Dose Escalation Pan-FGFR (Fibroblast Growth Factor Recept... | NCT01976741

ID	Type	Description	Link
2013-002155-15	EudraCT Number

Label	Type	Description	Intervention Names
Rogaratinib total dose escalation	Experimental	Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.	Drug: Rogaratinib (BAY1163877) oral solution Drug: Rogaratinib (BAY1163877) oral tablet
Rogaratinib dose expansion (All Comers)	Experimental	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 b.i.d. (1600 mg/day) in 21-days cycles.	Drug: Rogaratinib (BAY1163877) 800 mg BID
Rogaratinib dose expansion (BC)	Experimental	Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet b.i.d. (1600 mg/day) in 21-days cycles.	Drug: Rogaratinib (BAY1163877) 800 mg BID
Rogaratinib dose expansion (SCCHN)	Experimental	Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet b.i.d. (1600 mg/day) in 21-days cycles.

Name	Type	Description	Arm Group Labels	Other Names
Rogaratinib (BAY1163877) oral solution	Drug	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.

Measure	Description	Time Frame
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.	Up to 21 days
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.	Up to 21 days
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.	pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
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.	pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
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.

Measure	Description	Time Frame
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).

Name	Affiliation	Role
Bayer Study Director	Bayer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Chicago	Illinois	60611-2908	United States

PubMed Identifier	Type	Citation	Retractions
31405822	Result	Schuler M, Cho BC, Sayehli CM, Navarro A, Soo RA, Richly H, Cassier PA, Tai D, Penel N, Nogova L, Park SH, Schostak M, Gajate P, Cathomas R, Rajagopalan P, Grevel J, Bender S, Boix O, Nogai H, Ocker M, Ellinghaus P, Joerger M. Rogaratinib in patients with advanced cancers selected by FGFR mRNA expression: a phase 1 dose-escalation and dose-expansion study. Lancet Oncol. 2019 Oct;20(10):1454-1466. doi: 10.1016/S1470-2045(19)30412-7. Epub 2019 Aug 9.
30807645

ID	Title	Description
FG000	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.
FG001	Rogaratinib 100 mg BID

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 17, 2018	Feb 26, 2020

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum Tolerated Dose (MTD), 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.

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.

Posted

Number

mg BID

Up to 21 days

ID	Title	Description
OG000	Rogaratinib Total Dose Escalation	Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.

Units	Counts
Participants	OG00021

Title

Denominators

Categories

Title	Measurements
	OG000800

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.

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.

Posted

Number

DLTs

Up to 21 days

ID	Title	Description
OG000	Rogaratinib Total Dose Escalation	Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.

Units	Counts
Participants	OG000

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.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

µg/L

pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)

ID	Title	Description
OG000	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.
OG001	Rogaratinib Expansion Food Effect	For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.

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.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

µg/L

pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)

ID	Title	Description
OG000	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.
OG001	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.
OG002	Rogaratinib 200 mg BID

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.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

µg*h/L

pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)

ID	Title	Description
OG000	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.
OG001	Rogaratinib Expansion Food Effect	For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

µg*h/L

pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)

ID	Title	Description
OG000	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.
OG001	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.

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.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

µg*h/L

pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)

ID	Title	Description
OG000	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.
OG001	Rogaratinib Expansion Food Effect	For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.

Primary

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

µg*h/L

pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)

ID	Title	Description
OG000	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.
OG001	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.

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.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

µg*h/L

pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)

ID	Title	Description
OG000	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.
OG001	Rogaratinib Expansion Food Effect	For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

µg*h/L

pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)

ID	Title	Description
OG000	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.
OG001	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.
OG002

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.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)

ID	Title	Description
OG000	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.
OG001	Rogaratinib Expansion Food Effect	For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)

ID	Title	Description
OG000	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.
OG001	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.
OG002

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.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h/L

pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)

ID	Title	Description
OG000	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.
OG001	Rogaratinib Expansion Food Effect	For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h/L

pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)

ID	Title	Description
OG000	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.
OG001	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.

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.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h/L

pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)

ID	Title	Description
OG000	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.
OG001	Rogaratinib Expansion Food Effect	For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h/L

pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)

ID	Title	Description
OG000	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.
OG001	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.

