HCC Child-Pugh A expansion cohort: Regorafenib 100 mg
HCC Child-Pugh B expansion cohort: Regorafenib 100 mg
NSCLC expansion cohort: Regorafenib 100 mg
Countries
United States
Protocol Section
Identification Module
NCT ID
NCT01117623
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
11651
Secondary IDs
Not provided
Brief Title
Continuous Dosing of BAY73-4506 in Patients With Advanced Malignancies
Official Title
Open Label, Phase I Study to Determine the Safety, Tolerability, Maximum Tolerated Dose, Pharmacokinetics, and Biomarker Status of BAY73-4506 in Patients With Advanced Malignancies
Acronym
Not provided
Organization
BayerINDUSTRY
Status Module
Record Verification Date
Nov 2015
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Feb 2007
Primary Completion Date
Nov 2013Actual
Completion Date
Nov 2013Actual
First Submitted Date
Feb 11, 2010
First Submission Date that Met QC Criteria
May 4, 2010
First Posted Date
May 5, 2010Estimated
Results Waived
Not provided
Results First Submitted Date
Nov 17, 2014
Results First Submitted that Met QC Criteria
Jan 15, 2015
Results First Posted Date
Jan 19, 2015Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Nov 16, 2015
Last Update Posted Date
Nov 18, 2015Estimated
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
BayerINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
Continuous dosing of BAY73-4506 in patients with advanced cancer
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral co-precipitate (CP) tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Maximum Tolerated Dose (MTD)
The MTD was defined as the highest dose level, which could be given to 6 participants such that no more than 1 participant (less than 33%) experienced a dose-limiting toxicity (DLT).
Within first 4 weeks of treatment
Maximum Observed Plasma Concentration After Single Dose Administration (Cmax)
Cmax refers to the highest measured drug concentration, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose
Area Under the Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose (AUC)
The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose
Cmax at Steady State During a Dosing Interval (Cmax,ss)
Cmax,ss refers to the highest measured drug concentration, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample, after multiple dose administration and after a steady state concentration has been reached.
Blood samples were collected at on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose.
AUC From Time 0 to 24 Hours at Steady State(AUC(0-24),ss)
AUC(0-24),ss is a measure of systemic drug exposure over 24 hours, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample, after multiple dose administration and after a steady state concentration has been reached.
Secondary Outcomes
Measure
Description
Time Frame
AUC From Time 0 to the Last Data Point > Lower Limit of Quantification (LLOQ) (AUC(0-tlast))
The AUC(0-tlast) is a measure of systemic drug exposure from time 0 up to the time point at which the last measurable drug could be detectable, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose
Other Outcomes
Measure
Description
Time Frame
Tumor Progression in Dose Escalation Cohort
Tumor progression evaluates changes in a tumor or tumors over time due to worsening of disease. Measurements and observations of the tumor status were performed before, during and after treatment. Progression for solid tumors was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.0) criteria. Tumor dimensions were measured in millimeters and the longest diameter (LD) was recorded for up to 5 lesions per organ and 10 lesions total. A sum of the LD for all target lesions was recorded. The use of a 20% increase in the sum of LD of target lesions from the smallest sum or appearance of a new lesion was assessed as progression of disease.
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
18 years
Patients with advanced, histologically or cytologically confirmed solid tumors, malignant lymphomas, or multiple myeloma refractory to any standard therapy
Radiographical, hematological or clinically evaluable tumor
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
Life expectancy of at least 12 weeks
Adequate bone marrow, liver, and renal function as assessed by the following laboratory requirements:
Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN)
Signed informed consent must be obtained prior to any study specific procedures
Exclusion Criteria:
History of cardiac disease: congestive heart failure (CHF) > New York Heart Association (NYHA) Class II; active coronary artery disease, myocardial infarction within 6 months prior to study entry; new onset angina within 3 months or unstable angina or cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 90 mmHg, despite optimal medical management
History of HIV infection or chronic hepatitis B or C
Active clinically serious infections (> Grade 2 NCI Common Terminology Criteria for Adverse Events v3.0)
Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months from definitive therapy, has no evidence of tumor growth on an imaging study within 2 weeks prior to study entry and is clinically stable with respect to the tumor at the time of study entry. Patients with brain metastases must not be undergoing acute steroid therapy or steroid taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies)
Substance abuse, medical, psychological or social conditions that may interfere with the patient178s participation in the study or evaluation of the study results
Radiotherapy to the target lesions within 3 weeks prior to Day 1, Cycle 1 (first dose of study drug). (Palliative radiotherapy will be allowed). Radiotherapy to the target lesions during study will be regarded as progressive disease
Previous or concurrent cancer which is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis and T1] or any cancer curatively treated > 3 years prior to study entry.
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Bayer Study Director
Bayer
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Los Angeles
California
90095
United States
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
109 (73 male and 36 female) participants were screened according to the inclusion and exclusion criteria to determine their appropriateness for inclusion in the study, and 86 (54 male and 32 female) participants were included at 5 centers, valid for safety population, 81 participants valid for ITT efficacy analysis and PK population.
Recruitment Details
Adult participants with advanced, histologically or cytologically confirmed solid tumors (including non-small-cell lung cancer (NSCLC) participants enrolled in the expansion portion of the study), malignant lymphomas, or multiple myeloma were enrolled in 5 centers in the USA from 01 FEB 2007 to 22 Apr 2011.
