | 1 | 2 | 5 |
| Overall Study | Disease Progression -Radiologically Confirmed | 1 | 3 | 2 | 7 | 1 | 6 | 2 | 4 | 3 | 6 | 3 | 24 | 32 |
| Overall Study | Other | 1 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted | Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted | Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed | Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted | Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed | Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted | Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed | Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed | Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted | Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed | Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed | Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD | Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 59.0 years STANDARD_DEVIATION 7 | 72.7 years STANDARD_DEVIATION 4.73 | 68.5 years STANDARD_DEVIATION 9.75 | 67.1 years STANDARD_DEVIATION 8.01 | 68.7 years STANDARD_DEVIATION 6.51 | 59.3 years STANDARD_DEVIATION 12.22 | 60.3 years STANDARD_DEVIATION 7.14 | 62.1 years STANDARD_DEVIATION 7.52 | 68.7 years STANDARD_DEVIATION 4.04 | 62.0 years STANDARD_DEVIATION 16.51 | 65.6 years STANDARD_DEVIATION 9.91 | 61.4 years STANDARD_DEVIATION 10.67 | 64.3 years STANDARD_DEVIATION 10.58 | 63.6 years STANDARD_DEVIATION 10.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 4 Participants | 9 Participants | 3 Participants | 7 Participants | 4 Participants | 6 Participants | 3 Participants | 9 Participants | 5 Participants | 27 Participants | 28 Participants | 111 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 10 Participants | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 5 Participants | 2 Participants | 8 Participants | 7 Participants | 30 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 10 Participants | 11 Participants |
| Race (NIH/OMB) White | 2 Participants | 3 Participants | 2 Participants | 9 Participants | 1 Participants | 4 Participants | 1 Participants | 7 Participants | 3 Participants | 4 Participants | 3 Participants | 20 Participants | 22 Participants | 81 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 3 Participants | 2 Participants | 3 Participants | 1 Participants | 3 Participants | 2 Participants | 7 Participants | 12 Participants | 37 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 2 Participants | 8 Participants | 3 Participants | 4 Participants | 2 Participants | 4 Participants | 2 Participants | 7 Participants | 3 Participants | 22 Participants | 28 Participants | 91 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 3 / 3 | 2 / 4 | 6 / 10 | 2 / 3 | 7 / 7 | 3 / 4 | 1 / 7 | 3 / 3 | 6 / 10 | 4 / 5 | 19 / 29 | 31 / 40 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 4 / 4 | 10 / 10 | 3 / 3 | 7 / 7 | 4 / 4 | 7 / 7 | 3 / 3 | 9 / 10 | 5 / 5 | 28 / 29 | 39 / 40 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 1 / 4 | 1 / 10 | 1 / 3 | 4 / 7 | 1 / 4 | 2 / 7 | 2 / 3 | 3 / 10 | 1 / 5 | 11 / 29 | 17 / 40 |
Outcome results
Primary
Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters
Time frame: From baseline up to approximately 36.7 months
Population: Safety analysis set included all participants who received at least 1 dose of the study drug. This outcome measure was planned to be analyzed for Part 1 and Part 2.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters | 0 Participants |
| Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters | 0 Participants |
Primary
Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters
Laboratory assessment included hematology, coagulation, clinical chemistry, and urinalysis parameters.