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.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h/L

pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)

ID	Title	Description
OG000	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.
OG001	Rogaratinib Expansion Food Effect	For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h/L

pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)

ID	Title	Description
OG000	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.
OG001	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.
OG002	Rogaratinib 200 mg BID

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.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

µg/L

pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose

ID	Title	Description
OG000	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.
OG001	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.
OG002	Rogaratinib 200 mg BID

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose

ID	Title	Description
OG000	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.
OG001	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.
OG002	Rogaratinib 200 mg BID

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

µg*h/L

pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose

ID	Title	Description
OG000	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.
OG001	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.
OG002	Rogaratinib 200 mg BID

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h/L

pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose

ID	Title	Description
OG000	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.
OG001	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.
OG002	Rogaratinib 200 mg BID

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

µg*h/L

pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose

ID	Title	Description
OG000	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.
OG001	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.
OG002	Rogaratinib 200 mg BID

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h/L

pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose

ID	Title	Description
OG000	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.
OG001	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.
OG002	Rogaratinib 200 mg BID

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.

Urine interval samples on C1D1 were collected in a subgroup of subjects from the 800 mg BID expansion part.

Posted

Median

Full Range

percentage

On Cycle1, Day 1

ID	Title	Description
OG000	Rogaratinib 800 mg BID Pooled	Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.

Units	Counts
Participants	OG000

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.

Urine interval samples on C1D1 were collected in a subgroup of subjects from the 800 mg BID expansion part.

Posted

Median

Full Range

percentage

On Cycle1, Day 1

ID	Title	Description
OG000	Rogaratinib 800 mg BID Pooled	Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.

Units	Counts
Participants	OG000

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.

Urine interval samples on C1D1 were collected in a subgroup of subjects from the 800 mg BID expansion part.

Posted

Median

Full Range

percentage

On Cycle1, Day 1

ID	Title	Description
OG000	Rogaratinib 800 mg BID Pooled	Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.

Units	Counts
Participants	OG000

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).

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.

Posted

Count of Participants

Participants

Up to 2 years

ID	Title	Description
OG000	Rogaratinib Total Dose Escalation	Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.

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.

Posted

Median

95% Confidence Interval

Days

Up to 2 years

ID	Title	Description
OG000	Rogaratinib Total Dose Escalation	Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
OG001	Rogaratinib Dose Expansion (All Comers)

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.

Posted

Median

95% Confidence Interval

Days

Up to 2 years

ID	Title	Description
OG000	Rogaratinib Total Dose Escalation	Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
OG001	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.

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.

Participants with a documented objective response of PR or CR.

Posted

Median

95% Confidence Interval

Days

Up to 2 years

ID	Title	Description
OG000	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.
OG001	Rogaratinib Dose Expansion (BC)	Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
OG002	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.

Secondary

Duration of Treatment (DOT)

Posted

Median

95% Confidence Interval

Days

Up to 2 years

ID	Title	Description
OG000	Rogaratinib Total Dose Escalation	Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
OG001	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.
OG002

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 (%).

All participants with FGF23 data available, and participants from expansion groups were combined as pre-specified in the Statistical Analysis Plan.

Posted

Mean

Standard Deviation

Ratio to baseline (%)

From baseline to C2D1

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Evaluation of Pharmacodynamic Parameters (PD) - Change of Heart Rate (HR) From Baseline to End of Study

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.

Posted

Mean

Standard Deviation

beats per minute

From baseline up to 2 years

ID	Title	Description
OG000	Rogaratinib Total Dose Escalation	Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
OG001	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.

Secondary

Evaluation of Pharmacodynamic Parameters (PD) - Change of Blood Pressure (BP) From Baseline to End of Study

Posted

Mean

Standard Deviation

mmHg

From baseline up to 2 years

ID	Title	Description
OG000	Rogaratinib Total Dose Escalation	Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
OG001	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.

Secondary

Evaluation of Pharmacodynamic Parameters (PD) - Change of QT Intervals From Baseline up to Cycle 1, Day 15

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.

Posted

Mean

Standard Deviation

msec

From baseline up to Cycle 1, Day 15

ID	Title	Description
OG000	Rogaratinib Total Dose Escalation	Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
OG001	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.
OG002

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.

