FORT-1: Study of Rogaratinib (BAY1163877) vs Chemotherapy in Patients With FGFR (Fibroblast Growth Factor Receptor)-Positive Locally Advanced or Metastatic Urothelial Carcinoma

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03410693
• Collaborator: (none)
• Enrollment: 175
• Locations: 161
• Arms: 2
• Actual Duration (Months): 28.9
• Patients Per Site: 1.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is a randomized, open-label, multicenter Phase 2/3 study to evaluate the efficacy and safety of rogaratinib (BAY 1163877) compared to chemotherapy in patients with FGFR-positive locally advanced or metastatic urothelial carcinoma who have received prior platinum-containing chemotherapy.

The primary objective is to demonstrate the superiority of rogaratinib over chemotherapy in terms of objective response rate (before: overall survivial) of urothelial carcinoma patients with FGFR positive tumors.

At randomization, patients will have locally advanced or metastatic urothelial carcinoma and have received at least one prior platinum-containing chemotherapy regimen. Only patients with FGFR1 or 3 positive tumors can be randomized into the study. Archival tumor tissue is adequate for testing of FGFR1 and 3 mRNA expressions, which will be determined centrally using an RNA in situ hybridization (RNA-ISH) test. Approximately 42 % of UC patients with locally advanced or metastatic UC are identified as FGFR-positive by the RNA-ISH cut-off applied.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Transitional Cell	Drug: Rogaratinib (BAY1163877); Drug: Chemotherapy	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 175 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open Label, Multicenter Phase 2/3 Study to Evaluate the Efficacy and Safety of Rogaratinib (BAY1163877) Compared to Chemotherapy in Patients With FGFR-positive Locally Advanced or Metastatic Urothelial Carcinoma Who Have Received Prior Platinum-containing Chemotherapy
• Actual Study Start Date: May 31, 2018
• Actual Primary Completion Date: Oct 27, 2020
• Actual Study Completion Date: Oct 27, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rogaratinib Rogaratinib treatment study arm, comprising Pre-treatment period, including FGFR testing and screening, Treatment period, and Follow-up period, including active follow-up and long-term follow-up. Patients will be considered "on study" during the pre-treatment, treatment and active followup periods. During the long-term follow-up period the patients will be considered "off study".	Drug: Rogaratinib (BAY1163877); Rogaratinib administered as oral (p.o.) tablets twice daily (b.i.d.) continuously
Active Comparator: Chemotherapy Chemotherapy treatment study arm, comprising Pre-treatment period, including FGFR testing and screening, Treatment period, and Follow-up period, including active follow-up and long-term follow-up. Patients will be considered "on study" during the pre-treatment, treatment and active followup periods. During the long-term follow-up period the patients will be considered "off study".	Drug: Chemotherapy; Chemotherapy as taxane (docetaxel or paclitaxel) or vinflunine administered through intravenous (i.v.) infusion every 3 weeks (on day 1 of a 21-day cycle) The choice of the chemotherapy is at the discretion of the investigator, taking into consideration the status of the authorization or treatment guidelines in the given country.

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) - Central Assessment [From start of treatment up to end of active follow-up, approximately 29 months]

   ORR is defined as the percentage of participants with complete response (CR) or partial response (PR). participants for whom overall best response is not CR or PR, as well as participants without any post-baseline tumor assessment will be considered non-responders.

Secondary Outcome Measures

1. Disease-control Rate (DCR) - Central Assessment [From start of treatment till end of active follow-up, approximately 29 months]

   DCR was defined as the percentage of participants whose overall best response was not a progressive disease (i.e., CR, PR, stable disease [SD] or Non CR/Non PD).

2. Progression-free Survival (PFS) - Central Assessment [From start of treatment till end of active follow-up, approximately 29 months]

   Progression free survival (PFS) was defined as the time (days) from randomization to date of first observed disease progression (radiological or clinical assessment or both) or death due to any cause (if death occurred before progression was documented).

3. Duration of Response (DOR) - Central Assessment [From start of treatment till end of active follow-up, approximately 29 months]

   DOR (for patients with PR and CR only) was defined as the time from the first documented objective response of PR or CR, whichever was noted earlier, to disease progression (including symptomatic deterioration) or death, whichever was earlier

4. Number of Participants With Treatment Emergent Adverse Events [From start of treatment up to 30 days after the last administration of study treatment, approximately 29 months]

   A treatment-emergent event was defined as any event arising or worsening after the start of study drug administration until 30 days after the last administration of study treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Existence of archival or fresh biopsy for FGFR testing. Mandatory FGFR testing of patients will be performed prior to start of screening. The timing of the FGFR test is at the discretion of the investigator. Investigators should ensure all patients will be eligible in terms of disease status and lines of treatment.

• Documented urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra meeting all of the following criteria

• Histologically confirmed (Patients with mixed histologies are required to have a dominant transitional cell pattern.)

• Locally advanced (T4, any N; or any T, N 2-3) or metastatic disease (any T, any N and M1). Locally advanced bladder cancer must be unresectable i.e. invading the pelvic or abdominal wall (stage T4b) or presenting with bulky nodal disease (N2-3).