Time frame: From baseline up to approximately 36.7 months
Population: Safety analysis set included all participants who received at least 1 dose of the study drug. This outcome measure was planned to be analyzed for Part 1 and Part 2.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Urinalysis | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Clinical Chemistry | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Coagulation | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Hematology | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Clinical Chemistry | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Urinalysis | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Coagulation | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Hematology | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Urinalysis | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Coagulation | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Clinical Chemistry | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Hematology | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Urinalysis | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Coagulation | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Clinical Chemistry | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Hematology | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Hematology | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Coagulation | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Clinical Chemistry | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Urinalysis | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Urinalysis | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Hematology | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Clinical Chemistry | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Coagulation | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Coagulation | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Hematology | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Clinical Chemistry | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Urinalysis | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Clinical Chemistry | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Urinalysis | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Coagulation | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Hematology | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Coagulation | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Hematology | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Urinalysis | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Clinical Chemistry | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Clinical Chemistry | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Urinalysis | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Coagulation | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Hematology | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Urinalysis | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Hematology | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Coagulation | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Clinical Chemistry | 0 Participants |
| Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Urinalysis | 0 Participants |
| Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Hematology | 0 Participants |
| Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Clinical Chemistry | 0 Participants |
| Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Coagulation | 0 Participants |
| Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Clinical Chemistry | 0 Participants |
| Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Coagulation | 0 Participants |
| Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Urinalysis | 0 Participants |
| Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed | Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters | Hematology | 0 Participants |
Primary
Number of Participants With Clinically Significant Change From Baseline in Vital Sign Parameters
Time frame: From baseline up to approximately 36.7 months
Population: Safety analysis set included all participants who received at least 1 dose of the study drug. This outcome measure was planned to be analyzed for Part 1 and Part 2.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Sign Parameters | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Sign Parameters | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Vital Sign Parameters | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Sign Parameters | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Vital Sign Parameters | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Sign Parameters | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Vital Sign Parameters | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed | Number of Participants With Clinically Significant Change From Baseline in Vital Sign Parameters | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Sign Parameters | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed | Number of Participants With Clinically Significant Change From Baseline in Vital Sign Parameters | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed | Number of Participants With Clinically Significant Change From Baseline in Vital Sign Parameters | 0 Participants |
| Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD | Number of Participants With Clinically Significant Change From Baseline in Vital Sign Parameters | 0 Participants |
| Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed | Number of Participants With Clinically Significant Change From Baseline in Vital Sign Parameters | 0 Participants |
Primary
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).
Time frame: From the first dose of study drug up to approximately 36.7 months
Population: Safety analysis set included all participants who received at least 1 dose of the study drug. This outcome measure was planned to be analyzed for Part 1 and Part 2.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 3 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 3 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 4 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 1 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 10 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 1 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 1 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 3 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 4 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 7 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 4 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 1 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 7 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 2 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 3 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 2 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 3 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 9 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 1 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 5 Participants |
| Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 28 Participants |
| Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 11 Participants |
| Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 17 Participants |
| Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 40 Participants |
Primary
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.
Time frame: Cycle 1 (Cycle length = 21 days)
Population: DLT analysis set included all participants in Dose Escalation phase (Part 1) who must have completed safety assessments through pre-dose on Cycle 2 Day 1 and must have received at least 17 of 21 (approximately 80 percent \[%\]) study days within Cycle 1, unless due to a DLT. This outcome measure was planned to be analyzed for Part 1 only.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted | 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 | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted | 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 | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed | 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 | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted | 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 | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed | 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 | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted | 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 | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed | 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 | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed | 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 | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted | 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 | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed | 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 | 0 Participants |
| Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed | 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 | 0 Participants |
Secondary
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)
