Neoplasms
Conditions
Keywords
Phase I, Dose escalation, refractory, locally advanced or metastatic solid tumor, Bladder cancer, squamous non-small cell lung cancer, pan-FGFR inhibitor, lung adenocarcinoma, head and neck cancer
Brief summary
* This was the first study where BAY1163877 was given to humans. Impact of the study was to evaluate if patients with advanced solid cancers show advanced clinical benefit under the treatment with the pan FGFR inhibitor. Patients (all comers) received the study drug treatment in a dose-escalation scheme (no placebo group) to determine the safety, tolerability and maximum tolerated dose (MTD) of BAY1163877. The relative bioavailability of liquid service formulation and tablets was determined. * After the MTD was defined patients with solid tumors (all comers), lung cancer (lung adenocarcinoma & squamous non-small cell lung cancer), head and neck cancer or bladder cancer was enrolled according to their FGFR expression profile (biomarker stratification). * The study also assessed the pharmacokinetics, biomarker status, pharmacodynamic parameters and tumor response of BAY1163877. * BAY1163877 was given twice daily as oral application. Treatment was stopped if the tumor continued to grow, if side effects, which the patient cannot tolerate, occurred or if the patient decided to exit treatment.
Interventions
DRUGRogaratinib (BAY1163877) oral solution
Participants received Rogaratinib oral solution as a single dose on Cycle 1 Day 1 (C1D1) and twice daily (BID) from Cycle 1 Day 3 (C1D3) onward for the remaining 19 days of Cycle 1. For subsequent cycles, study drug was administered twice daily for 21 days each Cycle.
DRUGRogaratinib (BAY1163877) oral tablet
Participants received Rogaratinib oral tablet as a single dose on C1D1 and BID from C1D3 onward for the remaining 19 days of Cycle 1. For subsequent cycles, study drug was administered twice daily for 21 days each Cycle.
DRUGRogaratinib (BAY1163877) 800 mg BID
Participants received Rogaratinib 800 mg oral tablet as a single dose on C1D1 and BID (in total 1600 mg) from C1D3 onward for the remaining 19 days of Cycle 1. For subsequent cycles, study drug was administered twice daily for 21 days each Cycle.
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* For dose escalation: Participants with any type of solid tumor (all comer) were eligible for dose escalation and dose expansion at MTD in Part 1; Participants enrolled for dose expansion (MTD expansion cohort all comer) were stratified according to high fibroblast growth factor receptor (FGFR) expression levels / FGFR mutation using archival or fresh tumor biopsy material * For expansion cohorts: Participants were eligible for Part 2 only if they have histological or cytological confirmed squamous non-small cell lung cancer (sqNSCLC), lung adenocarcinoma, head and neck cancer or bladder cancer (BC). All participants in Part 2 were stratified according to high FGFR expression levels FGFR mutation using archival or fresh tumor biopsy specimen. BC participants with low overall FGFR expression levels could be included if activating FGFR3 (FGFR tyrosine kinases 3) mutations were confirmed * Participants must have measurable disease (Response evaluation criteria in solid tumors (RECIST 1.1)) * Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 2 * Bone marrow, liver and renal functions as assessed by adequate laboratory methods to be conducted within 7 days prior to starting study Treatment * Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m\^2 according to the modified diet in renal disease (MDRD) abbreviated formula
Exclusion criteria
* Previous treatment with anti-FGFR directed therapies (e.g. receptor tyrosine kinase inhibitors or FGFR-specific antibodies) * Concomitant therapies that cannot be discontinued or switched to a different medication prior to study entry that are known to increase serum phosphate levels are not permitted within 4 weeks prior to start of study treatment) * Anticancer chemotherapy or immunotherapy during the study or within 5-halflives prior to start of study treatment. Mitomycin C, nitrosoureas or monoclonal antibodies with anticancer activity (e.g. bevacizumab or cetuximab etc.) should not be given within 6 weeks before starting to receive study treatment or within 6 weeks of pre-treatment biopsy for biomarker (p-ERK1/2) studies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| %AE,ur(12-24) (Amount of Drug Excreted Via Urine During the Collection Interval 12 - 24 Hours Post Administration) of BAY1163877 | On Cycle1, Day 1 | %AE,ur(12-24) (amount of drug excreted via urine during the collection interval 12 - 24 hours post administration, also expressed as percent of dose administered) of BAY1163877. |
| Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2) | Maximum drug concentration in plasma divided by dose (Cmax/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1) | Area under the plasma concentration vs time curve from time zero to 12 hours divided by dose (AUC(0-12)/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2) | Area under the plasma concentration vs time curve from time zero to 12 hours divided by dose (AUC(0-12)/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1) | Area under the plasma concentration vs time curve from time zero to the last data point \> LLOQ divided by dose (AUC(0-tlast)/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2) | Area under the plasma concentration vs time curve from time zero to the last data point \> LLOQ divided by dose (AUC(0-tlast)/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1) | AUC divided by dose (AUC/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2) | AUC divided by dose (AUC/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| Cmax,md (Cmax After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose | Cmax,md (Cmax after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| Cmax/Dmd (Cmax Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose | Cmax/Dmd (Cmax divided by dose after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| AUC(0-12)md (AUC(0-12) After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose | AUC(0-12)md (AUC(0-12) after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| AUC(0-12)/Dmd (AUC(0-12) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose | AUC(0-12)/Dmd (AUC(0-12) divided by dose after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| AUC(0-tlast)md (AUC(0-tlast) After Multiple Dose Administration) of BAY1163877 on Cycle 1, Day 15 | pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose | AUC(0-tlast)md (AUC(0-tlast) after multiple dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| AUC(0-tlast)/Dmd (AUC(0-tlast) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose | AUC(0-tlast)/Dmd (AUC(0-tlast) divided by dose after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| %AE,ur(0-12) (Amount of Drug Excreted Via Urine During the Collection Interval 0 - 12 Hours Post Administration) of BAY1163877 | On Cycle1, Day 1 | %AE,ur(0-12) (amount of drug excreted via urine during the collection interval 0 - 12 hours post administration, also expressed as percent of dose administered) of BAY1163877. |
| %AE,ur(0-24) (Amount of Drug Excreted Via Urine During the Collection Interval 0 - 24 Hours Post Administration) of BAY1163877 | On Cycle1, Day 1 | %AE,ur(0-24) (amount of drug excreted via urine during the collection interval 0 - 24 hours post administration, also expressed as percent of dose administered) of BAY1163877. |
| Maximum Tolerated Dose (MTD), Defined as Maximum Dose at Which the Incidence of Dose Limiting Toxicities (DLTs) During Cycle 1 is Below 20% | Up to 21 days | The MTD was defined as maximum dose at which the incidence of Dose Limiting Toxicities (DLTs) during Cycle 1 is below 20%. DLT was defined as any of the pre-defined adverse events occurring during Cycle 1 of a dose level and regarded by the investigators and/or sponsor to be related to the investigational drug. BID=twice daily. |
| Number of DLTs During Cycle 1 | Up to 21 days | DLT was defined as any of the pre-defined adverse events occurring during Cycle 1 of a dose level and regarded by the investigators and/or sponsor to be related to the investigational drug. |
| Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1) | Maximum drug concentration in plasma (Cmax) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2) | Maximum drug concentration in plasma (Cmax) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1) | Area under the plasma concentration vs time curve from time zero to 12 hours (AUC(0-12)) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2) | Area under the plasma concentration vs time curve from time zero to 12 hours (AUC(0-12)) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1) | Area under the plasma concentration vs time curve from time zero to the last data point \> LLOQ \[lower limit of quantification\] (AUC(0-tlast)) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2) | Area under the plasma concentration vs time curve from time zero to the last data point \> LLOQ \[lower limit of quantification\] (AUC(0-tlast)) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1) | Area under the plasma concentration vs time curve from zero to infinity (AUC) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2) | Area under the plasma concentration vs time curve from zero to infinity (AUC) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1) | Maximum drug concentration in plasma divided by dose (Cmax/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Up to 2 years | PFS was defined as the time (days) from the date of the first dose of study drug to the date of the first observed disease progression (radiological or clinical) or death due to any cause, if death occurred before progression was documented. PFS for participants without tumor progression at the time of analysis was censored at their last date of tumor evaluation. |