• ECOG (Eastern Cooperative Oncology Group) Performance Status of 0 or 1

• Disease progression during or following treatment with at least one platinum-containing regimen (patients should have been treated for at least 2 cycles). In patients who received prior adjuvant/ neoadjuvant platinum-containing chemotherapy, progression had to occur within 12 months of treatment.

• High FGFR1 or 3 mRNA expression levels in archival or fresh tumor biopsy specimen quantified as outlined in the lab manual

• At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST v.1.1) in contrast enhanced (unless contraindicated) CT or MRI

Exclusion Criteria:

• Previous or concurrent cancer except

• cervical carcinoma in situ

• treated basal-cell or squamous cell skin carcinoma

• any cancer curatively treated > 3 years before randomization

• curatively treated incidental prostate cancer (T1/T2a)

• Ongoing or previous treatment with anti-FGFR directed therapies (e.g. receptor tyrosine kinase inhibitors including rogaratinib or FGFR-specific antibodies) or with taxanes or vinflunine

• More than two prior lines of systemic anti-cancer therapy for urothelial carcinoma given for advanced unresectable/ metastatic disease

• Ongoing or previous anti-cancer treatment within 4 weeks before randomization.

• Unresolved toxicity higher than National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE v.4.03) Grade 1 attributed to any prior therapy/ procedure excluding alopecia, anemia and/ or hypothyroidism

• History or current condition of an uncontrolled cardiovascular disease including any of the following conditions:

• Congestive heart failure (CHF) NYHA (New York Heart Association) > Class 2

• Unstable angina (symptoms of angina at rest) or new-onset angina (within last 3 months before randomization)

• Myocardial infarction (MI) within past 6 months before randomization

• Unstable cardiac arrhythmias requiring anti-arrhythmic therapy. Patients with arrhythmia under control with anti-arrhythmic therapy such as beta-blockers or digoxin are eligible.

• Arterial or venous thrombotic events or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before randomization

• Current evidence of endocrine alteration of calcium phosphate homeostasis (e.g. parathyroid disorder, history of parathyroidectomy, tumor lysis, tumoral calcinosis, paraneoplastic hypercalcemia)

• Current diagnosis of any retinal detachment, retinal pigment epithelial detachment (RPED), serous retinopathy or retinal vein occlusion

• Any hemorrhage / bleeding event ≥ CTCAE v.4.03 Grade 3 within 4 weeks before randomization