Participants in the dose-escalation cohort received a single 20 mg oral co-precipitate (CP) tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 120 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 140 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Arm 5
HCC Child-Pugh A expansion cohort: Regorafenib 100 mg
Drug
Hepatocellular carcinoma (HCC) Participants with Child Pugh A in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Arm 6
HCC Child-Pugh B expansion cohort: Regorafenib 100 mg
Drug
Hepatocellular carcinoma (HCC) Participants with Child Pugh B in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Arm 7
NSCLC expansion cohort: Regorafenib 100 mg
Drug
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Arm 8
Blood samples were collected on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose.
Area Under the Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose Divided by Dose (AUC/D)
The AUC/D is a measure of systemic drug exposure (AUC) after the first single dose, which is then divided by that dose. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose
Maximum Observed Plasma Concentration After Single Dose Administration Divided by Dose (Cmax/D)
Cmax/D refers to the highest measured drug concentration after a single dose administration, which is then divided by the administered dose. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose.
Half-life Associated With the Terminal Slope (T1/2)
T1/2 is the period of time required for the concentration or amount of drug in the body to be reduced to exactly one-half of a given concentration or amount. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose.
Cmax at Steady State During a Dosing Interval Divided by Dose (Cmax,ss/D)
Cmax,ss/D refers to the highest measured drug concentration after multiple dose administration and after a steady state concentration has been reached, which is then divided by the administered dose. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Blood samples were collected at on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose
AUC From Time 0 to 24 Hours at Steady State Divided by Dose (AUC(0-24)ss/D)
AUC(0-24)ss/D is a measure of systemic drug exposure (AUC) over 24 hours after multiple dose administration and after a steady state concentration has been reached, which is then divided by the administered dose. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Blood samples were collected on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose
Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss)
Tmax,ss refers to the time after multiple dose administration and after a steady state concentration has been reached when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Blood samples were collected on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose
Ratio of Cmax,ss/Cmax (RACmax)
RACmax is the ratio of the highest drug concentration at steady state to the highest drug concentration after single dose administration. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose
Ratio of Cmin,ss/Cmin (RACmin)
RACmin is the ratio of the lowest drug concentration at steady state to the lowest drug concentration after single dose administration. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose
Ratio of AUCt,ss/AUCt (RAAUC)
RAAUC is the ratio of the measure of systemic drug exposure over a specific dosing interval at steady state to the measure of systemic drug exposure over a specific dosing interval after single dose administration. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose
Ratio of AUCt,ss/AUC (RLIN)
RLIN is the ratio of the measure of systemic drug exposure at steady state to the measure of systemic drug exposure after single dose administration. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose
The analysis of Biomarker sCEGFR-2 plasma levels is not done.
No data obtained
From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)
Tumor Progression in Expansion Cohort
Tumor progression evaluates changes in a tumor or tumors over time due to worsening of disease. Measurements and observations of the tumor status were performed before, during and after treatment. Tumor progression evaluates changes in a tumor or tumors over time due to worsening of disease. Measurements and observations of the tumor status were performed before, during and after treatment. Progression for solid tumors was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.0) criteria. Tumor dimensions were measured in millimeters and the longest diameter (LD) was recorded for up to 5 lesions per organ and 10 lesions total. A sum of the LD for all target lesions was recorded. The use of a 20% increase in the sum of LD of target lesions from the smallest sum or appearance of a new lesion was assessed as progression of disease.
From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)
Tumor Response in Dose Escalation Cohort
Tumor Response (= Best Overall Response) of a participant was defined as the best tumor response (Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes.
From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)
Tumor Response in Expansion Cohort
Tumor Response (= Best Overall Response) of a participant was defined as the best tumor response (Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes.
From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 120 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 140 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
FG005
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
FG006
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
FG007
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
BG005
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
BG006
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
BG007
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
BG008
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0003
BG0018
BG00211
BG0036
BG00410
BG00516
BG0066
BG00726
BG00886
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00063.3± 8.1
BG00155.3± 13.1
BG00261.9± 8.8
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0000
BG0013
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Maximum Tolerated Dose (MTD)
The MTD was defined as the highest dose level, which could be given to 6 participants such that no more than 1 participant (less than 33%) experienced a dose-limiting toxicity (DLT).
Safety Population; dose escalation cohorts only
Posted
Number
mg
Within first 4 weeks of treatment
ID
Title
Description
OG000
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Units
Counts
Participants
OG00037
Title
Denominators
Categories
Title
Measurements
OG000100
Primary
Maximum Observed Plasma Concentration After Single Dose Administration (Cmax)
Cmax refers to the highest measured drug concentration, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Pharmacokinetic population; Number of Participants with an evaluable Cmax in at least one analyte was 1 (M5) in 20mg; 7 (regorafenib and M2) and 5 (M5) in 40mg; 13 (M5) in HCC Child-Pugh A; 22 (M5) in NSCLC
Posted
Geometric Mean
Geometric Coefficient of Variation
mg/L
Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Primary
Area Under the Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose (AUC)
The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
PK population; Number of Participants with at least one evaluable AUC were 5 (regorafenib) and 6 (M2) in 40mg; 5 (regorafenib and M2) in 100 mg; 3 (M2) in 120 mg; 6 (regorafenib and M2) in 140 mg; 9 (regorafenib), 10 (M2) and 1 (M5) in HCC Child Pugh A; 3 (regorafenib) and 2 (M2) in HCC Child Pugh B; 19 (regorafenib) and 16 (M2) in NSCLC
Posted
Geometric Mean
Geometric Coefficient of Variation
mg*h/L
Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Primary
Cmax at Steady State During a Dosing Interval (Cmax,ss)
Cmax,ss refers to the highest measured drug concentration, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample, after multiple dose administration and after a steady state concentration has been reached.