| Time to Progression (TTP) | Up to 2 years | TTP was defined as the time from start of study treatment until first observed disease progression (radiological or clinical). Progression is defined using RECIST v1.0, as at least a 20% increase in the sum of diameters of the target lesions, taking as a references the smallest sum on study. |
| Duration of Response (DOR) | Up to 2 years | DOR (for partial and complete response (PR/CR)) was defined as the time (days) from the first documented objective response of PR or CR, whichever was noted earlier, to disease progression or death (if death occurred before progression was documented). DOR was calculated for responders only, i.e. participants with complete or partial response. Therefore, the dose escalation group is not displayed. |
| Duration of Treatment (DOT) | Up to 2 years | — |
| Evaluation of Biomarker Status -Change in Serum FGF23 (Fibroblast Growth Factor 23) Levels From Baseline to C2D1 | From baseline to C2D1 | Change in serum FGF23 levels from baseline to C2D1 was reported as ratio to baseline (%). |
| Evaluation of Pharmacodynamic Parameters (PD) - Change of Heart Rate (HR) From Baseline to End of Study | From baseline up to 2 years | — |
| Evaluation of Pharmacodynamic Parameters (PD) - Change of Blood Pressure (BP) From Baseline to End of Study | From baseline up to 2 years | — |
| Evaluation of Pharmacodynamic Parameters (PD) - Change of QT Intervals From Baseline up to Cycle 1, Day 15 | From baseline up to Cycle 1, Day 15 | — |
| Evaluation of Relative Bioavailability of the Tablet Formulation in Comparison to the Solution Formulation of BAY1163877 | On Cycle 1, Day -3 and Cycle 1, Day 1 | In order to evaluate the relative bioavailability of the tablet formulation, tablet Cmax/D, AUC(0-tlast)/D, and AUC/D on Cycle 1, Day -3 were compared to solution Cmax/D, AUC(0-tlast)/D, AUC/D on Cycle 1, Day 1 for all analytes. The logarithms of the PK parameters were analyzed using analysis of variance (ANOVA) including participant and formulation effects. Based on these analyses, point estimates (LS-means) and exploratory 90% confidence intervals for the ratios (tablet/solution) of Cmax/D, AUC(0- tlast)/D, and AUC/D were calculated by re-transformation of the logarithmic data using the intra-individual standard deviation of the ANOVA. |
| Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hour(s) post-dose | Tmax (time to reach maximum drug concentration in plasma) of BAY1163877 after single dose administration on Cycle 1, Day -3 and Cycle 1, Day 1. Median and full range were reported. |
| Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hour(s) post-dose | Tlast (time of last plasma concentration above LLOQ) of BAY1163877 after single dose administration on Cycle 1, Day -3 and Cycle 1, Day 1. Median and full range were reported. |
| T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hour(s) post-dose | T1/2 (half-life associated with the terminal slope) of BAY1163877 after single dose administration on Cycle 1, Day -3 and Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. |
| Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose | Tmax,md (time to reach maximum drug concentration in plasma after multiple-dose administration) of BAY1163877. Median and full range were reported. |
| Tlast,md (Time of Last Plasma Concentration Above LLOQ After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose | Tlast,md (time of last plasma concentration above LLOQ after multiple-dose administration) of BAY1163877. Median and full range were reported. |
| Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | Up to 2 years | Response as defined by RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1: complete response (CR: disappearance of all target lesions), partial response (PR: at least a 30% decrease in the sum of diameters of target lesions taking as the reference the baseline sum of diameters), stable disease (SD: steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as a reference, the smallest sum of diameters while in the trial), progressive disease (PD: at least a 20% increase in the sum of diameters of the target lesions, taking as a references the smallest sum on study). |
Countries
France, Germany, Singapore, South Korea, Spain, Switzerland, United States
Participant flow
Recruitment details
Study was conducted at 29 centers in 7 countries, between 30 Dec 2013 (first subject first visit) and 27 Nov 2019 (last subject last visit).
Pre-assignment details
A total of 988 participants were screened, of whom 168 participants were assigned into the study and received at least one dose of study medication.
Participants by arm
| Arm | Count |
|---|---|
| Rogaratinib 50 mg BID Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase. | 4 |
| Rogaratinib 100 mg BID Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase. | 4 |
| Rogaratinib 200 mg BID Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase. | 4 |
| Rogaratinib 400 mg BID Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase. | 3 |
| Rogaratinib 600 mg BID Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase. | 4 |
| Rogaratinib 800 mg BID Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase. | 4 |
| Rogaratinib Dose Expansion (All Comers) Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles. | 23 |
| Rogaratinib Dose Expansion (BC) Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles. | 74 |
| Rogaratinib Dose Expansion (SCCHN) Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles. | 8 |
| Rogaratinib Dose Expansion (sqNSCLC) Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles. | 40 |
| Total | 168 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 2 | 0 | 0 | 0 | 3 | 8 | 1 | 4 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 4 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Rogaratinib Dose Expansion (sqNSCLC) | Rogaratinib Dose Expansion (SCCHN) | Rogaratinib Dose Expansion (BC) | Rogaratinib Dose Expansion (All Comers) | Rogaratinib 800 mg BID | Rogaratinib 600 mg BID | Rogaratinib 400 mg BID | Rogaratinib 200 mg BID | Rogaratinib 100 mg BID | Rogaratinib 50 mg BID |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 63.6 Years STANDARD_DEVIATION 9.3 | 62.6 Years STANDARD_DEVIATION 6.6 | 63.4 Years STANDARD_DEVIATION 11.1 | 66.4 Years STANDARD_DEVIATION 8.6 | 63.0 Years STANDARD_DEVIATION 7.8 | 64.3 Years STANDARD_DEVIATION 8.4 | 56.8 Years STANDARD_DEVIATION 12.9 | 56.3 Years STANDARD_DEVIATION 9.8 | 55.8 Years STANDARD_DEVIATION 15.3 | 58.5 Years STANDARD_DEVIATION 12.4 | 52.5 Years STANDARD_DEVIATION 20.4 |
| Eastern Cooperative Oncology Group (ECOG) Performance status ECOG=0 | 56 Participants | 14 Participants | 3 Participants | 20 Participants | 10 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance status ECOG=1 | 100 Participants | 22 Participants | 5 Participants | 49 Participants | 12 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance status ECOG=2 | 12 Participants | 4 Participants | 0 Participants | 5 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 149 Participants | 34 Participants | 8 Participants | 61 Participants | 23 Participants | 4 Participants | 4 Participants | 3 Participants | 4 Participants | 4 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 18 Participants | 6 Participants | 0 Participants | 12 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 37 Participants | 11 Participants | 1 Participants | 13 Participants | 8 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 18 Participants | 7 Participants | 0 Participants | 11 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 113 Participants | 22 Participants | 7 Participants | 50 Participants | 15 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 4 Participants | 4 Participants |
| Sex: Female, Male Female | 46 Participants | 8 Participants | 0 Participants | 20 Participants | 9 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 122 Participants | 32 Participants | 8 Participants | 54 Participants | 14 Participants | 4 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 23 | 6 / 23 | 17 / 74 | 2 / 8 | 12 / 40 |
| other Total, other adverse events | 22 / 23 | 23 / 23 | 73 / 74 | 8 / 8 | 40 / 40 |
| serious Total, serious adverse events | 9 / 23 | 14 / 23 | 44 / 74 | 5 / 8 | 24 / 40 |
Outcome results
Primary
%AE,ur(0-12) (Amount of Drug Excreted Via Urine During the Collection Interval 0 - 12 Hours Post Administration) of BAY1163877
%AE,ur(0-12) (amount of drug excreted via urine during the collection interval 0 - 12 hours post administration, also expressed as percent of dose administered) of BAY1163877.
Time frame: On Cycle1, Day 1
Population: Urine interval samples on C1D1 were collected in a subgroup of subjects from the 800 mg BID expansion part.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rogaratinib Total Dose Escalation | %AE,ur(0-12) (Amount of Drug Excreted Via Urine During the Collection Interval 0 - 12 Hours Post Administration) of BAY1163877 | 0.164 percentage |
Primary
%AE,ur(0-24) (Amount of Drug Excreted Via Urine During the Collection Interval 0 - 24 Hours Post Administration) of BAY1163877
%AE,ur(0-24) (amount of drug excreted via urine during the collection interval 0 - 24 hours post administration, also expressed as percent of dose administered) of BAY1163877.
Time frame: On Cycle1, Day 1
Population: Urine interval samples on C1D1 were collected in a subgroup of subjects from the 800 mg BID expansion part.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rogaratinib Total Dose Escalation | %AE,ur(0-24) (Amount of Drug Excreted Via Urine During the Collection Interval 0 - 24 Hours Post Administration) of BAY1163877 | 0.180 percentage |
Primary
%AE,ur(12-24) (Amount of Drug Excreted Via Urine During the Collection Interval 12 - 24 Hours Post Administration) of BAY1163877
%AE,ur(12-24) (amount of drug excreted via urine during the collection interval 12 - 24 hours post administration, also expressed as percent of dose administered) of BAY1163877.