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alaska Clinical Research Center, LLC	Anchorage	Alaska	United States	99503
2	University of Arizona Cancer Center	Tucson	Arizona	United States	85719
3	University of Southern California	Los Angeles	California	United States	90033
4	UC Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
5	Sansum Clinic	Santa Barbara	California	United States	93105
6	Rocky Mountain Cancer Centers	Littleton	Colorado	United States	80120-4413
7	UF Cancer Center at Orlando Health	Orlando	Florida	United States	32806
8	University of Kansas Medical Center	Westwood	Kansas	United States	66205
9	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89169
10	Compass Oncology	Tigard	Oregon	United States	97223
11	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15232
12	Bon Secours St. Francis Hospital	Greenville	South Carolina	United States	29607
13	Texas Oncology-Denton South	Denton	Texas	United States	76210
14	Houston Methodist Hospital	Houston	Texas	United States	77030-2707
15	Virginia Mason Medical Center	Seattle	Washington	United States	98101
16	Summit Cancer Center	Spokane	Washington	United States	99208
17	Mid North Coast Cancer Institute	Coffs Harbour	New South Wales	Australia	2450
18	Northern Cancer Institute	St Leonards	New South Wales	Australia	2065
19	Macquarie University Hospital	Sydney	New South Wales	Australia	2109
20	Riverina Cancer Care Centre	Wagga Wagga	New South Wales	Australia	2650
21	Sydney Adventist Hospital	Wahroonga	New South Wales	Australia	2076
22	Pindara Private Hospital	Benowa	Queensland	Australia	4217
23	Monash Medical Centre	Clayton	Victoria	Australia	3168
24	Landesklinikum Krems	Krems		Austria	3500
25	Krankenhaus der Barmherzigen Brüder	Wien		Austria	1020
26	Universitätsklinikum AKH Wien	Wien		Austria	1090
27	Klinik Ottakring - Wilhelminenspital	Wien		Austria	1160
28	UZ Gent	Gent		Belgium	9000
29	UZ Leuven Gasthuisberg	Leuven		Belgium	3000
30	Clinique Saint-Pierre	Ottignies		Belgium	1340
31	Princess Margaret Hospital-University Health Network	Toronto	Ontario	Canada	M5G 2M9
32	Sir Mortimer B. Davis Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
33	Ottawa Hospital-General Campus	Ottawa		Canada	K1H 8L6
34	FuJian Medical University Union Hospital	Fuzhou	Fujian	China	350001
35	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong	China	510060
36	Hubei Cancer Hospital	Wuhan	Hubei	China	430079
37	NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School	Nanjing	Jiangsu	China	210008
38	Jiangsu Cancer Hospital	Nanjing	Jiangsu	China	210009
39	Liaoning Cancer Hospital and Institute	Shengyang	Liaoning	China	110042
40	Fifth Medical Center, General Hospital of the Chinese People	Beijing		China	100071
41	First Affiliated Hospital of Guangzhou Medical University	Guangzhou		China
42	Fudan University Shanghai Cancer Center	Shanghai		China	200032
43	Huadong Hospital, Affiliated to Fudan University	Shanghai		China	200040
44	Fakultni nemocnice Ostrava	Ostrava		Czechia	708 52
45	Fakultni nemocnice Kralovske Vinohrady	Praha 10		Czechia	10034
46	Fakultni Thomayerova Nemocnice	Praha 4 - Krc		Czechia	140 59
47	Bata Hospital	Zlin		Czechia	762 75
48	Aarhus Universitetshospital, Skejby	Aarhus N		Denmark	8200
49	Herlev Hospital	Herlev		Denmark	2730
50	Rigshospitalet	København		Denmark	2100
51	Docrates Klinikka	Helsinki		Finland	00180
52	Hopital Jean Minjoz	Besancon		France	25030
53	Hôpital Saint André - Bordeaux	Bordeaux		France	33000
54	Centre de Lutte Contre le Cancer François Baclesse	Caen Cedex 5		France	14076
55	Centre Jean Perrin	Clermont Ferrand Cedex 1		France	63011
56	Centre Oscar Lambret - Lille	Lille Cedex		France	59020
57	Centre Léon Bérard	Lyon Cedex		France	69008
58	Institut Paoli-Calmettes - Marseille	Marseille		France	13273
59	Cochin - Paris	Paris		France	75674
60	Hôpital d'Instruction des Armées Begin	Saint Mande		France	94160
61	Clinique Saint Anne	Strasbourg		France	67000
62	Centre Médico-Chirurgical Foch	Suresnes		France	92151
63	Eberhard-Karls-Universität Tübingen	Tübingen	Baden-Württemberg	Germany	72076
64	Heinrich-Heine-Universität Düsseldorf	Düsseldorf	Nordrhein-Westfalen	Germany	40225
65	Universitätsmedizin der Johannes Gutenberg Universität Mainz	Mainz	Rheinland-Pfalz	Germany	55131
66	Prince of Wales Hospital	Shatin		Hong Kong
67	MH Egeszsegugyi Kozpont	Budapest		Hungary	1062
68	Orszagos Onkologiai Intezet	Budapest		Hungary	1122
69	Pecsi Tudomanyegyetem Klinikai Kozpont	Pecs		Hungary	7624
70	Cork University Hospital	Cork		Ireland
71	AMNCH	Dublin		Ireland	24
72	Rambam Health Corporation	Haifa		Israel	3109601
73	Hadassah Hebrew University Hospital Ein Kerem	Jerusalem		Israel	9112001
74	Meir Medical Center	Kfar Saba		Israel	4428164
75	Clalit Health Services Rabin Medical Center-Beilinson Campus	Petah Tikva		Israel	4941492
76	Chaim Sheba Medical Center	Ramat Gan		Israel	5266202
77	IRST Istituto Scientifico Romagnolo per studio e cura tumori	Forlì Cesena	Emilia-Romagna	Italy	47014
78	AUSL Modena	Modena	Emilia-Romagna	Italy	41012
79	A.O.U. di Modena - Policlinico	Modena	Emilia-Romagna	Italy	41124
80	A.O. San Camillo-Forlanini	Roma	Lazio	Italy	00152
81	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma	Lazio	Italy	00168