Pharmacokinetic population; Number of Participants with an evaluable Cmax,ss in at least one analyte were 6 in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC
Posted
Geometric Mean
Geometric Coefficient of Variation
mg/L
Blood samples were collected at on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose.
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Primary
AUC From Time 0 to 24 Hours at Steady State(AUC(0-24),ss)
AUC(0-24),ss is a measure of systemic drug exposure over 24 hours, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample, after multiple dose administration and after a steady state concentration has been reached.
Pharmacokinetic population; Number of Participants with an evaluable AUC(0-24),ss in at least one analyte in at least one analyte were 6 in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC
Posted
Geometric Mean
Geometric Coefficient of Variation
mg*h/mL
Blood samples were collected on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose.
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Secondary
AUC From Time 0 to the Last Data Point > Lower Limit of Quantification (LLOQ) (AUC(0-tlast))
The AUC(0-tlast) is a measure of systemic drug exposure from time 0 up to the time point at which the last measurable drug could be detectable, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Pharmacokinetic population; Number of Participants with an evaluable AUC(0-tlast) in at least one analyte were 1(M-5) in 20mg; 7 (regorafenib and M-2) and 5 (M-5) in 40mg; 13 (M-5) in HCC Child Pugh A; 22 (M5) in NSCLC
Posted
Geometric Mean
Geometric Coefficient of Variation
mg*h/L
Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Secondary
Area Under the Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose Divided by Dose (AUC/D)
The AUC/D is a measure of systemic drug exposure (AUC) after the first single dose, which is then divided by that dose. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
PK population; Number of Participants with at least one evaluable AUC/D were 5 (regorafenib) and 6 (M-2) in 40mg; 5 (regorafenib and M-2) in 100 mg; 3 (M-2) in 120 mg; 6 (regorafenib and M-2) in 140 mg; 9 (regorafenib), 10 (M-2) and 1 (M5) in HCC Child Pugh A; 3 (regorafenib) and 2 (M-2) in HCC Child Pugh B; 19 (regorafenib) and 16 (M-2) in NSCLC
Posted
Geometric Mean
Geometric Coefficient of Variation
h/L
Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Maximum Observed Plasma Concentration After Single Dose Administration Divided by Dose (Cmax/D)
Cmax/D refers to the highest measured drug concentration after a single dose administration, which is then divided by the administered dose. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Pharmacokinetic population; Number of Participants with an evaluable Cmax/D in at least one analyte was 1 (M5) in 20mg; 7 (regorafenib and M2) and 5 (M5) in 40mg; 13 (M5) in HCC Child-Pugh A; 22 (M5) in NSCLC
Posted
Geometric Mean
Geometric Coefficient of Variation
1/L
Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Pharmacokinetic population; Number of Participants with an evaluable Tmax in at least one analyte were 1 (M-5) in 20 mg; 5 (M-5) in 40mg; 13 (M-5) in HCC Child Pugh A; 22 (M-5) in NSCLC
Posted
Median
Full Range
h
Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose.
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Secondary
Half-life Associated With the Terminal Slope (T1/2)
T1/2 is the period of time required for the concentration or amount of drug in the body to be reduced to exactly one-half of a given concentration or amount. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
PK population; Number of Patients with at least an evaluable T1/2 were 5 (regorafenib) and 6 (M2) in 40mg; 5 (regorafenib and M2) in 100 mg; 3 (regorafenib and M2) in 120 mg; 6 (regorafenib and M2) in 140 mg; 9 (regorafenib), 10(M2) and 1 (M5) in HCC Child Pugh A; 3 (regorafenib) and 2 (M2) in HCC Child Pugh B; 19 (regorafenib) and 16 (M2) in NSCLC
Posted
Geometric Mean
Geometric Coefficient of Variation
h
Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose.