Time frame: On Cycle1, Day 1
Population: Urine interval samples on C1D1 were collected in a subgroup of subjects from the 800 mg BID expansion part.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rogaratinib Total Dose Escalation | %AE,ur(12-24) (Amount of Drug Excreted Via Urine During the Collection Interval 12 - 24 Hours Post Administration) of BAY1163877 | 0.0224 percentage |
Primary
AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Area under the plasma concentration vs time curve from time zero to 12 hours (AUC(0-12)) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Population: All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 12100 µg*h/L | Geometric Coefficient of Variation 16.3 |
| Rogaratinib Expansion Food Effect | AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 15300 µg*h/L | Geometric Coefficient of Variation 41.4 |
| Rogaratinib 200 mg BID | AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 33200 µg*h/L | Geometric Coefficient of Variation 33.1 |
| Rogaratinib 400 mg BID | AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 44000 µg*h/L | Geometric Coefficient of Variation 68.9 |
| Rogaratinib 600 mg BID | AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 54300 µg*h/L | Geometric Coefficient of Variation 31.3 |
| Rogaratinib 800 mg BID | AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 55700 µg*h/L | Geometric Coefficient of Variation 43.5 |
| Rogaratinib 800 mg BID Pooled | AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 63900 µg*h/L | Geometric Coefficient of Variation 45 |
| Rogaratinib Expansion Food Effect | AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 74200 µg*h/L | Geometric Coefficient of Variation 49.7 |
| Rogaratinib Dose Expansion (All Comers) | AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 63700 µg*h/L | Geometric Coefficient of Variation 46.5 |
| Rogaratinib Dose Expansion (BC) | AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 59700 µg*h/L | Geometric Coefficient of Variation 56.4 |
| Rogaratinib Dose Expansion (SCCHN) | AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 101000 µg*h/L | Geometric Coefficient of Variation 37.4 |
| Rogaratinib Dose Expansion (sqNSCLC) | AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 66700 µg*h/L | Geometric Coefficient of Variation 32 |
Primary
AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Area under the plasma concentration vs time curve from time zero to 12 hours (AUC(0-12)) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Population: All participants with valid PK data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | 15600 µg*h/L | Geometric Coefficient of Variation 72 |
| Rogaratinib Expansion Food Effect | AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | 71000 µg*h/L | Geometric Coefficient of Variation 42.7 |
Primary
AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Area under the plasma concentration vs time curve from time zero to 12 hours divided by dose (AUC(0-12)/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Population: All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.242 h/L | Geometric Coefficient of Variation 16.3 |
| Rogaratinib Expansion Food Effect | AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.153 h/L | Geometric Coefficient of Variation 41.4 |
| Rogaratinib 200 mg BID | AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.166 h/L | Geometric Coefficient of Variation 33.1 |
| Rogaratinib 400 mg BID | AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.110 h/L | Geometric Coefficient of Variation 68.9 |
| Rogaratinib 600 mg BID | AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.0906 h/L | Geometric Coefficient of Variation 31.1 |
| Rogaratinib 800 mg BID | AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.0696 h/L | Geometric Coefficient of Variation 43.5 |
| Rogaratinib 800 mg BID Pooled | AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.0798 h/L | Geometric Coefficient of Variation 45 |
| Rogaratinib Expansion Food Effect | AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.0927 h/L | Geometric Coefficient of Variation 49.7 |
| Rogaratinib Dose Expansion (All Comers) | AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.0796 h/L | Geometric Coefficient of Variation 46.5 |
| Rogaratinib Dose Expansion (BC) | AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.0747 h/L | Geometric Coefficient of Variation 56.4 |
| Rogaratinib Dose Expansion (SCCHN) | AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.126 h/L | Geometric Coefficient of Variation 37.4 |
| Rogaratinib Dose Expansion (sqNSCLC) | AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.0834 h/L | Geometric Coefficient of Variation 32 |
Primary
AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Area under the plasma concentration vs time curve from time zero to 12 hours divided by dose (AUC(0-12)/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Population: All participants with valid PK data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | 0.156 h/L | Geometric Coefficient of Variation 72 |
| Rogaratinib Expansion Food Effect | AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | 0.0888 h/L | Geometric Coefficient of Variation 42.7 |
Primary
AUC(0-12)/Dmd (AUC(0-12) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
AUC(0-12)/Dmd (AUC(0-12) divided by dose after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Population: All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | AUC(0-12)/Dmd (AUC(0-12) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.266 h/L | Geometric Coefficient of Variation 75.4 |
| Rogaratinib Expansion Food Effect | AUC(0-12)/Dmd (AUC(0-12) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.215 h/L | Geometric Coefficient of Variation 98.5 |
| Rogaratinib 200 mg BID | AUC(0-12)/Dmd (AUC(0-12) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.209 h/L | Geometric Coefficient of Variation 27.9 |
| Rogaratinib 400 mg BID | AUC(0-12)/Dmd (AUC(0-12) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.153 h/L | Geometric Coefficient of Variation 66.2 |
| Rogaratinib 600 mg BID | AUC(0-12)/Dmd (AUC(0-12) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.123 h/L | Geometric Coefficient of Variation 33.4 |
| Rogaratinib 800 mg BID | AUC(0-12)/Dmd (AUC(0-12) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.114 h/L | Geometric Coefficient of Variation 28.8 |
| Rogaratinib 800 mg BID Pooled | AUC(0-12)/Dmd (AUC(0-12) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.107 h/L | Geometric Coefficient of Variation 42.8 |
| Rogaratinib Expansion Food Effect | AUC(0-12)/Dmd (AUC(0-12) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.109 h/L | Geometric Coefficient of Variation 28.5 |
| Rogaratinib Dose Expansion (All Comers) | AUC(0-12)/Dmd (AUC(0-12) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.102 h/L | Geometric Coefficient of Variation 44.5 |
| Rogaratinib Dose Expansion (BC) | AUC(0-12)/Dmd (AUC(0-12) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.106 h/L | Geometric Coefficient of Variation 40.8 |
| Rogaratinib Dose Expansion (SCCHN) | AUC(0-12)/Dmd (AUC(0-12) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.132 h/L | — |
| Rogaratinib Dose Expansion (sqNSCLC) | AUC(0-12)/Dmd (AUC(0-12) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.109 h/L | Geometric Coefficient of Variation 49.1 |
Primary
AUC(0-12)md (AUC(0-12) After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
AUC(0-12)md (AUC(0-12) after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Population: All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | AUC(0-12)md (AUC(0-12) After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 13300 µg*h/L | Geometric Coefficient of Variation 75.4 |
| Rogaratinib Expansion Food Effect | AUC(0-12)md (AUC(0-12) After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 21500 µg*h/L | Geometric Coefficient of Variation 98.5 |
| Rogaratinib 200 mg BID | AUC(0-12)md (AUC(0-12) After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 41700 µg*h/L | Geometric Coefficient of Variation 27.9 |
| Rogaratinib 400 mg BID | AUC(0-12)md (AUC(0-12) After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 61100 µg*h/L | Geometric Coefficient of Variation 66.2 |
| Rogaratinib 600 mg BID | AUC(0-12)md (AUC(0-12) After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 73500 µg*h/L | Geometric Coefficient of Variation 33.4 |
| Rogaratinib 800 mg BID | AUC(0-12)md (AUC(0-12) After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 90900 µg*h/L | Geometric Coefficient of Variation 28.8 |
| Rogaratinib 800 mg BID Pooled | AUC(0-12)md (AUC(0-12) After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 85300 µg*h/L | Geometric Coefficient of Variation 42.8 |
| Rogaratinib Expansion Food Effect | AUC(0-12)md (AUC(0-12) After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 87100 µg*h/L | Geometric Coefficient of Variation 28.5 |
| Rogaratinib Dose Expansion (All Comers) | AUC(0-12)md (AUC(0-12) After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 81700 µg*h/L | Geometric Coefficient of Variation 44.5 |
| Rogaratinib Dose Expansion (BC) | AUC(0-12)md (AUC(0-12) After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 84500 µg*h/L | Geometric Coefficient of Variation 40.8 |
| Rogaratinib Dose Expansion (SCCHN) | AUC(0-12)md (AUC(0-12) After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 106000 µg*h/L | — |
| Rogaratinib Dose Expansion (sqNSCLC) | AUC(0-12)md (AUC(0-12) After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 87100 µg*h/L | Geometric Coefficient of Variation 49.1 |
Primary
AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Area under the plasma concentration vs time curve from time zero to the last data point \> LLOQ \[lower limit of quantification\] (AUC(0-tlast)) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Population: All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 14200 µg*h/L | Geometric Coefficient of Variation 24.4 |
| Rogaratinib Expansion Food Effect | AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 20100 µg*h/L | Geometric Coefficient of Variation 57.7 |
| Rogaratinib 200 mg BID | AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 43800 µg*h/L | Geometric Coefficient of Variation 36.3 |
| Rogaratinib 400 mg BID | AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 62000 µg*h/L | Geometric Coefficient of Variation 114 |
| Rogaratinib 600 mg BID | AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 78000 µg*h/L | Geometric Coefficient of Variation 38.5 |
| Rogaratinib 800 mg BID | AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 86600 µg*h/L | Geometric Coefficient of Variation 41.2 |
| Rogaratinib 800 mg BID Pooled | AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 103000 µg*h/L | Geometric Coefficient of Variation 53.5 |
| Rogaratinib Expansion Food Effect | AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 121000 µg*h/L | Geometric Coefficient of Variation 49.3 |