82	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano	Lombardia	Italy	20133
83	IRCCS Istituto Europeo di Oncologia s.r.l. (IEO)	Milano	Lombardia	Italy	20141
84	ASST Grande Ospedale Metropolitano Niguarda	Milano	Lombardia	Italy	20162
85	A.O.U. San Luigi Gonzaga	Torino	Piemonte	Italy	10043
86	A.O.U. Pisana	Pisa	Toscana	Italy	56126
87	A.O.U.I. Verona	Verona	Veneto	Italy	37134
88	Nagoya University Hospital	Nagoya	Aichi	Japan	466-8560
89	Hirosaki University Hospital	Hirosaki	Aomori	Japan	036-8563
90	Gunma University Hospital	Maebashi	Gunma	Japan	371-8511
91	Gunma Prefectural Cancer Center	Ota	Gunma	Japan	373-8550
92	Sapporo Medical University Hospital	Sapporo	Hokkaido	Japan	060-8543
93	Hokkaido University Hospital	Sapporo	Hokkaido	Japan	060-8648
94	Kobe City Medical Center General Hospital	Kobe	Hyogo	Japan	650-0047
95	University of Tsukuba Hospital	Tsukuba	Ibaraki	Japan	305-8576
96	Iwate Medical University Hospital	Morioka	Iwate	Japan	028-3695
97	Yokohama City University Hospital	Yokohama	Kanagawa	Japan	236-0004
98	Kindai University Hospital	Osakasayama	Osaka	Japan	589-8511
99	Saitama Medical University International Medical Center	Hidaka	Saitama	Japan	350-1298
100	Nippon Medical School Hospital	Bunkyo-ku	Tokyo	Japan	113-8603
101	National Cancer Center Hospital	Chuo-ku	Tokyo	Japan	104-0045
102	The Cancer Institute Hospital of JFCR	Koto-ku	Tokyo	Japan	135-8550
103	Keio University Hospital	Shinjuku-ku	Tokyo	Japan	160-8582
104	Akita University Hospital	Akita		Japan	010-8543
105	Kyushu University Hospital	Fukuoka		Japan	812-8582
106	Hiroshima City Hiroshima Citizens Hospital	Hiroshima		Japan	730-8518
107	Kumamoto University Hospital	Kumamoto		Japan	860-8556
108	Niigata University Medical and Dental Hospital	Niigata		Japan	951-8520
109	Osaka International Cancer Institute	Osaka		Japan	541-8567
110	Toyama University Hospital	Toyama		Japan	930-0194
111	National Cancer Center	Goyang-si	Gyeonggido	Korea, Republic of	10408
112	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
113	Asan Medical Center	Seoul		Korea, Republic of	05505
114	Samsung Medical Center	Seoul		Korea, Republic of	06351
115	Nederlands Kanker Instituut	Amsterdam		Netherlands	1066 CX
116	Erasmus Medisch Centrum	Rotterdam		Netherlands	3075 EA
117	Centrum Onkologii im. Prof. Franciszka Lukaszczyka	Bydgoszcz		Poland	85-796
118	Swietokrzyskie Centrum Onkologii	Kielce		Poland	25-734
119	Przychodnia Lekarska KOMED	Konin		Poland	62-500
120	Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc	Olsztyn		Poland	10-357
121	Szpital Kliniczny Przemienienia Panskiego	Poznan		Poland	60-569
122	Uniwersytecki Szpital Kliniczny UM we Wroclawiu	Wroclaw		Poland	50-556
123	Hospital Beatriz Angelo	Loures	Lisboa	Portugal	2674-514
124	IPO Coimbra	Coimbra		Portugal	3000-075
125	Hospital CUF Infante Santo	Lisboa		Portugal	1350-070
126	CHULN - Hospital Santa Maria	Lisboa		Portugal	1649-035
127	CHUP - Hospital Santo Antonio	Porto		Portugal	4099-001
128	Krasnoyarsk Regional Clinical Oncology Dispensary	Krasnoyarsk		Russian Federation	660133
129	Moscow Scient. Res. Institute of Oncology n.a P.A. Hertzen	Moscow		Russian Federation	125284
130	Volga District Med Center FMBA	Nizhny Novgorod		Russian Federation	603109
131	Clinical Oncological Dispensary of Omsk Region	Omsk		Russian Federation	644013
132	Bashkir State Medical University	Ufa		Russian Federation	450008
133	National University Hospital	Singapore		Singapore	119074
134	National Cancer Center Singapore	Singapore		Singapore	169610
135	Narodny onkologicky ustav	Bratislava		Slovakia	833 10
136	UROEXAM, spol. s r.o.	Nitra		Slovakia	949 01
137	POKO Poprad s.r.o.	Poprad		Slovakia	085 01
138	Institut Català d'Oncologia Badalona	Badalona	Barcelona	Spain	08916
139	Institut Català d'Oncologia Hospitalet	L'Hospitalet de Llobregat	Barcelona	Spain	08907
140	Hospital Universitari Son Espases	Palma de Mallorca	Illes Baleares	Spain	07120
141	Hospital del Mar	Barcelona		Spain	08003
142	Ciutat Sanitària i Universitaria de la Vall d'Hebron	Barcelona		Spain	08035
143	Hospital San Pedro de Alcántara	Cáceres		Spain	10003
144	Hospital Reina Sofía	Córdoba		Spain	14004
145	Hospital Ramón y Cajal	Madrid		Spain	28034
146	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
147	Hospital Virgen de la Victoria	Málaga		Spain	29010
148	Instituto Valenciano de Oncología	Valencia		Spain	46009
149	Hospital General Universitario de Valencia	Valencia		Spain	46014
150	Södersjukhuset	Stockholm		Sweden	118 83
151	Karolinska Institutet	Stockholm		Sweden	17167
152	Universitätsspital Basel	Basel	Basel-Stadt	Switzerland	4031
153	Kantonsspital Graubünden	Chur	Graubünden	Switzerland	7000
154	Kantonsspital St. Gallen	St. Gallen	Sankt Gallen	Switzerland	9007
155	Taichung Veterans General Hospital	Taichung		Taiwan	40705
156	National Cheng Kung University Hospital	Tainan		Taiwan	704
157	National Taiwan University Hospital	Taipei		Taiwan	10002
158	Taipei Veterans General Hospital	Taipei		Taiwan	11217
159	Chang Gung Memorial Hospital at Linkou	Taoyuan		Taiwan	33305
160	Clatterbridge Centre for Oncology	Bebington	Merseyside	United Kingdom	CH63 4JY
161	Royal Marsden Hospital (London)	London		United Kingdom	SW3 6JJ