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Secondary
Cmax at Steady State During a Dosing Interval Divided by Dose (Cmax,ss/D)
Cmax,ss/D refers to the highest measured drug concentration after multiple dose administration and after a steady state concentration has been reached, which is then divided by the administered dose. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Pharmacokinetic population; Number of Participants with an evaluable Cmax,ss/D in at least one analyte were 6 in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC
Posted
Geometric Mean
Geometric Coefficient of Variation
1/L
Blood samples were collected at on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Secondary
AUC From Time 0 to 24 Hours at Steady State Divided by Dose (AUC(0-24)ss/D)
AUC(0-24)ss/D is a measure of systemic drug exposure (AUC) over 24 hours after multiple dose administration and after a steady state concentration has been reached, which is then divided by the administered dose. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Pharmacokinetic population; Number of Participants with an evaluable AUC(0-24)ss/D in at least one analyte were 6 in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC
Posted
Geometric Mean
Geometric Coefficient of Variation
h/L
Blood samples were collected on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Secondary
Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss)
Tmax,ss refers to the time after multiple dose administration and after a steady state concentration has been reached when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Pharmacokinetic population; Number of Participants with an evaluable Tmax,ss in at least one analyte were 6 in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC
Posted
Median
Full Range
h
Blood samples were collected on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Secondary
Ratio of Cmax,ss/Cmax (RACmax)
RACmax is the ratio of the highest drug concentration at steady state to the highest drug concentration after single dose administration. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Pharmacokinetic population; Number of Participants with an evaluable Cmax,ss and Cmax in at least one analyte were 1 (M5) in 20mg; 5 (regorafenib and M2) and 4 (M5) in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC
Posted
Number
Ratio
Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Secondary
Ratio of Cmin,ss/Cmin (RACmin)
RACmin is the ratio of the lowest drug concentration at steady state to the lowest drug concentration after single dose administration. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Pharmacokinetic population; Number of Participants with an evaluable Cmin,ss and Cmin in at least one analyte were 0 (M5) in 20mg; 6 (regorafenib and M2) and 4 (M5) in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC
Posted
Number
Ratio
Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Secondary
Ratio of AUCt,ss/AUCt (RAAUC)
RAAUC is the ratio of the measure of systemic drug exposure over a specific dosing interval at steady state to the measure of systemic drug exposure over a specific dosing interval after single dose administration. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Pharmacokinetic population; Number of Participants with an evaluable AUCt,ss and AUCt in at least one analyte were 0 (M5) in 20mg; 5 (regorafenib and M2) and 4 (M5) in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC
Posted
Number
Ratio
Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Secondary
Ratio of AUCt,ss/AUC (RLIN)
RLIN is the ratio of the measure of systemic drug exposure at steady state to the measure of systemic drug exposure after single dose administration. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
PK population; Number of Participants with an evaluable AUCt,ss and AUC in at least one analyte were 0 in 20mg; 3 (regorafenib) and 4 (M2) in 40mg; 3 in 100 mg; 2 (regorafenib) and 0 (M2) in 120 mg; 3 (regorafenib) and 2 (M2) in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 4 in NSCLC; No participants have evaluable data for M5.
Posted
Number
Ratio
Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
The analysis of Biomarker VEGF plasma levels is not done
ITT
Posted
No data obtained
ID
Title
Description
OG000
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
The analysis of Biomarker sCEGFR-2 plasma levels is not done.
ITT
Posted
No data obtained
ID
Title
Description
OG000
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Units
Counts
Participants
OG000
Other Pre-specified
Tumor Progression in Dose Escalation Cohort
Tumor progression evaluates changes in a tumor or tumors over time due to worsening of disease. Measurements and observations of the tumor status were performed before, during and after treatment. Progression for solid tumors was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.0) criteria. Tumor dimensions were measured in millimeters and the longest diameter (LD) was recorded for up to 5 lesions per organ and 10 lesions total. A sum of the LD for all target lesions was recorded. The use of a 20% increase in the sum of LD of target lesions from the smallest sum or appearance of a new lesion was assessed as progression of disease.
Intent-to-treat (ITT) efficacy analysis (set)
Posted
Number
Participants
From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Tumor progression evaluates changes in a tumor or tumors over time due to worsening of disease. Measurements and observations of the tumor status were performed before, during and after treatment. Tumor progression evaluates changes in a tumor or tumors over time due to worsening of disease. Measurements and observations of the tumor status were performed before, during and after treatment. Progression for solid tumors was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.0) criteria. Tumor dimensions were measured in millimeters and the longest diameter (LD) was recorded for up to 5 lesions per organ and 10 lesions total. A sum of the LD for all target lesions was recorded. The use of a 20% increase in the sum of LD of target lesions from the smallest sum or appearance of a new lesion was assessed as progression of disease.
ITT efficacy analysis (set), expansion cohorts only
Posted
Number
Participants
From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)
ID
Title
Description
OG000
HCC Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A or B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Other Pre-specified
Tumor Response in Dose Escalation Cohort
Tumor Response (= Best Overall Response) of a participant was defined as the best tumor response (Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes.
ITT efficacy analysis (set)
Posted
Number
Participants
From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Other Pre-specified
Tumor Response in Expansion Cohort
Tumor Response (= Best Overall Response) of a participant was defined as the best tumor response (Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes.
ITT efficacy analysis (set), expansion cohorts only
Posted
Number
Participants
From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)
ID
Title
Description
OG000
HCC Expansion Cohort, Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A or B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG001
NSCLC Expansion Cohort, Regorafenib 100 mg
Time Frame
Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
3
8
8
8
EG002
Regorafenib (Stivarga, BAY73-4506) 100 mg
Participants received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. This arm includes the participants from the dose escalation cohort: Regorafenib 100 mg and the three Expansion Cohorts 'HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg', 'HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg', 'NSCLC Expansion Cohort: Regorafenib 100 mg'.