| Rogaratinib Dose Expansion (All Comers) | AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 104000 µg*h/L | Geometric Coefficient of Variation 73.4 |
| Rogaratinib Dose Expansion (BC) | AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 108000 µg*h/L | Geometric Coefficient of Variation 33.8 |
| Rogaratinib Dose Expansion (SCCHN) | AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 172000 µg*h/L | Geometric Coefficient of Variation 55.3 |
| Rogaratinib Dose Expansion (sqNSCLC) | AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 94900 µg*h/L | Geometric Coefficient of Variation 39.6 |
Primary
AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Area under the plasma concentration vs time curve from time zero to the last data point \> LLOQ \[lower limit of quantification\] (AUC(0-tlast)) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Population: All participants with valid PK data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | 20000 µg*h/L | Geometric Coefficient of Variation 87.3 |
| Rogaratinib Expansion Food Effect | AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | 99300 µg*h/L | Geometric Coefficient of Variation 52.9 |
Primary
AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Area under the plasma concentration vs time curve from time zero to the last data point \> LLOQ divided by dose (AUC(0-tlast)/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Population: All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.283 h/L | Geometric Coefficient of Variation 24.4 |
| Rogaratinib Expansion Food Effect | AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.201 h/L | Geometric Coefficient of Variation 57.7 |
| Rogaratinib 200 mg BID | AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.219 h/L | Geometric Coefficient of Variation 36.3 |
| Rogaratinib 400 mg BID | AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.155 h/L | Geometric Coefficient of Variation 114 |
| Rogaratinib 600 mg BID | AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.130 h/L | Geometric Coefficient of Variation 38.5 |
| Rogaratinib 800 mg BID | AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.108 h/L | Geometric Coefficient of Variation 41.2 |
| Rogaratinib 800 mg BID Pooled | AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.129 h/L | Geometric Coefficient of Variation 53.5 |
| Rogaratinib Expansion Food Effect | AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.152 h/L | Geometric Coefficient of Variation 49.3 |
| Rogaratinib Dose Expansion (All Comers) | AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.130 h/L | Geometric Coefficient of Variation 73.4 |
| Rogaratinib Dose Expansion (BC) | AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.135 h/L | Geometric Coefficient of Variation 33.8 |
| Rogaratinib Dose Expansion (SCCHN) | AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.215 h/L | Geometric Coefficient of Variation 55.3 |
| Rogaratinib Dose Expansion (sqNSCLC) | AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.119 h/L | Geometric Coefficient of Variation 39.6 |
Primary
AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Area under the plasma concentration vs time curve from time zero to the last data point \> LLOQ divided by dose (AUC(0-tlast)/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Population: All participants with valid PK data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | 0.200 h/L | Geometric Coefficient of Variation 87.3 |
| Rogaratinib Expansion Food Effect | AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | 0.124 h/L | Geometric Coefficient of Variation 52.9 |
Primary
AUC(0-tlast)/Dmd (AUC(0-tlast) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
AUC(0-tlast)/Dmd (AUC(0-tlast) divided by dose after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Population: All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | AUC(0-tlast)/Dmd (AUC(0-tlast) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.250 h/L | Geometric Coefficient of Variation 78.5 |
| Rogaratinib Expansion Food Effect | AUC(0-tlast)/Dmd (AUC(0-tlast) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.215 h/L | Geometric Coefficient of Variation 99.8 |
| Rogaratinib 200 mg BID | AUC(0-tlast)/Dmd (AUC(0-tlast) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.196 h/L | Geometric Coefficient of Variation 19.1 |
| Rogaratinib 400 mg BID | AUC(0-tlast)/Dmd (AUC(0-tlast) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.151 h/L | Geometric Coefficient of Variation 65.8 |
| Rogaratinib 600 mg BID | AUC(0-tlast)/Dmd (AUC(0-tlast) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.121 h/L | Geometric Coefficient of Variation 33.3 |
| Rogaratinib 800 mg BID | AUC(0-tlast)/Dmd (AUC(0-tlast) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.111 h/L | Geometric Coefficient of Variation 30.9 |
| Rogaratinib 800 mg BID Pooled | AUC(0-tlast)/Dmd (AUC(0-tlast) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.102 h/L | Geometric Coefficient of Variation 43.4 |
| Rogaratinib Expansion Food Effect | AUC(0-tlast)/Dmd (AUC(0-tlast) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.105 h/L | Geometric Coefficient of Variation 31.3 |
| Rogaratinib Dose Expansion (All Comers) | AUC(0-tlast)/Dmd (AUC(0-tlast) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.0937 h/L | Geometric Coefficient of Variation 44.3 |
| Rogaratinib Dose Expansion (BC) | AUC(0-tlast)/Dmd (AUC(0-tlast) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.105 h/L | Geometric Coefficient of Variation 40.8 |
| Rogaratinib Dose Expansion (SCCHN) | AUC(0-tlast)/Dmd (AUC(0-tlast) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.129 h/L | — |
| Rogaratinib Dose Expansion (sqNSCLC) | AUC(0-tlast)/Dmd (AUC(0-tlast) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.102 h/L | Geometric Coefficient of Variation 50.1 |
Primary
AUC(0-tlast)md (AUC(0-tlast) After Multiple Dose Administration) of BAY1163877 on Cycle 1, Day 15
AUC(0-tlast)md (AUC(0-tlast) after multiple dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Population: All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | AUC(0-tlast)md (AUC(0-tlast) After Multiple Dose Administration) of BAY1163877 on Cycle 1, Day 15 | 12500 µg*h/L | Geometric Coefficient of Variation 78.5 |
| Rogaratinib Expansion Food Effect | AUC(0-tlast)md (AUC(0-tlast) After Multiple Dose Administration) of BAY1163877 on Cycle 1, Day 15 | 21500 µg*h/L | Geometric Coefficient of Variation 99.8 |
| Rogaratinib 200 mg BID | AUC(0-tlast)md (AUC(0-tlast) After Multiple Dose Administration) of BAY1163877 on Cycle 1, Day 15 | 39200 µg*h/L | Geometric Coefficient of Variation 19.1 |
| Rogaratinib 400 mg BID | AUC(0-tlast)md (AUC(0-tlast) After Multiple Dose Administration) of BAY1163877 on Cycle 1, Day 15 | 60200 µg*h/L | Geometric Coefficient of Variation 65.8 |
| Rogaratinib 600 mg BID | AUC(0-tlast)md (AUC(0-tlast) After Multiple Dose Administration) of BAY1163877 on Cycle 1, Day 15 | 72500 µg*h/L | Geometric Coefficient of Variation 33.3 |
| Rogaratinib 800 mg BID | AUC(0-tlast)md (AUC(0-tlast) After Multiple Dose Administration) of BAY1163877 on Cycle 1, Day 15 | 89000 µg*h/L | Geometric Coefficient of Variation 30.9 |
| Rogaratinib 800 mg BID Pooled | AUC(0-tlast)md (AUC(0-tlast) After Multiple Dose Administration) of BAY1163877 on Cycle 1, Day 15 | 81500 µg*h/L | Geometric Coefficient of Variation 43.4 |
| Rogaratinib Expansion Food Effect | AUC(0-tlast)md (AUC(0-tlast) After Multiple Dose Administration) of BAY1163877 on Cycle 1, Day 15 | 84100 µg*h/L | Geometric Coefficient of Variation 31.3 |
| Rogaratinib Dose Expansion (All Comers) | AUC(0-tlast)md (AUC(0-tlast) After Multiple Dose Administration) of BAY1163877 on Cycle 1, Day 15 | 75000 µg*h/L | Geometric Coefficient of Variation 44.3 |
| Rogaratinib Dose Expansion (BC) | AUC(0-tlast)md (AUC(0-tlast) After Multiple Dose Administration) of BAY1163877 on Cycle 1, Day 15 | 83600 µg*h/L | Geometric Coefficient of Variation 40.8 |
| Rogaratinib Dose Expansion (SCCHN) | AUC(0-tlast)md (AUC(0-tlast) After Multiple Dose Administration) of BAY1163877 on Cycle 1, Day 15 | 103000 µg*h/L | — |
| Rogaratinib Dose Expansion (sqNSCLC) | AUC(0-tlast)md (AUC(0-tlast) After Multiple Dose Administration) of BAY1163877 on Cycle 1, Day 15 | 81300 µg*h/L | Geometric Coefficient of Variation 50.1 |
Primary
AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Area under the plasma concentration vs time curve from zero to infinity (AUC) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Population: All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 14300 µg*h/L | Geometric Coefficient of Variation 24.5 |
| Rogaratinib Expansion Food Effect | AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 20700 µg*h/L | Geometric Coefficient of Variation 58.1 |
| Rogaratinib 200 mg BID | AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 44300 µg*h/L | Geometric Coefficient of Variation 37.1 |
| Rogaratinib 400 mg BID | AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 64000 µg*h/L | Geometric Coefficient of Variation 118 |
| Rogaratinib 600 mg BID | AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 79800 µg*h/L | Geometric Coefficient of Variation 39.5 |
| Rogaratinib 800 mg BID | AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 95400 µg*h/L | Geometric Coefficient of Variation 48.7 |
| Rogaratinib 800 mg BID Pooled | AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 109000 µg*h/L | Geometric Coefficient of Variation 58.4 |
| Rogaratinib Expansion Food Effect | AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 133000 µg*h/L | Geometric Coefficient of Variation 53.3 |
| Rogaratinib Dose Expansion (All Comers) | AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 109000 µg*h/L | Geometric Coefficient of Variation 77.5 |
| Rogaratinib Dose Expansion (BC) | AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 115000 µg*h/L | Geometric Coefficient of Variation 38.9 |
| Rogaratinib Dose Expansion (SCCHN) | AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 191000 µg*h/L | Geometric Coefficient of Variation 69.9 |
| Rogaratinib Dose Expansion (sqNSCLC) | AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 99600 µg*h/L | Geometric Coefficient of Variation 46.5 |
Primary
AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Area under the plasma concentration vs time curve from zero to infinity (AUC) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Population: All participants with valid PK data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | 20200 µg*h/L | Geometric Coefficient of Variation 87.1 |
| Rogaratinib Expansion Food Effect | AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | 102000 µg*h/L | Geometric Coefficient of Variation 55.2 |
Primary
AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
AUC divided by dose (AUC/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Population: All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.286 h/L | Geometric Coefficient of Variation 24.5 |
| Rogaratinib Expansion Food Effect | AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.207 h/L | Geometric Coefficient of Variation 58.1 |