Sponsors and Collaborators

• Bayer

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

• Study Protocol - Nov 19, 2019
• Statistical Analysis Plan - Aug 19, 2020

More Information

Additional Information:

• Click here to find results for studies related to Bayer Healthcare products.
• Click here to find information about studies related to Bayer Healthcare products conducted in Europe.

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT03410693
• Other Study ID Numbers: 17403; 2016-004340-11
• First Posted: Jan 25, 2018
• Last Update Posted: Feb 14, 2022
• Last Verified: Feb 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Bayer: Urothelial carcinoma
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Transitional Cell

Study Results

Participant Flow

Recruitment Details	This study enrolled participants at 111centers in 28 countries from 31 MAY 2018 (first participant first visit) to 27 OCT 2020 (last participant last visit).
Pre-assignment Detail	A total of 718 participants signed the informed consent for prescreening, of which 256 participants completed the prescreening, while 462 participants discontinued the prescreening. The discontinuations were due to screening failure (322), other reasons (98), withdrawal by the participant (22), and death (20).

Arm/Group Title	Rogaratinib (BAY1163877)_Overall Population	Chemotherapy_Overall Population
Arm/Group Description	Participants who were randomized to this group following a 1:1 ratio received rogaratinib 600 mg orally twice a day (b.i.d.) continuously, during a 21-day treatment cycle.	Participants who were randomized to this group following a 1:1 ratio received chemotherapy (docetaxel, paclitaxel or vinflunine) at the discretion of the investigator, as intravenous (i.v.) infusion once every three weeks (on day 1 of a 21-day cycle).
Period Title: Overall Study
STARTED	87	88
Started Treatment	86	82
Active Follow-up Performed	61	56
Entered Long Term Follow-up	56	69
COMPLETED	0	0
NOT COMPLETED	87	88