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 120 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 140 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
6
10
10
10
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Edema: Limb
Blood and lymphatic system disorders
NCI-CTC v.3.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected8 at risk
EG0021 affected59 at risk
EG0030 affected6 at risk
EG0040 affected10 at risk
Cardiac General - Other
Cardiac disorders
NCI-CTC v.3.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected8 at risk
EG0023 affected59 at risk
EG003
Conduction abnormality, AV Block - 3rd Degree (Complete AV Block)
Cardiac disorders
NCI-CTC v.3.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected8 at risk
EG0021 affected59 at risk
EG003
Hypertension
Cardiac disorders
NCI-CTC v.3.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected8 at risk
EG0021 affected59 at risk
EG003
Hypotension
Cardiac disorders
NCI-CTC v.3.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected8 at risk
EG0020 affected59 at risk
EG003
Pericardial effusion
Cardiac disorders
NCI-CTC v.3.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected8 at risk
EG0021 affected59 at risk
EG003
Pericarditis
Cardiac disorders
NCI-CTC v.3.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected8 at risk
EG0021 affected59 at risk
EG003
SupraVentricular arrhythmia, Sinus tachycardia
Cardiac disorders
NCI-CTC v.3.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected8 at risk
EG0020 affected59 at risk
EG003
Blurred vision
Eye disorders
NCI-CTC v.3.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected8 at risk
EG0020 affected59 at risk
EG003
Ocular - Other
Eye disorders
NCI-CTC v.3.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected8 at risk
EG0021 affected59 at risk
EG003
Constipation
Gastrointestinal disorders
NCI-CTC v.3.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected8 at risk
EG0021 affected59 at risk
EG003
Dehydration
Gastrointestinal disorders
NCI-CTC v.3.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected8 at risk
EG0022 affected59 at risk
EG003
GI - Other
Gastrointestinal disorders
NCI-CTC v.3.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected8 at risk
EG0022 affected59 at risk
EG003
Nausea
Gastrointestinal disorders
NCI-CTC v.3.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected8 at risk
EG0022 affected59 at risk
EG003
Obstruction, GI, Duodenum
Gastrointestinal disorders
NCI-CTC v.3.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0011 affected8 at risk
EG0020 affected59 at risk
EG003
Obstruction, GI, Small bowel NOS
Gastrointestinal disorders
NCI-CTC v.3.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected8 at risk
EG0021 affected59 at risk
EG003
Constitutional Symptoms - Other
General disorders
NCI-CTC v.3.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected8 at risk
EG0021 affected59 at risk
EG003
Death not associated with CTCAE term, Disease Progression NOS
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG005
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG006
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG007
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Units
Counts
Participants
OG0003
OG0018
OG00210
OG0036
OG00410
OG00514
OG0064
OG00724
Title
Denominators
Categories
Regorafenib (n=3,7,10,6,10,14,4,24)
Title
Measurements
OG0000.330± 14.8
OG0010.422± 27.4
OG0021.25± 30.7
OG0031.87± 24.0
OG0041.90± 51.2
OG0051.38± 98
OG0061.42± 76
OG0071.25± 68.5
M2 (BAY75-7495) (n=3,7,10,6,10,14,4,24)
Title
Measurements
OG0000.0181± 244
OG0010.0867± 110
OG0020.401± 51.2
OG003
M5 (BAY81-8752) (n=1,5,10,6,10,13,4,22)
Title
Measurements
OG0000.00290± NAwe have one data point only, n=1, calculation not possible
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG005
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG006
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG007
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Units
Counts
Participants
OG0003
OG0018
OG00210
OG0036
OG00410
OG00514
OG0064
OG00724
Title
Denominators
Categories
Regorafenib (n=3,5,5,6,6,9,3,19)
Title
Measurements
OG000NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
OG00116.3± 76.3
OG00243.7± 34.9
OG00352.9± 64.6
OG00452.5± 66.4
OG00545.2± 84.3
OG00657.7± 30.9
OG00733.5± 43.9
M2 (BAY75-7495) (n=3,6,5,3,6,10,2,16)
Title
Measurements
OG000NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
OG0013.53± 161
OG00212.8± 37.0
OG003
M5 (BAY81-8752) (n=3,8,10,6,10,1,4,24)
Title
Measurements
OG000NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
OG001NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
OG002NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG005
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG006
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG007
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Units
Counts
Participants
OG0003
OG0018
OG00210
OG0036
OG00410
OG00514
OG0064
OG00724
Title
Denominators
Categories
Regorafenib (n=3,6,6,2,3,0,1,5)
Title
Measurements
OG0001.27± 19.4
OG0011.50± 37.0
OG0024.27± 22.9
OG0033.62± 5.77
OG0045.37± 30.9
OG005NA± NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG0062.69± NAwe have one data point only, n=1, calculation not possible
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG005
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG006
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG007
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Units
Counts
Participants
OG0003
OG0018
OG00210
OG0036
OG00410
OG00514
OG0064
OG00724
Title
Denominators
Categories
Regorafenib (n=3,6,6,2,3,0,1,5)
Title
Measurements
OG00012.9± 21.2
OG00118.1± 35.9
OG00249.6± 18.5
OG00340.6± 32.9
OG00460.4± 18.5
OG005NA± NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG00639.2± NAwe have one data point only, n=1, calculation not possible
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG005
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG006