| Rogaratinib 200 mg BID | AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.221 h/L | Geometric Coefficient of Variation 37.1 |
| Rogaratinib 400 mg BID | AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.160 h/L | Geometric Coefficient of Variation 118 |
| Rogaratinib 600 mg BID | AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.133 h/L | Geometric Coefficient of Variation 39.5 |
| Rogaratinib 800 mg BID | AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.119 h/L | Geometric Coefficient of Variation 48.7 |
| Rogaratinib 800 mg BID Pooled | AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.137 h/L | Geometric Coefficient of Variation 58.4 |
| Rogaratinib Expansion Food Effect | AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.166 h/L | Geometric Coefficient of Variation 53.3 |
| Rogaratinib Dose Expansion (All Comers) | AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.136 h/L | Geometric Coefficient of Variation 77.5 |
| Rogaratinib Dose Expansion (BC) | AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.144 h/L | Geometric Coefficient of Variation 38.9 |
| Rogaratinib Dose Expansion (SCCHN) | AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.239 h/L | Geometric Coefficient of Variation 69.9 |
| Rogaratinib Dose Expansion (sqNSCLC) | AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.124 h/L | Geometric Coefficient of Variation 46.5 |
Primary
AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
AUC divided by dose (AUC/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Population: All participants with valid PK data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | 0.202 h/L | Geometric Coefficient of Variation 87.1 |
| Rogaratinib Expansion Food Effect | AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | 0.127 h/L | Geometric Coefficient of Variation 55.2 |
Primary
Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Maximum drug concentration in plasma divided by dose (Cmax/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Population: All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.0728 /L | Geometric Coefficient of Variation 16.8 |
| Rogaratinib Expansion Food Effect | Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.0436 /L | Geometric Coefficient of Variation 36.4 |
| Rogaratinib 200 mg BID | Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.0282 /L | Geometric Coefficient of Variation 46.2 |
| Rogaratinib 400 mg BID | Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.0237 /L | Geometric Coefficient of Variation 16.1 |
| Rogaratinib 600 mg BID | Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.0151 /L | Geometric Coefficient of Variation 32.3 |
| Rogaratinib 800 mg BID | Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.0127 /L | Geometric Coefficient of Variation 17.3 |
| Rogaratinib 800 mg BID Pooled | Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.0138 /L | Geometric Coefficient of Variation 34.3 |
| Rogaratinib Expansion Food Effect | Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.0137 /L | Geometric Coefficient of Variation 47.6 |
| Rogaratinib Dose Expansion (All Comers) | Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.0137 /L | Geometric Coefficient of Variation 32.5 |
| Rogaratinib Dose Expansion (BC) | Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.0137 /L | Geometric Coefficient of Variation 48.1 |
| Rogaratinib Dose Expansion (SCCHN) | Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.0174 /L | Geometric Coefficient of Variation 52.6 |
| Rogaratinib Dose Expansion (sqNSCLC) | Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 0.0140 /L | Geometric Coefficient of Variation 26 |
Primary
Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Maximum drug concentration in plasma divided by dose (Cmax/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Population: All participants with valid PK data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | 0.0276 /L | Geometric Coefficient of Variation 56.5 |
| Rogaratinib Expansion Food Effect | Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | 0.0141 /L | Geometric Coefficient of Variation 33.8 |
Primary
Cmax/Dmd (Cmax Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
Cmax/Dmd (Cmax divided by dose after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Population: All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | Cmax/Dmd (Cmax Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.0789 /L | Geometric Coefficient of Variation 38.5 |
| Rogaratinib Expansion Food Effect | Cmax/Dmd (Cmax Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.0487 /L | Geometric Coefficient of Variation 35.2 |
| Rogaratinib 200 mg BID | Cmax/Dmd (Cmax Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.0416 /L | Geometric Coefficient of Variation 68.9 |
| Rogaratinib 400 mg BID | Cmax/Dmd (Cmax Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.0237 /L | Geometric Coefficient of Variation 63.1 |
| Rogaratinib 600 mg BID | Cmax/Dmd (Cmax Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.0174 /L | Geometric Coefficient of Variation 32.6 |
| Rogaratinib 800 mg BID | Cmax/Dmd (Cmax Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.0155 /L | Geometric Coefficient of Variation 33.8 |
| Rogaratinib 800 mg BID Pooled | Cmax/Dmd (Cmax Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.0158 /L | Geometric Coefficient of Variation 34.6 |
| Rogaratinib Expansion Food Effect | Cmax/Dmd (Cmax Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.0138 /L | Geometric Coefficient of Variation 27.9 |
| Rogaratinib Dose Expansion (All Comers) | Cmax/Dmd (Cmax Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.0154 /L | Geometric Coefficient of Variation 31 |
| Rogaratinib Dose Expansion (BC) | Cmax/Dmd (Cmax Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.0163 /L | Geometric Coefficient of Variation 33.6 |
| Rogaratinib Dose Expansion (SCCHN) | Cmax/Dmd (Cmax Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.0163 /L | — |
| Rogaratinib Dose Expansion (sqNSCLC) | Cmax/Dmd (Cmax Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.0153 /L | Geometric Coefficient of Variation 40.5 |
Primary
Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Maximum drug concentration in plasma (Cmax) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Population: All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 3640 µg/L | Geometric Coefficient of Variation 16.8 |
| Rogaratinib Expansion Food Effect | Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 4360 µg/L | Geometric Coefficient of Variation 36.4 |
| Rogaratinib 200 mg BID | Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 5630 µg/L | Geometric Coefficient of Variation 46.2 |
| Rogaratinib 400 mg BID | Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 9480 µg/L | Geometric Coefficient of Variation 16.1 |
| Rogaratinib 600 mg BID | Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 9060 µg/L | Geometric Coefficient of Variation 32.3 |
| Rogaratinib 800 mg BID | Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 10200 µg/L | Geometric Coefficient of Variation 17.3 |
| Rogaratinib 800 mg BID Pooled | Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 11000 µg/L | Geometric Coefficient of Variation 34.3 |
| Rogaratinib Expansion Food Effect | Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 11000 µg/L | Geometric Coefficient of Variation 47.6 |
| Rogaratinib Dose Expansion (All Comers) | Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 10900 µg/L | Geometric Coefficient of Variation 32.5 |
| Rogaratinib Dose Expansion (BC) | Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 11000 µg/L | Geometric Coefficient of Variation 48.1 |
| Rogaratinib Dose Expansion (SCCHN) | Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 13900 µg/L | Geometric Coefficient of Variation 52.6 |
| Rogaratinib Dose Expansion (sqNSCLC) | Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1 | 11200 µg/L | Geometric Coefficient of Variation 26 |
Primary
Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Maximum drug concentration in plasma (Cmax) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Population: All participants with valid pharmacokinetic (PK) data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | 2760 µg/L | Geometric Coefficient of Variation 56.5 |
| Rogaratinib Expansion Food Effect | Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 | 11300 µg/L | Geometric Coefficient of Variation 33.8 |
Primary
Cmax,md (Cmax After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
Cmax,md (Cmax after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Population: All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | Cmax,md (Cmax After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 3940 µg/L | Geometric Coefficient of Variation 38.5 |
| Rogaratinib Expansion Food Effect | Cmax,md (Cmax After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 4870 µg/L | Geometric Coefficient of Variation 35.2 |
| Rogaratinib 200 mg BID | Cmax,md (Cmax After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 8320 µg/L | Geometric Coefficient of Variation 68.9 |
| Rogaratinib 400 mg BID | Cmax,md (Cmax After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 9490 µg/L | Geometric Coefficient of Variation 63.1 |
| Rogaratinib 600 mg BID | Cmax,md (Cmax After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 10500 µg/L | Geometric Coefficient of Variation 32.6 |
| Rogaratinib 800 mg BID | Cmax,md (Cmax After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 12400 µg/L | Geometric Coefficient of Variation 33.8 |
| Rogaratinib 800 mg BID Pooled | Cmax,md (Cmax After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 12600 µg/L | Geometric Coefficient of Variation 34.6 |
| Rogaratinib Expansion Food Effect | Cmax,md (Cmax After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 11000 µg/L | Geometric Coefficient of Variation 27.9 |
| Rogaratinib Dose Expansion (All Comers) | Cmax,md (Cmax After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 12300 µg/L | Geometric Coefficient of Variation 31 |
| Rogaratinib Dose Expansion (BC) | Cmax,md (Cmax After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 13100 µg/L | Geometric Coefficient of Variation 33.6 |
| Rogaratinib Dose Expansion (SCCHN) | Cmax,md (Cmax After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 13100 µg/L | — |
| Rogaratinib Dose Expansion (sqNSCLC) | Cmax,md (Cmax After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 12300 µg/L | Geometric Coefficient of Variation 40.5 |
Primary
Maximum Tolerated Dose (MTD), Defined as Maximum Dose at Which the Incidence of Dose Limiting Toxicities (DLTs) During Cycle 1 is Below 20%
The MTD was defined as maximum dose at which the incidence of Dose Limiting Toxicities (DLTs) during Cycle 1 is below 20%. DLT was defined as any of the pre-defined adverse events occurring during Cycle 1 of a dose level and regarded by the investigators and/or sponsor to be related to the investigational drug. BID=twice daily.