Only participants who received both tablet and solution formulation were included in the analysis.

Posted

Geometric Least Squares Mean

90% Confidence Interval

ratio

On Cycle 1, Day -3 and Cycle 1, Day 1

ID	Title	Description
OG000	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.

Units	Counts
Participants

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.

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.

Posted

Median

Full Range

hours

pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hour(s) post-dose

ID	Title	Description
OG000	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.
OG001	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.
OG002	Rogaratinib 200 mg BID

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.

Posted

Median

Full Range

hours

pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hour(s) post-dose

ID	Title	Description
OG000	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.
OG001	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.
OG002	Rogaratinib 200 mg BID

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

hours

pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hour(s) post-dose

ID	Title	Description
OG000	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.
OG001	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.
OG002

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.

Posted

Median

Full Range

hours

pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose

ID	Title	Description
OG000	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.
OG001	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.
OG002	Rogaratinib 200 mg BID

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.

Posted

Median

Full Range

hours

pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose

ID	Title	Description
OG000	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.
OG001	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.
OG002	Rogaratinib 200 mg BID

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Splenic infarction	Blood and lymphatic system disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG0030 events0 affected8 at risk EG004
Tracheo-oesophageal fistula	Congenital, familial and genetic disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Retinopathy	Eye disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected23 at risk EG0021 events1 affected74 at risk EG003
Chronic gastritis	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Ileus	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0002 events1 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Subileus	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Death	General disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Fatigue	General disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected23 at risk EG0011 events1 affected23 at risk EG0023 events2 affected74 at risk EG003
Pain	General disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Pyrexia	General disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected23 at risk EG0022 events2 affected74 at risk EG003
Sudden death	General disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
General physical health deterioration	General disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0027 events5 affected74 at risk EG003
Multiple organ dysfunction syndrome	General disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0012 events2 affected23 at risk EG0022 events2 affected74 at risk EG003
Hepatic function abnormal	Hepatobiliary disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected23 at risk EG0020 events0 affected74 at risk EG003
Bronchitis	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Cellulitis	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Gastrointestinal infection	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Herpes zoster	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Infection	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Kidney infection	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Oesophageal candidiasis	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Pneumonia	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected23 at risk EG0012 events1 affected23 at risk EG0023 events2 affected74 at risk EG003
Sepsis	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected23 at risk EG0020 events0 affected74 at risk EG003
Septic shock	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0022 events2 affected74 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0028 events5 affected74 at risk EG003
Urosepsis	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0023 events3 affected74 at risk EG003
Arthritis bacterial	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Escherichia bacteraemia	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected23 at risk EG0020 events0 affected74 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0022 events1 affected74 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Tracheal obstruction	Injury, poisoning and procedural complications	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Amylase increased	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected23 at risk EG0020 events0 affected74 at risk EG003
Blood bilirubin increased	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Blood creatinine increased	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Lipase increased	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0022 events1 affected74 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA (22.1)	Non-systematic Assessment	EG0005 events1 affected23 at risk EG0014 events2 affected23 at risk EG0021 events1 affected74 at risk EG003
Hyperphosphataemia	Metabolism and nutrition disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected23 at risk EG0020 events0 affected74 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0022 events2 affected74 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0013 events1 affected23 at risk EG0020 events0 affected74 at risk EG003
Neck mass	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Metastases to lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Pharyngeal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0024 events3 affected74 at risk EG003
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected23 at risk EG0020 events0 affected74 at risk EG003
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0022 events1 affected74 at risk EG003
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected23 at risk EG0020 events0 affected74 at risk EG003
Presyncope	Nervous system disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Seizure	Nervous system disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Somnolence	Nervous system disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Spinal cord oedema	Nervous system disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Dural arteriovenous fistula	Nervous system disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Azotaemia	Renal and urinary disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Hydronephrosis	Renal and urinary disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0022 events2 affected74 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Renal pain	Renal and urinary disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Urinary tract obstruction	Renal and urinary disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Bladder tamponade	Renal and urinary disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0022 events2 affected74 at risk EG003
Perineal pain	Reproductive system and breast disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0004 events3 affected23 at risk EG0011 events1 affected23 at risk EG0021 events1 affected74 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected23 at risk EG0020 events0 affected74 at risk EG003
Laryngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Tracheal stenosis	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Nephrostomy	Surgical and medical procedures	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Hypotension	Vascular disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Peripheral vascular disorder	Vascular disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Arterial haemorrhage	Vascular disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Peripheral arterial occlusive disease	Vascular disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (22.1)	Non-systematic Assessment	EG0002 events2 affected23 at risk EG00111 events4 affected23 at risk EG00229 events17 affected74 at risk EG0036 events3 affected8 at risk EG00419 events12 affected40 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0014 events2 affected23 at risk EG0020 events0 affected74 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0015 events2 affected23 at risk EG0020 events0 affected74 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected23 at risk EG0011 events1 affected23 at risk EG0020 events0 affected74 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Dry eye	Eye disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0013 events2 affected23 at risk EG00213 events12 affected74 at risk EG003
Glaucoma	Eye disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0024 events4 affected74 at risk EG003
Retinal detachment	Eye disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected23 at risk EG0023 events2 affected74 at risk EG003
Retinopathy	Eye disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Growth of eyelashes	Eye disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0023 events3 affected74 at risk EG003
Detachment of retinal pigment epithelium	Eye disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0022 events2 affected74 at risk EG003
Pingueculitis	Eye disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0012 events2 affected23 at risk EG0022 events2 affected74 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0012 events2 affected23 at risk EG00214 events11 affected74 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0024 events4 affected74 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0002 events1 affected23 at risk EG0010 events0 affected23 at risk EG0022 events1 affected74 at risk EG003
Breath odour	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0003 events2 affected23 at risk EG00116 events10 affected23 at risk EG00241 events25 affected74 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0008 events4 affected23 at risk EG00120 events13 affected23 at risk EG002106 events48 affected74 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0012 events2 affected23 at risk EG00242 events25 affected74 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected23 at risk EG0013 events2 affected23 at risk EG0025 events5 affected74 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0012 events2 affected23 at risk EG0023 events3 affected74 at risk EG003
Enterocolitis	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0026 events4 affected74 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0008 events7 affected23 at risk EG00111 events8 affected23 at risk EG00231 events20 affected74 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0002 events2 affected23 at risk EG0013 events2 affected23 at risk EG00218 events11 affected74 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0004 events2 affected23 at risk EG0011 events1 affected23 at risk EG00218 events13 affected74 at risk EG003
Asthenia	General disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0018 events3 affected23 at risk EG00235 events14 affected74 at risk EG003
Chest pain	General disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected23 at risk EG0015 events4 affected23 at risk EG0021 events1 affected74 at risk EG003
Fatigue	General disorders	MedDRA (22.1)	Non-systematic Assessment	EG0008 events7 affected23 at risk EG00112 events7 affected23 at risk EG00255 events28 affected74 at risk EG003
Mucosal inflammation	General disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0014 events1 affected23 at risk EG0027 events4 affected74 at risk EG003
Oedema	General disorders	MedDRA (22.1)	Non-systematic Assessment	EG0003 events3 affected23 at risk EG0011 events1 affected23 at risk EG0023 events2 affected74 at risk EG003
Oedema peripheral	General disorders	MedDRA (22.1)	Non-systematic Assessment	EG0002 events2 affected23 at risk EG0015 events2 affected23 at risk EG0025 events4 affected74 at risk EG003
Pyrexia	General disorders	MedDRA (22.1)	Non-systematic Assessment	EG0003 events2 affected23 at risk EG0018 events6 affected23 at risk EG00211 events7 affected74 at risk EG003
Bronchitis	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected23 at risk EG0011 events1 affected23 at risk EG0020 events0 affected74 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0023 events3 affected74 at risk EG003
Infection	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected23 at risk EG0024 events4 affected74 at risk EG003
Paronychia	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0015 events3 affected23 at risk EG0029 events6 affected74 at risk EG003
Pneumonia	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0002 events2 affected23 at risk EG0013 events2 affected23 at risk EG0021 events1 affected74 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0012 events1 affected23 at risk EG0024 events4 affected74 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0014 events3 affected23 at risk EG00232 events19 affected74 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0012 events1 affected23 at risk EG0024 events4 affected74 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0022 events2 affected74 at risk EG003
Tooth injury	Injury, poisoning and procedural complications	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0002 events1 affected23 at risk EG0015 events4 affected23 at risk EG00220 events8 affected74 at risk EG003
Amylase increased	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0014 events2 affected23 at risk EG00220 events6 affected74 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0002 events2 affected23 at risk EG0016 events5 affected23 at risk EG00219 events9 affected74 at risk EG003
Blood bilirubin increased	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0015 events3 affected23 at risk EG0029 events7 affected74 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected23 at risk EG0027 events4 affected74 at risk EG003
Blood creatinine increased	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0014 events3 affected23 at risk EG00224 events12 affected74 at risk EG003
Blood lactate dehydrogenase increased	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0013 events2 affected23 at risk EG0020 events0 affected74 at risk EG003
C-reactive protein increased	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0024 events4 affected74 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected23 at risk EG00216 events7 affected74 at risk EG003
Lipase increased	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected23 at risk EG00113 events3 affected23 at risk EG00240 events10 affected74 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0002 events1 affected23 at risk EG0010 events0 affected23 at risk EG0022 events1 affected74 at risk EG003
Neutrophil count decreased	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected23 at risk EG0011 events1 affected23 at risk EG0027 events5 affected74 at risk EG003