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG007
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Units
Counts
Participants
OG0003
OG0018
OG00210
OG0036
OG00410
OG00514
OG0064
OG00724
Title
Denominators
Categories
Regorafenib (n=3,7,10,6,10,14,4,24)
Title
Measurements
OG0007.98± 28.0
OG0019.12± 38.8
OG00232.7± 37.9
OG00333.5± 60.4
OG00435.8± 57.0
OG00526.8± 67.5
OG00633.0± 112
OG00718.7± 55.3
M2 (BAY75-7495) (n=3,7,10,6,10,14,4,24)
Title
Measurements
OG0000.384± 330
OG0012.02± 108
OG00211.3± 47.4
OG003
M5 (BAY81-8752) (n=1,5,10,6,10,13,4,22)
Title
Measurements
OG0000.0275± NAwe have one data point only, n=1, calculation not possible
OG0010.165± 254
OG0020.976± 111
OG003
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG005
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG006
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG007
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Units
Counts
Participants
OG0003
OG0018
OG00210
OG0036
OG00410
OG00514
OG0064
OG00724
Title
Denominators
Categories
Regorafenib (n=3,5,5,6,6,9,3,19)
Title
Measurements
OG000NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
OG0010.407± 76.3
OG0020.437± 34.9
OG0030.441± 64.6
OG0040.375± 66.4
OG0050.452± 84.3
OG0060.577± 30.9
OG0070.355± 43.9
M2 (BAY75-7495) (n=3,6,5,3,6,10,2,16)
Title
Measurements
OG000NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
OG0010.0855± 161
OG0020.124± 37.0
OG003
M5 (BAY81-8752) (n=3,8,10,6,10,1,4,24)
Title
Measurements
OG000NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
OG001NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
OG002NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG005
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG006
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG007
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Units
Counts
Participants
OG0003
OG0018
OG00210
OG0036
OG00410
OG00514
OG0064
OG00724
Title
Denominators
Categories
Regorafenib (n=3,7,10,6,10,14,4,24)
Title
Measurements
OG0000.0165± 14.8
OG0010.0106± 27.4
OG0020.0125± 30.7
OG0030.0156± 24.0
OG0040.0136± 51.2
OG0050.0138± 97.9
OG0060.0142± 76.1
OG0070.0125± 68.5
M2 (BAY75-7495) (n=3,7,10,6,10,14,4,24)
Title
Measurements
OG0000.000874± 244
OG0010.00210± 110
OG0020.00388± 51.2
OG003
M5 (BAY81-8752) (n=1,5,10,6,10,13,4,22)
Title
Measurements
OG0000.000114± NAwe have one data point only, n=1, calculation not possible
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG005
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG006
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG007
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG005
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG006
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG007
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Units
Counts
Participants
OG0003
OG0018
OG00210
OG0036
OG00410
OG00514
OG0064
OG00724
Title
Denominators
Categories
Regorafenib (n=3,5,5,3,6,9,22,19)
Title
Measurements
OG000NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
OG00141.6± 41.1
OG00231.6± 32.5
OG00327.7± 47.8
OG00423.2± 43.6
OG00525.2± 52.0
OG006745.3± 79.7
OG00733.3± 64.8
M2 (BAY75-7495) (n=3,6,5,3,6,10,2,16)
Title
Measurements
OG000NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
OG00140.3± 52.3
OG00224.8± 28.6
OG003
M5 (BAY81-8752) (n=3,8,10,6,10,1,4,24)
Title
Measurements
OG000NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
OG001NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
OG002NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG005
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG006
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG007
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Units
Counts
Participants
OG0003
OG0018
OG00210
OG0036
OG00410
OG00514
OG0064
OG00724
Title
Denominators
Categories
Regorafenib (n=3,6,6,2,3,0,1,5)
Title
Measurements
OG0000.0636± 19.4
OG0010.0374± 37.0
OG0020.0427± 22.9
OG0030.0302± 5.77
OG0040.0383± 30.9
OG005NA± NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG0060.0269± NAwe have one data point only, n=1, calculation not possible
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG005
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG006
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG007
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Units
Counts
Participants
OG0003
OG0018
OG00210
OG0036
OG00410
OG00514
OG0064
OG00724
Title
Denominators
Categories
Regorafenib (n=3,6,6,2,3,0,1,5)
Title
Measurements
OG0000.644± 21.2
OG0010.452± 35.9
OG0020.496± 18.5
OG0030.338± 32.9
OG0040.431± 18.5
OG005NA± NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG0060.392± NAwe have one data point only, n=1, calculation not possible
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG005
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG006
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG007
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Units
Counts
Participants
OG0003
OG0018
OG00210
OG0036
OG00410
OG00514
OG0064
OG00724
Title
Denominators
Categories
Regorafenib (n=3,6,6,2,3,0,1,5)
Title
Measurements
OG0002.00(2.00 to 4.00)
OG0012.00(1.00 to 10.0)
OG0021.25(0.00 to 4.00)
OG0032.00(2.00 to 2.00)
OG0042.00(1.00 to 4.00)
OG005NA(NA to NA)14 participants were analyzed. Not calculated due to no participant with an evaluable data
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG005
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG006
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG007
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Units
Counts
Participants
OG0003
OG0018
OG00210
OG0036
OG00410
OG00514
OG0064
OG00724
Title
Denominators
Categories
Regorafenib (n=3,5,6,2,3,0,1,5)
Title
Measurements
OG0003.78
OG0013.34
OG0023.50
OG0031.53
OG0042.84
OG005NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG005
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG006
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG007
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Units
Counts
Participants