Time frame: Up to 21 days
Population: MTD evaluation set: All participants of the total dose-escalation group who completed Cycle 1 or discontinued during Cycle 1 due to an adverse event or DLT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rogaratinib Total Dose Escalation | Maximum Tolerated Dose (MTD), Defined as Maximum Dose at Which the Incidence of Dose Limiting Toxicities (DLTs) During Cycle 1 is Below 20% | 800 mg BID |
Primary
Number of DLTs During Cycle 1
DLT was defined as any of the pre-defined adverse events occurring during Cycle 1 of a dose level and regarded by the investigators and/or sponsor to be related to the investigational drug.
Time frame: Up to 21 days
Population: MTD evaluation set: All participants of the total dose-escalation group who completed Cycle 1 or discontinued during Cycle 1 due to an adverse event or DLT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rogaratinib Total Dose Escalation | Number of DLTs During Cycle 1 | 0 DLTs |
Secondary
Duration of Response (DOR)
DOR (for partial and complete response (PR/CR)) was defined as the time (days) from the first documented objective response of PR or CR, whichever was noted earlier, to disease progression or death (if death occurred before progression was documented). DOR was calculated for responders only, i.e. participants with complete or partial response. Therefore, the dose escalation group is not displayed.
Time frame: Up to 2 years
Population: Participants with a documented objective response of PR or CR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rogaratinib Total Dose Escalation | Duration of Response (DOR) | 522 Days |
| Rogaratinib Expansion Food Effect | Duration of Response (DOR) | 126 Days |
| Rogaratinib 200 mg BID | Duration of Response (DOR) | 105 Days |
| Rogaratinib 400 mg BID | Duration of Response (DOR) | 225 Days |
Secondary
Duration of Treatment (DOT)
Time frame: Up to 2 years
Population: Participants received at least one dose of Rogaratinib and have post-baseline efficacy data available. Participants were grouped as described in the SAP to allow a comparison of all dose escalation patients (all dose levels pooled together), dose expansion patients (four groups) and total number of patients (overview summaries) in the same table.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rogaratinib Total Dose Escalation | Duration of Treatment (DOT) | 51 Days |
| Rogaratinib Expansion Food Effect | Duration of Treatment (DOT) | 82 Days |
| Rogaratinib 200 mg BID | Duration of Treatment (DOT) | 106 Days |
| Rogaratinib 400 mg BID | Duration of Treatment (DOT) | 49 Days |
| Rogaratinib 600 mg BID | Duration of Treatment (DOT) | 84 Days |
Secondary
Evaluation of Biomarker Status -Change in Serum FGF23 (Fibroblast Growth Factor 23) Levels From Baseline to C2D1
Change in serum FGF23 levels from baseline to C2D1 was reported as ratio to baseline (%).
Time frame: From baseline to C2D1
Population: All participants with FGF23 data available, and participants from expansion groups were combined as pre-specified in the Statistical Analysis Plan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | Evaluation of Biomarker Status -Change in Serum FGF23 (Fibroblast Growth Factor 23) Levels From Baseline to C2D1 | 201.5 Ratio to baseline (%) | Standard Deviation 106.3 |
| Rogaratinib Expansion Food Effect | Evaluation of Biomarker Status -Change in Serum FGF23 (Fibroblast Growth Factor 23) Levels From Baseline to C2D1 | 149.9 Ratio to baseline (%) | — |
| Rogaratinib 200 mg BID | Evaluation of Biomarker Status -Change in Serum FGF23 (Fibroblast Growth Factor 23) Levels From Baseline to C2D1 | 441.9 Ratio to baseline (%) | Standard Deviation 346.2 |
| Rogaratinib 400 mg BID | Evaluation of Biomarker Status -Change in Serum FGF23 (Fibroblast Growth Factor 23) Levels From Baseline to C2D1 | 528.0 Ratio to baseline (%) | Standard Deviation 290.4 |
| Rogaratinib 600 mg BID | Evaluation of Biomarker Status -Change in Serum FGF23 (Fibroblast Growth Factor 23) Levels From Baseline to C2D1 | 402.2 Ratio to baseline (%) | Standard Deviation 35.2 |
| Rogaratinib 800 mg BID | Evaluation of Biomarker Status -Change in Serum FGF23 (Fibroblast Growth Factor 23) Levels From Baseline to C2D1 | 517.7 Ratio to baseline (%) | Standard Deviation 261 |
| Rogaratinib 800 mg BID Pooled | Evaluation of Biomarker Status -Change in Serum FGF23 (Fibroblast Growth Factor 23) Levels From Baseline to C2D1 | 487.0 Ratio to baseline (%) | Standard Deviation 447.7 |
Secondary
Evaluation of Pharmacodynamic Parameters (PD) - Change of Blood Pressure (BP) From Baseline to End of Study
Time frame: From baseline up to 2 years
Population: Participants received at least one dose of Rogaratinib and have valid data for this outcome measure. Participants were grouped as described in the SAP to allow a comparison of all dose escalation patients (all dose levels pooled together), dose expansion patients (four groups) and total number of patients (overview summaries) in the same table.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rogaratinib Total Dose Escalation | Evaluation of Pharmacodynamic Parameters (PD) - Change of Blood Pressure (BP) From Baseline to End of Study | Systolic Blood Pressure | -1.33 mmHg | Standard Deviation 16.44 |
| Rogaratinib Total Dose Escalation | Evaluation of Pharmacodynamic Parameters (PD) - Change of Blood Pressure (BP) From Baseline to End of Study | Diastolic Blood Pressure | -2.50 mmHg | Standard Deviation 13.5 |
| Rogaratinib Expansion Food Effect | Evaluation of Pharmacodynamic Parameters (PD) - Change of Blood Pressure (BP) From Baseline to End of Study | Systolic Blood Pressure | -4.65 mmHg | Standard Deviation 16.73 |
| Rogaratinib Expansion Food Effect | Evaluation of Pharmacodynamic Parameters (PD) - Change of Blood Pressure (BP) From Baseline to End of Study | Diastolic Blood Pressure | -4.76 mmHg | Standard Deviation 6.99 |
| Rogaratinib 200 mg BID | Evaluation of Pharmacodynamic Parameters (PD) - Change of Blood Pressure (BP) From Baseline to End of Study | Systolic Blood Pressure | -2.56 mmHg | Standard Deviation 19.45 |
| Rogaratinib 200 mg BID | Evaluation of Pharmacodynamic Parameters (PD) - Change of Blood Pressure (BP) From Baseline to End of Study | Diastolic Blood Pressure | -0.63 mmHg | Standard Deviation 12.08 |
| Rogaratinib 400 mg BID | Evaluation of Pharmacodynamic Parameters (PD) - Change of Blood Pressure (BP) From Baseline to End of Study | Diastolic Blood Pressure | -0.58 mmHg | Standard Deviation 9.23 |
| Rogaratinib 400 mg BID | Evaluation of Pharmacodynamic Parameters (PD) - Change of Blood Pressure (BP) From Baseline to End of Study | Systolic Blood Pressure | -5.00 mmHg | Standard Deviation 12.37 |
| Rogaratinib 600 mg BID | Evaluation of Pharmacodynamic Parameters (PD) - Change of Blood Pressure (BP) From Baseline to End of Study | Systolic Blood Pressure | -1.83 mmHg | Standard Deviation 18.85 |
| Rogaratinib 600 mg BID | Evaluation of Pharmacodynamic Parameters (PD) - Change of Blood Pressure (BP) From Baseline to End of Study | Diastolic Blood Pressure | 0.41 mmHg | Standard Deviation 12.55 |
Secondary
Evaluation of Pharmacodynamic Parameters (PD) - Change of Heart Rate (HR) From Baseline to End of Study
Time frame: From baseline up to 2 years
Population: Participants received at least one dose of Rogaratinib and have valid data for this outcome measure. Participants were grouped as described in the SAP to allow a comparison of all dose escalation patients (all dose levels pooled together), dose expansion patients (four groups) and total number of patients (overview summaries) in the same table.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | Evaluation of Pharmacodynamic Parameters (PD) - Change of Heart Rate (HR) From Baseline to End of Study | 8.22 beats per minute | Standard Deviation 12.47 |
| Rogaratinib Expansion Food Effect | Evaluation of Pharmacodynamic Parameters (PD) - Change of Heart Rate (HR) From Baseline to End of Study | 6.41 beats per minute | Standard Deviation 15.6 |
| Rogaratinib 200 mg BID | Evaluation of Pharmacodynamic Parameters (PD) - Change of Heart Rate (HR) From Baseline to End of Study | 6.40 beats per minute | Standard Deviation 14.4 |
| Rogaratinib 400 mg BID | Evaluation of Pharmacodynamic Parameters (PD) - Change of Heart Rate (HR) From Baseline to End of Study | 1.42 beats per minute | Standard Deviation 11.65 |
| Rogaratinib 600 mg BID | Evaluation of Pharmacodynamic Parameters (PD) - Change of Heart Rate (HR) From Baseline to End of Study | 6.27 beats per minute | Standard Deviation 15.02 |
Secondary
Evaluation of Pharmacodynamic Parameters (PD) - Change of QT Intervals From Baseline up to Cycle 1, Day 15
Time frame: From baseline up to Cycle 1, Day 15
Population: Safety Analysis Set (SAF): All participants who received at least one dose of the study medication, and valid data for this outcome measure, and participants from dose escalation groups were combined as pre-specified in the Statistical Analysis Plan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | Evaluation of Pharmacodynamic Parameters (PD) - Change of QT Intervals From Baseline up to Cycle 1, Day 15 | 0.60 msec | Standard Deviation 23.11 |
| Rogaratinib Expansion Food Effect | Evaluation of Pharmacodynamic Parameters (PD) - Change of QT Intervals From Baseline up to Cycle 1, Day 15 | 12.86 msec | Standard Deviation 24.16 |
| Rogaratinib 200 mg BID | Evaluation of Pharmacodynamic Parameters (PD) - Change of QT Intervals From Baseline up to Cycle 1, Day 15 | 7.82 msec | Standard Deviation 29.39 |
| Rogaratinib 400 mg BID | Evaluation of Pharmacodynamic Parameters (PD) - Change of QT Intervals From Baseline up to Cycle 1, Day 15 | 2.89 msec | Standard Deviation 16.47 |
| Rogaratinib 600 mg BID | Evaluation of Pharmacodynamic Parameters (PD) - Change of QT Intervals From Baseline up to Cycle 1, Day 15 | 6.41 msec | Standard Deviation 21.14 |
Secondary
Evaluation of Relative Bioavailability of the Tablet Formulation in Comparison to the Solution Formulation of BAY1163877