Baseline Characteristics

Arm/Group Title	Rogaratinib (BAY1163877)_Overall Population	Chemotherapy_Overall Population	Total
Arm/Group Description	Participants who were randomized to this group following a 1:1 ratio received rogaratinib 600 mg orally twice a day (b.i.d.) continuously, during a 21-day treatment cycle.	Participants who were randomized to this group following a 1:1 ratio received chemotherapy (docetaxel, paclitaxel or vinflunine) at the discretion of the investigator, as intravenous (i.v.) infusion once every three weeks (on day 1 of a 21-day cycle).	Total of all reporting groups
Overall Participants	87	88	175
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.7 (8.3)	66.4 (10.3)	67.0 (9.3)
Sex: Female, Male (Count of Participants)
Female	75 86.2%	70 79.5%	145 82.9%
Male	12 13.8%	18 20.5%	30 17.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 1.1%	0 0%	1 0.6%
Not Hispanic or Latino	76 87.4%	78 88.6%	154 88%
Unknown or Not Reported	10 11.5%	10 11.4%	20 11.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	23 26.4%	25 28.4%	48 27.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 1.1%	0 0%	1 0.6%
White	55 63.2%	55 62.5%	110 62.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	8 9.2%	8 9.1%	16 9.1%
Cancer Category (Count of Participants)
Location of primary cancer: bladder	56 64.4%	45 51.1%	101 57.7%
Location of primary cancer: Ureter	17 19.5%	14 15.9%	31 17.7%
Location of primary cancer: Renal pelvis	12 13.8%	28 31.8%	40 22.9%
Location of primary cancer: Proximal urethra	2 2.3%	1 1.1%	3 1.7%
Cancer stage at study entry (Count of Participants)
Stage III B	1 1.1%	3 3.4%	4 2.3%
Stage IV	5 5.7%	12 13.6%	17 9.7%
Stage IV A	13 14.9%	24 27.3%	37 21.1%
Stage IV B	67 77%	48 54.5%	115 65.7%
Unknown	1 1.1%	1 1.1%	2 1.1%
PIK3CA and/or RAS activating mutations (Count of Participants)
Absent	65 74.7%	69 78.4%	134 76.6%
Present	10 11.5%	10 11.4%	20 11.4%
Unknown	12 13.8%	9 10.2%	21 12%
FGFR expression from Targos (Count of Participants)
Negative	13 14.9%	14 15.9%	27 15.4%
Positive	69 79.3%	69 78.4%	138 78.9%
Not assessed	5 5.7%	5 5.7%	10 5.7%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR) - Central Assessment
Description	ORR is defined as the percentage of participants with complete response (CR) or partial response (PR). participants for whom overall best response is not CR or PR, as well as participants without any post-baseline tumor assessment will be considered non-responders.
Time Frame	From start of treatment up to end of active follow-up, approximately 29 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rogaratinib (BAY1163877)_Overall Population	Chemotherapy_Overall Population	Rogaratinib_WT Population	Chemotherapy_WT Population
Arm/Group Description	Participants who were randomized to this group following a 1:1 ratio received rogaratinib 600 mg orally twice a day (b.i.d.) continuously, during a 21-day treatment cycle.	Participants who were randomized to this group following a 1:1 ratio received chemotherapy (docetaxel, paclitaxel or vinflunine) at the discretion of the investigator, as intravenous (i.v.) infusion once every three weeks (on day 1 of a 21-day cycle).	Rogaratinib arm, wild type population	Chemotherapy group, wild type population
Measure Participants	87	88	62	63
Number (95% Confidence Interval) [percentage of participants]	19.5 22.4%	21.6 24.5%	19.4 11.1%	23.8 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rogaratinib (BAY1163877)_Overall Population, Chemotherapy_Overall Population
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.6991
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	ORR difference (R-C)
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 95%; -14.0 to 9.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Rogaratinib_WT Population, Chemotherapy_WT Population
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.7944
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	ORR difference (R - C)
	Estimated Value	-4.5
	Confidence Interval	(2-Sided) 95%; -18.9 to 9.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Disease-control Rate (DCR) - Central Assessment
Description	DCR was defined as the percentage of participants whose overall best response was not a progressive disease (i.e., CR, PR, stable disease [SD] or Non CR/Non PD).
Time Frame	From start of treatment till end of active follow-up, approximately 29 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rogaratinib (BAY1163877)_Overall Population	Chemotherapy_Overall Population	Rogaratinib_WT Population	Chemotherapy_WT Population
Arm/Group Description	Participants who were randomized to this group following a 1:1 ratio received rogaratinib 600 mg orally twice a day (b.i.d.) continuously, during a 21-day treatment cycle.	Participants who were randomized to this group following a 1:1 ratio received chemotherapy (docetaxel, paclitaxel or vinflunine) at the discretion of the investigator, as intravenous (i.v.) infusion once every three weeks (on day 1 of a 21-day cycle).	Rogaratinib arm, Wild type population	Chemotherapy group, Wild type population
Measure Participants	87	88	62	63
Number (95% Confidence Interval) [percentage of participants]	50.6 58.2%	55.7 63.3%	53.2 30.4%	63.5 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rogaratinib (BAY1163877)_Overall Population, Chemotherapy_Overall Population
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.7962
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	DCR difference (R-C)
	Estimated Value	-5.1
	Confidence Interval	(2-Sided) 95%; -19.9 to 9.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Rogaratinib_WT Population, Chemotherapy_WT Population
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.9109
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	DCR difference (R-C)
	Estimated Value	-10.3
	Confidence Interval	(2-Sided) 95%; -27.5 to 6.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Progression-free Survival (PFS) - Central Assessment
Description	Progression free survival (PFS) was defined as the time (days) from randomization to date of first observed disease progression (radiological or clinical assessment or both) or death due to any cause (if death occurred before progression was documented).
Time Frame	From start of treatment till end of active follow-up, approximately 29 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rogaratinib (BAY1163877)_Overall Population	Chemotherapy_Overall Population	Rogaratinib_WT Population	Chemotherapy_WT Population
Arm/Group Description	Participants who were randomized to this group following a 1:1 ratio received rogaratinib 600 mg orally twice a day (b.i.d.) continuously, during a 21-day treatment cycle.	Participants who were randomized to this group following a 1:1 ratio received chemotherapy (docetaxel, paclitaxel or vinflunine) at the discretion of the investigator, as intravenous (i.v.) infusion once every three weeks (on day 1 of a 21-day cycle).	Rogaratinib arm, Wild type population	Chemotherapy group, Wild type population
Measure Participants	87	88	62	63
Median (95% Confidence Interval) [months]	2.7	3.2	2.8	4.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rogaratinib (BAY1163877)_Overall Population, Chemotherapy_Overall Population
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	= 0.8672
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.226
	Confidence Interval	(2-Sided) 95%; 0.853 to 1.762
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Rogaratinib_WT Population, Chemotherapy_WT Population
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9171
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.341
	Confidence Interval	(2-Sided) 95%; 0.880 to 2.043
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Duration of Response (DOR) - Central Assessment
Description	DOR (for patients with PR and CR only) was defined as the time from the first documented objective response of PR or CR, whichever was noted earlier, to disease progression (including symptomatic deterioration) or death, whichever was earlier
Time Frame	From start of treatment till end of active follow-up, approximately 29 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rogaratinib (BAY1163877)_Overall Population	Chemotherapy_Overall Population	Rogaratinib_WT Population	Chemotherapy_WT Population
Arm/Group Description	Participants who were randomized to this group following a 1:1 ratio received rogaratinib 600 mg orally twice a day (b.i.d.) continuously, during a 21-day treatment cycle.	Participants who were randomized to this group following a 1:1 ratio received chemotherapy (docetaxel, paclitaxel or vinflunine) at the discretion of the investigator, as intravenous (i.v.) infusion once every three weeks (on day 1 of a 21-day cycle).	Rogaratinib arm, Wild type population	Chemotherapy group, Wild type population
Measure Participants	87	88	62	63
Median (95% Confidence Interval) [months]	4.9	5.8	5.1	7.0

5. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events
Description	A treatment-emergent event was defined as any event arising or worsening after the start of study drug administration until 30 days after the last administration of study treatment
Time Frame	From start of treatment up to 30 days after the last administration of study treatment, approximately 29 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rogaratinib (BAY1163877)	Chemotherapy
Arm/Group Description	Participants who were randomized to this group following a 1:1 ratio received rogaratinib 600 mg orally twice a day (b.i.d.) continuously, during a 21-day treatment cycle.	Participants who were randomized to this group following a 1:1 ratio received chemotherapy (docetaxel, paclitaxel or vinflunine) at the discretion of the investigator, as intravenous (i.v.) infusion once every three weeks (on day 1 of a 21-day cycle).
Measure Participants	86	82
Any TEAE	86 98.9%	82 93.2%
Any drug related TEAE	81 93.1%	76 86.4%

Adverse Events

Time Frame	Approximately 29 months
Adverse Event Reporting Description	A treatment-emergent adverse event reported in this study was defined as any event arising or worsening after the start of study drug administration until 30 days after the last administration of study treatment.
Arm/Group Title	Rogaratinib (BAY1163877)		Chemotherapy
Arm/Group Description	Participants who were randomized to this group following a 1:1 ratio received rogaratinib 600 mg orally twice a day (b.i.d.) continuously, during a 21-day treatment cycle.		Participants who were randomized to this group following a 1:1 ratio received chemotherapy (docetaxel, paclitaxel or vinflunine) at the discretion of the investigator, as intravenous (i.v.) infusion once every three weeks (on day 1 of a 21-day cycle).
All Cause Mortality
	Rogaratinib (BAY1163877)		Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	47/86 (54.7%)		45/82 (54.9%)
Serious Adverse Events
	Rogaratinib (BAY1163877)		Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/86 (45.3%)		33/82 (40.2%)
Blood and lymphatic system disorders
Anaemia	0/86 (0%)	0	1/82 (1.2%)	1
Febrile neutropenia	0/86 (0%)	0	4/82 (4.9%)	4
Neutropenia	0/86 (0%)	0	4/82 (4.9%)	6
Thrombocytopenia	1/86 (1.2%)	1	0/82 (0%)	0
Cardiac disorders
Acute myocardial infarction	1/86 (1.2%)	1	0/82 (0%)	0
Cardiopulmonary failure	1/86 (1.2%)	1	0/82 (0%)	0
Gastrointestinal disorders
Abdominal pain	3/86 (3.5%)	3	0/82 (0%)	0
Colitis ischaemic	1/86 (1.2%)	1	0/82 (0%)	0
Diarrhoea	0/86 (0%)	0	2/82 (2.4%)	2
Inguinal hernia	1/86 (1.2%)	1	0/82 (0%)	0
Intestinal obstruction	1/86 (1.2%)	1	0/82 (0%)	0
Intussusception	1/86 (1.2%)	1	0/82 (0%)	0
Nausea	1/86 (1.2%)	1	0/82 (0%)	0
Pancreatitis	1/86 (1.2%)	1	0/82 (0%)	0
Small intestinal obstruction	1/86 (1.2%)	1	0/82 (0%)	0
Volvulus	1/86 (1.2%)	1	0/82 (0%)	0
Vomiting	1/86 (1.2%)	1	1/82 (1.2%)	1
General disorders
Asthenia	1/86 (1.2%)	1	0/82 (0%)	0
Condition aggravated	2/86 (2.3%)	2	0/82 (0%)	0
Death	4/86 (4.7%)	4	2/82 (2.4%)	2
Mucosal inflammation	1/86 (1.2%)	1	0/82 (0%)	0
Oedema peripheral	0/86 (0%)	0	1/82 (1.2%)	1
Pain	1/86 (1.2%)	1	0/82 (0%)	0
Pyrexia	1/86 (1.2%)	1	1/82 (1.2%)	1
General physical health deterioration	4/86 (4.7%)	6	1/82 (1.2%)	1
Multiple organ dysfunction syndrome	1/86 (1.2%)	1	0/82 (0%)	0
Hepatobiliary disorders
Cholecystitis	1/86 (1.2%)	1	0/82 (0%)	0
Cholelithiasis	1/86 (1.2%)	1	0/82 (0%)	0
Hepatic failure	1/86 (1.2%)	1	0/82 (0%)	0
Infections and infestations
Bronchitis	0/86 (0%)	0	1/82 (1.2%)	1
Cellulitis	1/86 (1.2%)	1	2/82 (2.4%)	2