Platelet count decreased	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Weight decreased	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0029 events5 affected74 at risk EG003
Blood phosphorus increased	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG00021 events11 affected23 at risk EG00158 events20 affected23 at risk EG00288 events31 affected74 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected23 at risk EG00212 events7 affected74 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA (22.1)	Non-systematic Assessment	EG0002 events1 affected23 at risk EG00113 events5 affected23 at risk EG00210 events7 affected74 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected23 at risk EG0024 events2 affected74 at risk EG003
Hyperphosphataemia	Metabolism and nutrition disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0014 events2 affected23 at risk EG00211 events6 affected74 at risk EG003
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA (22.1)	Non-systematic Assessment	EG0002 events2 affected23 at risk EG0010 events0 affected23 at risk EG00225 events4 affected74 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0012 events2 affected23 at risk EG0026 events3 affected74 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (22.1)	Non-systematic Assessment	EG0003 events3 affected23 at risk EG0012 events2 affected23 at risk EG00210 events6 affected74 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0012 events2 affected23 at risk EG0021 events1 affected74 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0013 events2 affected23 at risk EG0026 events5 affected74 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected23 at risk EG0025 events4 affected74 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (22.1)	Non-systematic Assessment	EG0009 events5 affected23 at risk EG00112 events10 affected23 at risk EG00250 events29 affected74 at risk EG003
Hyperlipasaemia	Metabolism and nutrition disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0012 events2 affected23 at risk EG0021 events1 affected74 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0004 events2 affected23 at risk EG0019 events5 affected23 at risk EG00230 events17 affected74 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0002 events2 affected23 at risk EG0014 events4 affected23 at risk EG00217 events12 affected74 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected23 at risk EG0028 events8 affected74 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected23 at risk EG0022 events2 affected74 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0012 events2 affected23 at risk EG0025 events3 affected74 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0014 events3 affected23 at risk EG0029 events6 affected74 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected23 at risk EG0020 events0 affected74 at risk EG003
Chest wall haematoma	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Skin cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected23 at risk EG0027 events5 affected74 at risk EG003
Dizziness	Nervous system disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected23 at risk EG0013 events3 affected23 at risk EG0025 events4 affected74 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected23 at risk EG0013 events3 affected23 at risk EG00220 events17 affected74 at risk EG003
Headache	Nervous system disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected23 at risk EG0012 events2 affected23 at risk EG0023 events2 affected74 at risk EG003
Lethargy	Nervous system disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0014 events2 affected23 at risk EG0020 events0 affected74 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0012 events2 affected23 at risk EG0025 events5 affected74 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected23 at risk EG0016 events2 affected23 at risk EG0021 events1 affected74 at risk EG003
Syncope	Nervous system disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Taste disorder	Nervous system disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0025 events5 affected74 at risk EG003
Depression	Psychiatric disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (22.1)	Non-systematic Assessment	EG0002 events2 affected23 at risk EG0015 events5 affected23 at risk EG0023 events3 affected74 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected23 at risk EG0025 events4 affected74 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG00213 events9 affected74 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Chronic kidney disease	Renal and urinary disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0004 events2 affected23 at risk EG0014 events4 affected23 at risk EG0028 events7 affected74 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0012 events2 affected23 at risk EG0023 events3 affected74 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0004 events3 affected23 at risk EG0010 events0 affected23 at risk EG0029 events6 affected74 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected23 at risk EG0025 events5 affected74 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected23 at risk EG00210 events5 affected74 at risk EG003
Laryngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Nasal dryness	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0003 events3 affected23 at risk EG0010 events0 affected23 at risk EG0021 events1 affected74 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0003 events2 affected23 at risk EG0011 events1 affected23 at risk EG0021 events1 affected74 at risk EG003
Throat irritation	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0013 events3 affected23 at risk EG0025 events5 affected74 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0002 events1 affected23 at risk EG0016 events6 affected23 at risk EG00223 events20 affected74 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0012 events2 affected23 at risk EG00222 events17 affected74 at risk EG003
Hypertrichosis	Skin and subcutaneous tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Nail discolouration	Skin and subcutaneous tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0012 events2 affected23 at risk EG0028 events7 affected74 at risk EG003
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected23 at risk EG00213 events7 affected74 at risk EG003
Nail dystrophy	Skin and subcutaneous tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0017 events2 affected23 at risk EG0021 events1 affected74 at risk EG003
Nail hypertrophy	Skin and subcutaneous tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Onycholysis	Skin and subcutaneous tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0014 events1 affected23 at risk EG00222 events12 affected74 at risk EG003
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0014 events2 affected23 at risk EG00216 events7 affected74 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0002 events2 affected23 at risk EG0010 events0 affected23 at risk EG0025 events5 affected74 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0025 events4 affected74 at risk EG003
Onychomadesis	Skin and subcutaneous tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0012 events1 affected23 at risk EG0024 events4 affected74 at risk EG003
Haemorrhoid operation	Surgical and medical procedures	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003
Hypertension	Vascular disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0026 events4 affected74 at risk EG003
Hypotension	Vascular disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected23 at risk EG0012 events1 affected23 at risk EG0022 events1 affected74 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected23 at risk EG0020 events0 affected74 at risk EG003