OG0003
OG0018
OG00210
OG0036
OG00410
OG00514
OG0064
OG00724
Title
Denominators
Categories
Regorafenib (n=3,6,6,2,3,0,1,5)
Title
Measurements
OG0004.82
OG00134.9
OG00226.1
OG003413
OG00410.9
OG005NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG0067.80
OG00714.1
M2 (BAY75-7495) (n=3,6,6,2,3,0,1,5)
Title
Measurements
OG0004.81
OG00110.4
OG00224.2
OG003
M5 (BAY81-8752) (n=0,4,,6,2,3,0,1,5)
Title
Measurements
OG000NA3 participants were analyzed. Not calculated due to no participant with an evaluable data
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG005
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG006
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG007
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Units
Counts
Participants
OG0003
OG0018
OG00210
OG0036
OG00410
OG00514
OG0064
OG00724
Title
Denominators
Categories
Regorafenib (n=3,5,6,2,3,0,1,5)
Title
Measurements
OG0003.20
OG0013.78
OG0023.15
OG0031.37
OG0043.61
OG005NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG0062.10
OG0072.67
M2 (BAY75-7495) (n=3,5,6,2,3,0,1,5)
Title
Measurements
OG0005.79
OG0014.72
OG0024.63
OG003
M5 (BAY81-8752) (n=0,4,,6,2,3,0,1,5)
Title
Measurements
OG000NA3 participants were analyzed. Not calculated due to no participant with an evaluable data
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG005
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG006
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
OG007
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Units
Counts
Participants
OG0003
OG0018
OG00210
OG0036
OG00410
OG00514
OG0064
OG00724
Title
Denominators
Categories
Regorafenib (n=0,3,3,2,3,0,1,4)
Title
Measurements
OG000NA3 participants were analyzed. Not calculated due to no participant with an evaluable data
OG0011.53
OG0021.27
OG0030.600
OG0042.20
OG005NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG0060.800
OG0071.11
M2 (BAY75-7495) (n=0,4,3,0,2,0,1,4)
Title
Measurements
OG000NA3 participants were analyzed. Not calculated due to no participant with an evaluable data
OG0011.63
OG0022.13
OG003
M5 (BAY81-8752) (n=0)
Title
Measurements
OG000NA3 participants were analyzed. Not calculated due to no participant with an evaluable data
OG001NA8 participants were analyzed. Not calculated due to no participant with an evaluable data
OG002NA10 participants were analyzed. Not calculated due to no participant with an evaluable data
OG003
0
0
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Units
Counts
Participants
OG0003
OG0018
OG00211
OG0035
OG00410
Title
Denominators
Categories
Participants without progression
Title
Measurements
OG0001
OG0013
OG0029
OG0032
OG0045
Participants with progression
Title
Measurements
OG0002
OG0015
OG0022
OG003
OG001
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Units
Counts
Participants
OG0003
OG0018
OG00211
OG0035
OG00410
Title
Denominators
Categories
Not assessable
Title
Measurements
OG0000
OG0011
OG0022
OG0030
OG0040
Partial Response (PR)
Title
Measurements
OG0000
OG0010
OG0022
OG003
Stable Disease (SD)
Title
Measurements
OG0001
OG0012
OG0025
OG003
Progressive Disease (PD)
Title
Measurements
OG0002
OG0014
OG0022
OG003
Progression
Title
Measurements
OG0000
OG0011
OG0020
OG003
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Units
Counts
Participants
OG00022
OG00122
Title
Denominators
Categories
Not assessable
Title
Measurements
OG0003
OG0011
Partial Response (PR)
Title
Measurements
OG0001
OG0010
Stable Disease (SD)
Title
Measurements
OG0006
OG0015
Progressive Disease (PD)
Title
Measurements
OG00010
OG00112
Progression
Title
Measurements
OG0002
OG0014
0 affected
6 at risk
EG0042 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
2 affected
6 at risk
EG0043 affected10 at risk
1 affected
6 at risk
EG0041 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
1 affected
6 at risk
EG0041 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0041 affected10 at risk
2 affected
6 at risk
EG0042 affected10 at risk
2 affected
6 at risk
EG0041 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0043 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0041 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
2 affected
6 at risk
EG0042 affected10 at risk
3 affected
6 at risk
EG0043 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
2 affected
6 at risk
EG0044 affected10 at risk
1 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0042 affected10 at risk
2 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0041 affected10 at risk
3 affected
6 at risk
EG0044 affected10 at risk
2 affected
6 at risk
EG0043 affected10 at risk
2 affected
6 at risk
EG0041 affected10 at risk
1 affected
6 at risk
EG0042 affected10 at risk
1 affected
6 at risk
EG0041 affected10 at risk
4 affected
6 at risk
EG0045 affected10 at risk
1 affected
6 at risk
EG0042 affected10 at risk
0 affected
6 at risk
EG0044 affected10 at risk
2 affected
6 at risk
EG0043 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
4 affected
6 at risk
EG0042 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0042 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
5 affected
6 at risk
EG0045 affected10 at risk
2 affected
6 at risk
EG0041 affected10 at risk
2 affected
6 at risk
EG0041 affected10 at risk
4 affected
6 at risk
EG0043 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
1 affected
6 at risk
EG0043 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0042 affected10 at risk
1 affected
6 at risk
EG0042 affected10 at risk
1 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0042 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
1 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
1 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0042 affected10 at risk
0 affected
6 at risk
EG0045 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0043 affected10 at risk
1 affected
6 at risk
EG0042 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
2 affected
6 at risk
EG0042 affected10 at risk
1 affected
6 at risk
EG0041 affected10 at risk
1 affected
6 at risk