In order to evaluate the relative bioavailability of the tablet formulation, tablet Cmax/D, AUC(0-tlast)/D, and AUC/D on Cycle 1, Day -3 were compared to solution Cmax/D, AUC(0-tlast)/D, AUC/D on Cycle 1, Day 1 for all analytes. The logarithms of the PK parameters were analyzed using analysis of variance (ANOVA) including participant and formulation effects. Based on these analyses, point estimates (LS-means) and exploratory 90% confidence intervals for the ratios (tablet/solution) of Cmax/D, AUC(0- tlast)/D, and AUC/D were calculated by re-transformation of the logarithmic data using the intra-individual standard deviation of the ANOVA.
Time frame: On Cycle 1, Day -3 and Cycle 1, Day 1
Population: Only participants who received both tablet and solution formulation were included in the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | Evaluation of Relative Bioavailability of the Tablet Formulation in Comparison to the Solution Formulation of BAY1163877 | AUC/D | 0.9776 ratio |
| Rogaratinib Total Dose Escalation | Evaluation of Relative Bioavailability of the Tablet Formulation in Comparison to the Solution Formulation of BAY1163877 | AUC(0-tlast)/D | 0.9945 ratio |
| Rogaratinib Total Dose Escalation | Evaluation of Relative Bioavailability of the Tablet Formulation in Comparison to the Solution Formulation of BAY1163877 | Cmax/D | 0.6335 ratio |
Secondary
Progression-free Survival (PFS)
PFS was defined as the time (days) from the date of the first dose of study drug to the date of the first observed disease progression (radiological or clinical) or death due to any cause, if death occurred before progression was documented. PFS for participants without tumor progression at the time of analysis was censored at their last date of tumor evaluation.
Time frame: Up to 2 years
Population: Participants received at least one dose of Rogaratinib and have post-baseline efficacy data available. Participants were grouped as described in the SAP to allow a comparison of all dose escalation patients (all dose levels pooled together), dose expansion patients (four groups) and total number of patients (overview summaries) in the same table.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rogaratinib Total Dose Escalation | Progression-free Survival (PFS) | 45 Days |
| Rogaratinib Expansion Food Effect | Progression-free Survival (PFS) | 47 Days |
| Rogaratinib 200 mg BID | Progression-free Survival (PFS) | 105 Days |
| Rogaratinib 400 mg BID | Progression-free Survival (PFS) | 44 Days |
| Rogaratinib 600 mg BID | Progression-free Survival (PFS) | 84 Days |
Secondary
Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type
Response as defined by RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1: complete response (CR: disappearance of all target lesions), partial response (PR: at least a 30% decrease in the sum of diameters of target lesions taking as the reference the baseline sum of diameters), stable disease (SD: steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as a reference, the smallest sum of diameters while in the trial), progressive disease (PD: at least a 20% increase in the sum of diameters of the target lesions, taking as a references the smallest sum on study).
Time frame: Up to 2 years
Population: Participants received at least one dose of Rogaratinib and have post-baseline efficacy data available. Participants were grouped as described in the SAP to allow a comparison of all dose escalation patients (all dose levels pooled together), dose expansion patients (four groups) and total number of patients (overview summaries) in the same table.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | PR | 0 Participants |
| Rogaratinib Total Dose Escalation | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | missing | 2 Participants |
| Rogaratinib Total Dose Escalation | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | CR | 0 Participants |
| Rogaratinib Total Dose Escalation | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | PD | 9 Participants |
| Rogaratinib Total Dose Escalation | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | SD | 10 Participants |
| Rogaratinib Expansion Food Effect | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | PD | 8 Participants |
| Rogaratinib Expansion Food Effect | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | CR | 0 Participants |
| Rogaratinib Expansion Food Effect | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | SD | 12 Participants |
| Rogaratinib Expansion Food Effect | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | missing | 1 Participants |
| Rogaratinib Expansion Food Effect | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | PR | 1 Participants |
| Rogaratinib 200 mg BID | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | missing | 1 Participants |
| Rogaratinib 200 mg BID | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | PD | 20 Participants |
| Rogaratinib 200 mg BID | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | SD | 34 Participants |
| Rogaratinib 200 mg BID | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | CR | 1 Participants |
| Rogaratinib 200 mg BID | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | PR | 14 Participants |
| Rogaratinib 400 mg BID | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | CR | 0 Participants |
| Rogaratinib 400 mg BID | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | missing | 1 Participants |
| Rogaratinib 400 mg BID | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | PD | 3 Participants |
| Rogaratinib 400 mg BID | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | PR | 1 Participants |
| Rogaratinib 400 mg BID | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | SD | 2 Participants |
| Rogaratinib 600 mg BID | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | PD | 11 Participants |
| Rogaratinib 600 mg BID | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | CR | 0 Participants |
| Rogaratinib 600 mg BID | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | missing | 2 Participants |
| Rogaratinib 600 mg BID | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | SD | 22 Participants |
| Rogaratinib 600 mg BID | Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type | PR | 2 Participants |
Secondary
T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1
T1/2 (half-life associated with the terminal slope) of BAY1163877 after single dose administration on Cycle 1, Day -3 and Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hour(s) post-dose
Population: All participants with valid PK data on Cycle 1, Day -3 and on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Rogaratinib Total Dose Escalation | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 8.34 hours | Geometric Coefficient of Variation 24.9 |
| Rogaratinib Total Dose Escalation | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours | — |
| Rogaratinib Expansion Food Effect | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | 8.15 hours | Geometric Coefficient of Variation 22.3 |
| Rogaratinib Expansion Food Effect | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 8.93 hours | Geometric Coefficient of Variation 40.2 |
| Rogaratinib 200 mg BID | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours | — |
| Rogaratinib 200 mg BID | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 7.51 hours | Geometric Coefficient of Variation 19.2 |
| Rogaratinib 400 mg BID | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours | — |
| Rogaratinib 400 mg BID | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 7.93 hours | Geometric Coefficient of Variation 54.2 |
| Rogaratinib 600 mg BID | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 8.51 hours | Geometric Coefficient of Variation 29.4 |
| Rogaratinib 600 mg BID | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours | — |
| Rogaratinib 800 mg BID | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours | — |
| Rogaratinib 800 mg BID | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 9.29 hours | Geometric Coefficient of Variation 9.86 |
| Rogaratinib 800 mg BID Pooled | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 11.7 hours | Geometric Coefficient of Variation 44.3 |
| Rogaratinib 800 mg BID Pooled | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours | — |
| Rogaratinib Expansion Food Effect | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 12.5 hours | Geometric Coefficient of Variation 38.7 |
| Rogaratinib Expansion Food Effect | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | 8.22 hours | Geometric Coefficient of Variation 31.6 |
| Rogaratinib Dose Expansion (All Comers) | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 12.3 hours | Geometric Coefficient of Variation 52.1 |
| Rogaratinib Dose Expansion (All Comers) | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours | — |
| Rogaratinib Dose Expansion (BC) | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 11.5 hours | Geometric Coefficient of Variation 42.7 |
| Rogaratinib Dose Expansion (BC) | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours | — |
| Rogaratinib Dose Expansion (SCCHN) | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 14.1 hours | Geometric Coefficient of Variation 57.7 |
| Rogaratinib Dose Expansion (SCCHN) | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours | — |
| Rogaratinib Dose Expansion (sqNSCLC) | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours | — |
| Rogaratinib Dose Expansion (sqNSCLC) | T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 11.4 hours | Geometric Coefficient of Variation 41 |
Secondary
Time to Progression (TTP)
TTP was defined as the time from start of study treatment until first observed disease progression (radiological or clinical). Progression is defined using RECIST v1.0, as at least a 20% increase in the sum of diameters of the target lesions, taking as a references the smallest sum on study.