ID	Title	Description
BG000	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.
BG001	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.
BG002	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.
BG003	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.
BG004	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.
BG005	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.
BG006	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.
BG007	Rogaratinib Dose Expansion (BC)	Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
BG008	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.
BG009	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.
BG010	Total	Total of all reporting groups

ID	Term
D009369	Neoplasms
D009362	Neoplasm Metastasis
D001749	Urinary Bladder Neoplasms
D000077192	Adenocarcinoma of Lung
D006258	Head and Neck Neoplasms

ID	Term
D009385	Neoplastic Processes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D014571	Urologic Neoplasms
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D001745	Urinary Bladder Diseases
D014570	Urologic Diseases
D052801	Male Urogenital Diseases
D000230	Adenocarcinoma
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms

ID	Term
C000630155	Rogaratinib
D012996	Solutions
D013607	Tablets
C494814	BID protein, human

ID	Term
D004364	Pharmaceutical Preparations
D004304	Dosage Forms

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Rogaratinib Total Dose Escalation	Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.	3	23	9	23	22	23
EG001	Rogaratinib Dose Expansion (All Comers)	Subjects 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.	6	23	14	23	23	23
EG002	Rogaratinib Dose Expansion (BC)	Subjects with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.	17	74	44	74	73	74
EG003	Rogaratinib Dose Expansion (SCCHN)	Subjects with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.	2	8	5	8	8	8
EG004	Rogaratinib Dose Expansion (sqNSCLC)	Subjects with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.	12	40	24	40	40	40