EG0042 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
1 affected
6 at risk
EG0041 affected10 at risk
2 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
2 affected
6 at risk
EG0041 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0041 affected10 at risk
2 affected
6 at risk
EG0043 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
1 affected
6 at risk
EG0041 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
1 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
2 affected
6 at risk
EG0042 affected10 at risk
1 affected
6 at risk
EG0040 affected10 at risk
2 affected
6 at risk
EG0042 affected10 at risk
0 affected
6 at risk
EG0042 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0042 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
1 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
2 affected
6 at risk
EG0044 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
1 affected
6 at risk
EG0042 affected10 at risk
5 affected
6 at risk
EG0049 affected10 at risk
0 affected
6 at risk
EG0040 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0 affected
6 at risk
EG0041 affected10 at risk
0.645
± 43.2
OG0040.606± 97.2
OG0050.42± 154
OG0060.54± 129
OG0070.388± 190
0.0459
± 59.2
OG0040.0500± 140
OG0050.036± 110
OG0060.035± 352
OG0070.321± 142
21.0
± 71.5
OG00419.5± 20.3
OG00515.3± 69.9
OG00627.2± 74.6
OG00711.6± 77.8
NA
± NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
OG004NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
OG00515.8± NAwe have one data point only, n=1, calculation not possible
OG006NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
OG007NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
2.97
± 217
OG0042.20± 106
OG005NA± NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG0062.40± NAwe have one data point only, n=1, calculation not possible
OG0070.911± 126
3.29
± 1400
OG0040.948± 343
OG005NA± NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG0061.59± NAwe have one data point only, n=1, calculation not possible
OG0070.349± 153
40.9
± 245
OG00429.7± 88.8
OG005NA± NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG00646.8± NAwe have one data point only, n=1, calculation not possible
OG00714.6± 104
44.4
± 3050
OG00412.9± 231
OG005NA± NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG00634.3± NAwe have one data point only, n=1, calculation not possible
OG0076.17± 133
14.2
± 53.4
OG00413.6± 82.6
OG0058.84± 122
OG00613.4± 194
OG0076.54± 156
1.51
± 71.1
OG0041.54± 71.1
OG0051.02± 122
OG0060.821± 587
OG0070.821± 254
0.169
± 71.5
OG0040.135± 20.3
OG0050.148± 69.9
OG0060.263± 74.6
OG0070.113± 77.8
NA
± NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
OG004NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
OG0050.0157± NAwe have one data point only, n=1, calculation not possible
OG006NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
OG007NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
0.00520
± 43.2
OG0040.00419± 97.2
OG0050.00404± 154
OG0060.00526± 129
OG0070.00376± 190
0.000381
± 59.2
OG0040.000355± 140
OG0050.000355± 110
OG0060.000351± 352
OG0070.000320± 142
9.00
(2.00 to 24.0)
OG0044.00(2.00 to 24.7)
OG0053.01(2.00 to 24.0)
OG00610.0(8.00 to 24.1)
OG0072.01(2.00 to 48.0)
24.6
(10.0 to 48.0)
OG00447.6(24.1 to 48.0)
OG00546.8(4.00 to 48.6)
OG00634.9(24.0 to 46.8)
OG00747.8(4.00 to 48.4)
22.9
± 27.6
OG00422.7± 64.7
OG00524.0± 56.3
OG00619.2± 16.4
OG00726.4± 73.4
NA
± NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
OG004NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
OG00568.7± NAwe have one data point only, n=1, calculation not possible
OG006NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
OG007NA± NAnot calculated due to no evaluable data (i.e. insufficient plasma concentrations)
0.0240
± 217
OG0040.0152± 106
OG005NA± NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG0060.0232± NAwe have one data point only, n=1, calculation not possible
OG0070.00881± 126
0.0273
± 1400
OG0040.00674± 343
OG005NA± NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG0060.0159± NAwe have one data point only, n=1, calculation not possible
OG0070.00347± 153
0.330
± 245
OG0040.205± 88.8
OG005NA± NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG0060.453± NAwe have one data point only, n=1, calculation not possible
OG0070.141± 104
0.368
± 3050
OG0040.0916± 231
OG005NA± NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG0060.342± NAwe have one data point only, n=1, calculation not possible
OG0070.0615± 133
2.00
(2.00 to 2.00)
OG0042.00(1.00 to 8.00)
OG005NA(NA to NA)14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG00610.0(10.0 to 10.0)
OG0074.00(2.00 to 10.0)
1.50
(1.00 to 2.00)
OG0041.00(0.00 to 8.00)
OG005NA(NA to NA)14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG0060.00(0.00 to 0.00)
OG0074.00(0.00 to 10.0)
3.06
OG0043.33
OG005NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG0063.40
OG0071.83
39.3
OG00418.9
OG005NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG00645.0
OG00711.9
12.6
OG0043.33
OG005NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG006103
OG00711.5
335
OG00446.2
OG005NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG006257
OG00722.4
2.71
OG0043.60
OG005NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG0064.60
OG0072.74
34.7
OG00423.9
OG005NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG00663.0
OG00718.5
NA
6 participants were analyzed. Not calculated due to no participant with an evaluable data
OG0041.39
OG005NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG0062.70
OG0071.27
NA
6 participants were analyzed. Not calculated due to no participant with an evaluable data
OG004NA10 participants were analyzed. Not calculated due to no participant with an evaluable data
OG005NA14 participants were analyzed. Not calculated due to no participant with an evaluable data
OG006NA4 participants were analyzed. Not calculated due to no participant with an evaluable data
OG007NA24 participants were analyzed. Not calculated due to no participant with an evaluable data