Time frame: Up to 2 years
Population: Participants received at least one dose of Rogaratinib and have post-baseline efficacy data available. Participants were grouped as described in the SAP to allow a comparison of all dose escalation patients (all dose levels pooled together), dose expansion patients (four groups) and total number of patients (overview summaries) in the same table.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rogaratinib Total Dose Escalation | Time to Progression (TTP) | 45 Days |
| Rogaratinib Expansion Food Effect | Time to Progression (TTP) | 47 Days |
| Rogaratinib 200 mg BID | Time to Progression (TTP) | 105 Days |
| Rogaratinib 400 mg BID | Time to Progression (TTP) | 68 Days |
| Rogaratinib 600 mg BID | Time to Progression (TTP) | 85 Days |
Secondary
Tlast,md (Time of Last Plasma Concentration Above LLOQ After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
Tlast,md (time of last plasma concentration above LLOQ after multiple-dose administration) of BAY1163877. Median and full range were reported.
Time frame: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Population: All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rogaratinib Total Dose Escalation | Tlast,md (Time of Last Plasma Concentration Above LLOQ After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 9.80 hours |
| Rogaratinib Expansion Food Effect | Tlast,md (Time of Last Plasma Concentration Above LLOQ After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 11.7 hours |
| Rogaratinib 200 mg BID | Tlast,md (Time of Last Plasma Concentration Above LLOQ After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 11.6 hours |
| Rogaratinib 400 mg BID | Tlast,md (Time of Last Plasma Concentration Above LLOQ After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 11.7 hours |
| Rogaratinib 600 mg BID | Tlast,md (Time of Last Plasma Concentration Above LLOQ After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 11.6 hours |
| Rogaratinib 800 mg BID | Tlast,md (Time of Last Plasma Concentration Above LLOQ After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 11.7 hours |
| Rogaratinib 800 mg BID Pooled | Tlast,md (Time of Last Plasma Concentration Above LLOQ After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 11.7 hours |
| Rogaratinib Expansion Food Effect | Tlast,md (Time of Last Plasma Concentration Above LLOQ After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 11.7 hours |
| Rogaratinib Dose Expansion (All Comers) | Tlast,md (Time of Last Plasma Concentration Above LLOQ After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 11.5 hours |
| Rogaratinib Dose Expansion (BC) | Tlast,md (Time of Last Plasma Concentration Above LLOQ After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 12.0 hours |
| Rogaratinib Dose Expansion (SCCHN) | Tlast,md (Time of Last Plasma Concentration Above LLOQ After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 11.4 hours |
| Rogaratinib Dose Expansion (sqNSCLC) | Tlast,md (Time of Last Plasma Concentration Above LLOQ After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 11.7 hours |
Secondary
Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1
Tlast (time of last plasma concentration above LLOQ) of BAY1163877 after single dose administration on Cycle 1, Day -3 and Cycle 1, Day 1. Median and full range were reported.
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hour(s) post-dose
Population: All participants with valid PK data on Cycle 1, Day -3 and on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours |
| Rogaratinib Total Dose Escalation | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 47.7 hours |
| Rogaratinib Expansion Food Effect | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | 48.1 hours |
| Rogaratinib Expansion Food Effect | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 47.9 hours |
| Rogaratinib 200 mg BID | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours |
| Rogaratinib 200 mg BID | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 47.9 hours |
| Rogaratinib 400 mg BID | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours |
| Rogaratinib 400 mg BID | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 46.9 hours |
| Rogaratinib 600 mg BID | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 48.0 hours |
| Rogaratinib 600 mg BID | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours |
| Rogaratinib 800 mg BID | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours |
| Rogaratinib 800 mg BID | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 47.9 hours |
| Rogaratinib 800 mg BID Pooled | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 47.9 hours |
| Rogaratinib 800 mg BID Pooled | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours |
| Rogaratinib Expansion Food Effect | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | 48.0 hours |
| Rogaratinib Expansion Food Effect | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 47.6 hours |
| Rogaratinib Dose Expansion (All Comers) | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours |
| Rogaratinib Dose Expansion (All Comers) | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 47.9 hours |
| Rogaratinib Dose Expansion (BC) | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours |
| Rogaratinib Dose Expansion (BC) | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 48.0 hours |
| Rogaratinib Dose Expansion (SCCHN) | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 48.2 hours |
| Rogaratinib Dose Expansion (SCCHN) | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours |
| Rogaratinib Dose Expansion (sqNSCLC) | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 47.8 hours |
| Rogaratinib Dose Expansion (sqNSCLC) | Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours |
Secondary
Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
Tmax,md (time to reach maximum drug concentration in plasma after multiple-dose administration) of BAY1163877. Median and full range were reported.
Time frame: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Population: All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rogaratinib Total Dose Escalation | Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 0.80 hours |
| Rogaratinib Expansion Food Effect | Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 1.08 hours |
| Rogaratinib 200 mg BID | Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 1.12 hours |
| Rogaratinib 400 mg BID | Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 2.08 hours |
| Rogaratinib 600 mg BID | Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 2.10 hours |
| Rogaratinib 800 mg BID | Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 2.56 hours |
| Rogaratinib 800 mg BID Pooled | Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 2.00 hours |
| Rogaratinib Expansion Food Effect | Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 3.17 hours |
| Rogaratinib Dose Expansion (All Comers) | Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 1.98 hours |
| Rogaratinib Dose Expansion (BC) | Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 1.98 hours |
| Rogaratinib Dose Expansion (SCCHN) | Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 2.07 hours |
| Rogaratinib Dose Expansion (sqNSCLC) | Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15 | 2.00 hours |
Secondary
Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1
Tmax (time to reach maximum drug concentration in plasma) of BAY1163877 after single dose administration on Cycle 1, Day -3 and Cycle 1, Day 1. Median and full range were reported.
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hour(s) post-dose
Population: All participants with valid PK data on Cycle 1, Day -3 and on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours |
| Rogaratinib Total Dose Escalation | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 0.633 hours |
| Rogaratinib Expansion Food Effect | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | 2.02 hours |
| Rogaratinib Expansion Food Effect | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 0.783 hours |
| Rogaratinib 200 mg BID | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours |
| Rogaratinib 200 mg BID | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 1.02 hours |
| Rogaratinib 400 mg BID | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours |
| Rogaratinib 400 mg BID | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 1.02 hours |
| Rogaratinib 600 mg BID | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 1.54 hours |
| Rogaratinib 600 mg BID | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours |
| Rogaratinib 800 mg BID | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours |
| Rogaratinib 800 mg BID | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 2.53 hours |
| Rogaratinib 800 mg BID Pooled | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 2.00 hours |
| Rogaratinib 800 mg BID Pooled | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours |
| Rogaratinib Expansion Food Effect | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | 2.99 hours |
| Rogaratinib Expansion Food Effect | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 2.00 hours |
| Rogaratinib Dose Expansion (All Comers) | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours |
| Rogaratinib Dose Expansion (All Comers) | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 2.00 hours |
| Rogaratinib Dose Expansion (BC) | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours |
| Rogaratinib Dose Expansion (BC) | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 1.00 hours |
| Rogaratinib Dose Expansion (SCCHN) | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 1.28 hours |
| Rogaratinib Dose Expansion (SCCHN) | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours |
| Rogaratinib Dose Expansion (sqNSCLC) | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day 1 | 2.02 hours |
| Rogaratinib Dose Expansion (sqNSCLC) | Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1 | Cycle 1, Day -3 | NA hours |