Population: Pharmacokinetic (PK) analysis set: Participants who received at least 1 dose of study drug and had at least 1 evaluable plasma concentration. 'Overall Number of participants analyzed' signifies those who were evaluable for this outcome measure; 'Number analyzed' signifies participants who were evaluable at given timepoints. As planned, PK data was collected and reported together due to same dose and food conditions in Part 1 and 2 for H3B-6527 1000 mg (QD fed and fasted) and 500 mg (BID fed).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted | Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 | Cycle 1 Day 1 | 68.9 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 57.5 |
| Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted | Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 | Cycle 1 Day 8 | 50.8 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 47.5 |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted | Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 | Cycle 1 Day 1 | 173 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 1891.9 |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted | Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 | Cycle 1 Day 8 | 636 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 39.4 |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed | Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 | Cycle 1 Day 1 | 1631 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 271.8 |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed | Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 | Cycle 1 Day 8 | 484 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 3217.3 |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted | Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 | Cycle 1 Day 1 | 850 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 531.5 |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted | Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 | Cycle 1 Day 8 | 784 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 431.8 |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed | Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 | Cycle 1 Day 1 | 1115 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 909.7 |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed | Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 | Cycle 1 Day 8 | 798 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 337.8 |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted | Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 | Cycle 1 Day 8 | 1244 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 827.7 |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted | Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 | Cycle 1 Day 1 | 400 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 187.5 |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed | Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 | Cycle 1 Day 8 | 5447 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 74.9 |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed | Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 | Cycle 1 Day 1 | 5671 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 98.7 |
| Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed | Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 | Cycle 1 Day 1 | 2748 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 66.3 |
| Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed | Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 | Cycle 1 Day 8 | 1838 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 179.3 |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted | Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 | Cycle 1 Day 1 | 462 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 137 |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted | Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 | Cycle 1 Day 8 | 1056 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 36.9 |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed | Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 | Cycle 1 Day 1 | 752 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 204.3 |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed | Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 | Cycle 1 Day 8 | 809 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 237.3 |
| Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed | Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 | Cycle 1 Day 1 | 576 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 482.6 |
| Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed | Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 | Cycle 1 Day 8 | 622 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 351.1 |
Secondary
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)
Population: PK analysis set: Participants who received at least 1 dose of study drug and had at least 1 evaluable plasma concentration. 'Overall Number of participants analyzed' signifies those who were evaluable for this outcome measure; 'Number analyzed' signifies participants who were evaluable at given timepoints. As planned, PK data was collected and reported together due to same dose and food conditions in Part 1 and 2 for H3B-6527 1000 mg (QD fed and fasted) and 500 mg (BID fed).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted | Maximum Observed Plasma Concentration (Cmax) of H3B-6527 | Cycle 1 Day 1 | 20.3 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 64.1 |
| Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted | Maximum Observed Plasma Concentration (Cmax) of H3B-6527 | Cycle 1 Day 8 | 10.8 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 90.6 |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted | Maximum Observed Plasma Concentration (Cmax) of H3B-6527 | Cycle 1 Day 1 | 74.5 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 1389.4 |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted | Maximum Observed Plasma Concentration (Cmax) of H3B-6527 | Cycle 1 Day 8 | 194 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 45.6 |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed | Maximum Observed Plasma Concentration (Cmax) of H3B-6527 | Cycle 1 Day 1 | 395 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 133.7 |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed | Maximum Observed Plasma Concentration (Cmax) of H3B-6527 | Cycle 1 Day 8 | 99.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 5300.4 |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted | Maximum Observed Plasma Concentration (Cmax) of H3B-6527 | Cycle 1 Day 1 | 225 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 470.2 |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted | Maximum Observed Plasma Concentration (Cmax) of H3B-6527 | Cycle 1 Day 8 | 187 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 339.1 |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed | Maximum Observed Plasma Concentration (Cmax) of H3B-6527 | Cycle 1 Day 1 | 182 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 494.6 |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed | Maximum Observed Plasma Concentration (Cmax) of H3B-6527 | Cycle 1 Day 8 | 177 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 370.3 |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted | Maximum Observed Plasma Concentration (Cmax) of H3B-6527 | Cycle 1 Day 8 | 362 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 898.5 |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted | Maximum Observed Plasma Concentration (Cmax) of H3B-6527 | Cycle 1 Day 1 | 136 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 429.4 |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed | Maximum Observed Plasma Concentration (Cmax) of H3B-6527 | Cycle 1 Day 8 | 827 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 40.6 |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed | Maximum Observed Plasma Concentration (Cmax) of H3B-6527 | Cycle 1 Day 1 | 904 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 34.2 |
| Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed | Maximum Observed Plasma Concentration (Cmax) of H3B-6527 | Cycle 1 Day 1 | 540 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 79.9 |
| Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed | Maximum Observed Plasma Concentration (Cmax) of H3B-6527 | Cycle 1 Day 8 | 502 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 95.2 |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted | Maximum Observed Plasma Concentration (Cmax) of H3B-6527 | Cycle 1 Day 1 | 124 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 159.1 |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted | Maximum Observed Plasma Concentration (Cmax) of H3B-6527 | Cycle 1 Day 8 | 251 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 46.5 |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed | Maximum Observed Plasma Concentration (Cmax) of H3B-6527 | Cycle 1 Day 1 | 255 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 251.6 |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed | Maximum Observed Plasma Concentration (Cmax) of H3B-6527 | Cycle 1 Day 8 | 211 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 237.2 |
| Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed | Maximum Observed Plasma Concentration (Cmax) of H3B-6527 | Cycle 1 Day 1 | 163 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 303.2 |
| Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed | Maximum Observed Plasma Concentration (Cmax) of H3B-6527 | Cycle 1 Day 8 | 167 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 202.7 |
Secondary
Part 2, Dose Expansion Phase: Duration of Response (DOR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1
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).
Time frame: From the date of first documented CR or PR up to approximately 36.7 months
Population: Full analysis set included all participants who received at least 1 dose of the study drug. Here, overall number of participants analyzed N included the participants who had CR or PR. This outcome measure was planned to be analyzed for Part 2 only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted | Part 2, Dose Expansion Phase: Duration of Response (DOR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1 | NA months |
Secondary
Part 2, Dose Expansion Phase: Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1
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.
Time frame: From the first dose date until disease progression/recurrence or up to approximately 36.7 months
Population: Full analysis set included all participants who received at least 1 dose of the study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure. This outcome measure was planned to be analyzed for Part 2 only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted | Part 2, Dose Expansion Phase: Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1 | 5.6 percentage of participants |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted | Part 2, Dose Expansion Phase: Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1 | 0.0 percentage of participants |
Secondary
Part 2, Dose Expansion Phase: Overall Survival (OS)
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.
Time frame: From the date of first dose of study drug until date of death from any cause (up to approximately 36.7 months)
Population: Full analysis set included all participants who received at least 1 dose of the study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure. This outcome measure was planned to be analyzed for Part 2 only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted | Part 2, Dose Expansion Phase: Overall Survival (OS) | 9.5 months |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted | Part 2, Dose Expansion Phase: Overall Survival (OS) | 7.7 months |
Secondary
Part 2, Dose Expansion Phase: Progression-free Survival (PFS) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1
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).
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
Population: Full analysis set included all participants who received at least 1 dose of the study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure. This outcome measure was planned to be analyzed for Part 2 only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted | Part 2, Dose Expansion Phase: Progression-free Survival (PFS) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1 | 2.6 months |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted | Part 2, Dose Expansion Phase: Progression-free Survival (PFS) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1 | 3.0 months |
Secondary
Part 2, Dose Expansion Phase: Time to Response (TTR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1
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.
Time frame: From date of first dose of study drug until CR or PR (up to approximately 36.7 months)
Population: Full analysis set included all participants who received at least 1 dose of the study drug. Here, overall number of participants analyzed signifies participants who had CR or PR. This outcome measure was planned to be analyzed for Part 2 only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted | Part 2, Dose Expansion Phase: Time to Response (TTR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1 | NA months |
Secondary
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)
Population: PK analysis set: Participants who received at least 1 dose of study drug and had at least 1 evaluable plasma concentration. 'Overall Number of participants analyzed' signifies those who were evaluable for this outcome measure; 'Number analyzed' signifies participants who were evaluable at given timepoints. As planned, PK data was collected and reported together due to same dose and food conditions in Part 1 and 2 for H3B-6527 1000 mg (QD fed and fasted) and 500 mg (BID fed).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted | Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 | Cycle 1 Day 1 | 2.00 hours |
| Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted | Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 | Cycle 1 Day 8 | 4.00 hours |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted | Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 | Cycle 1 Day 1 | 1.00 hours |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted | Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 | Cycle 1 Day 8 | 0.52 hours |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed | Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 | Cycle 1 Day 1 | 4.00 hours |
| Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed | Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 | Cycle 1 Day 8 | 4.52 hours |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted | Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 | Cycle 1 Day 1 | 2.02 hours |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted | Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 | Cycle 1 Day 8 | 2.00 hours |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed | Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 | Cycle 1 Day 1 | 6.00 hours |
| Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed | Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 | Cycle 1 Day 8 | 2.00 hours |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted | Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 | Cycle 1 Day 8 | 2.10 hours |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted | Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 | Cycle 1 Day 1 | 1.00 hours |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed | Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 | Cycle 1 Day 8 | 5.86 hours |
| Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed | Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 | Cycle 1 Day 1 | 5.00 hours |
| Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed | Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 | Cycle 1 Day 1 | 2.100 hours |
| Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed | Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 | Cycle 1 Day 8 | 4.00 hours |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted | Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 | Cycle 1 Day 1 | 2.12 hours |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted | Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 | Cycle 1 Day 8 | 4.00 hours |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed | Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 | Cycle 1 Day 1 | 4.02 hours |
| Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed | Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 | Cycle 1 Day 8 | 4.00 hours |
| Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed | Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 | Cycle 1 Day 1 | 2.02 hours |
| Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed | Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 | Cycle 1 Day 8 | 4.12 hours |