Pneumonia	0/86 (0%)	0	2/82 (2.4%)	2
Relapsing fever	1/86 (1.2%)	1	0/82 (0%)	0
Sepsis	0/86 (0%)	0	3/82 (3.7%)	3
Urinary tract infection	1/86 (1.2%)	1	4/82 (4.9%)	4
Wound infection	1/86 (1.2%)	1	0/82 (0%)	0
Urosepsis	1/86 (1.2%)	1	2/82 (2.4%)	2
Groin infection	0/86 (0%)	0	1/82 (1.2%)	1
Klebsiella infection	0/86 (0%)	0	1/82 (1.2%)	1
Respiratory tract infection	0/86 (0%)	0	1/82 (1.2%)	2
Device related infection	1/86 (1.2%)	1	0/82 (0%)	0
Pneumocystis jirovecii pneumonia	0/86 (0%)	0	1/82 (1.2%)	1
Escherichia pyelonephritis	0/86 (0%)	0	1/82 (1.2%)	1
Injury, poisoning and procedural complications
Fall	1/86 (1.2%)	1	1/82 (1.2%)	1
Femoral neck fracture	0/86 (0%)	0	1/82 (1.2%)	1
Hip fracture	1/86 (1.2%)	2	0/82 (0%)	0
Periprosthetic fracture	1/86 (1.2%)	1	0/82 (0%)	0
Investigations
Aspartate aminotransferase increased	1/86 (1.2%)	1	0/82 (0%)	0
Biopsy liver	1/86 (1.2%)	1	0/82 (0%)	0
Blood creatinine increased	2/86 (2.3%)	7	0/82 (0%)	0
Lipase increased	1/86 (1.2%)	1	0/82 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/86 (1.2%)	1	0/82 (0%)	0
Hypercalcaemia	1/86 (1.2%)	2	0/82 (0%)	0
Hypomagnesaemia	0/86 (0%)	0	1/82 (1.2%)	1
Decreased appetite	0/86 (0%)	0	1/82 (1.2%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/86 (1.2%)	1	0/82 (0%)	0
Musculoskeletal pain	1/86 (1.2%)	2	0/82 (0%)	0
Osteonecrosis	1/86 (1.2%)	1	0/82 (0%)	0
Pain in extremity	0/86 (0%)	0	1/82 (1.2%)	1
Nervous system disorders
Epilepsy	0/86 (0%)	0	1/82 (1.2%)	1
Hepatic encephalopathy	1/86 (1.2%)	1	0/82 (0%)	0
Neurotoxicity	0/86 (0%)	0	1/82 (1.2%)	2
Peripheral sensory neuropathy	0/86 (0%)	0	1/82 (1.2%)	1
Renal and urinary disorders
Anuria	0/86 (0%)	0	1/82 (1.2%)	1
Haematuria	1/86 (1.2%)	1	3/82 (3.7%)	4
Hydronephrosis	0/86 (0%)	0	1/82 (1.2%)	1
Nephritis	1/86 (1.2%)	1	0/82 (0%)	0
Oliguria	0/86 (0%)	0	1/82 (1.2%)	1
Haemorrhage urinary tract	0/86 (0%)	0	1/82 (1.2%)	1
Postrenal failure	1/86 (1.2%)	1	0/82 (0%)	0
Urinary tract obstruction	1/86 (1.2%)	1	1/82 (1.2%)	1
Acute kidney injury	3/86 (3.5%)	4	2/82 (2.4%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnoea	3/86 (3.5%)	4	0/82 (0%)	0
Emphysema	0/86 (0%)	0	1/82 (1.2%)	1
Interstitial lung disease	1/86 (1.2%)	1	0/82 (0%)	0
Pleural effusion	0/86 (0%)	0	1/82 (1.2%)	1
Pneumonitis	0/86 (0%)	0	1/82 (1.2%)	2
Pulmonary embolism	0/86 (0%)	0	1/82 (1.2%)	1
Surgical and medical procedures
Ureteral stent insertion	1/86 (1.2%)	1	0/82 (0%)	0
Other (Not Including Serious) Adverse Events
	Rogaratinib (BAY1163877)		Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	85/86 (98.8%)		77/82 (93.9%)
Blood and lymphatic system disorders
Anaemia	11/86 (12.8%)	17	28/82 (34.1%)	66
Neutropenia	3/86 (3.5%)	6	19/82 (23.2%)	30
Eye disorders
Dry eye	5/86 (5.8%)	5	3/82 (3.7%)	3
Detachment of retinal pigment epithelium	7/86 (8.1%)	16	0/82 (0%)	0
Subretinal fluid	7/86 (8.1%)	8	0/82 (0%)	0
Gastrointestinal disorders
Abdominal pain	15/86 (17.4%)	18	13/82 (15.9%)	27
Constipation	25/86 (29.1%)	31	29/82 (35.4%)	54
Diarrhoea	48/86 (55.8%)	92	18/82 (22%)	19
Dry mouth	10/86 (11.6%)	15	2/82 (2.4%)	2
Mouth ulceration	5/86 (5.8%)	7	3/82 (3.7%)	3
Nausea	27/86 (31.4%)	38	20/82 (24.4%)	38
Stomatitis	10/86 (11.6%)	15	10/82 (12.2%)	14
Vomiting	15/86 (17.4%)	19	18/82 (22%)	26
General disorders
Asthenia	25/86 (29.1%)	52	19/82 (23.2%)	40
Fatigue	21/86 (24.4%)	32	28/82 (34.1%)	41
Mucosal inflammation	7/86 (8.1%)	20	8/82 (9.8%)	12
Oedema peripheral	8/86 (9.3%)	9	10/82 (12.2%)	13
Pyrexia	12/86 (14%)	15	10/82 (12.2%)	14
Infections and infestations
Conjunctivitis	5/86 (5.8%)	8	3/82 (3.7%)	3
Influenza	5/86 (5.8%)	5	0/82 (0%)	0
Paronychia	7/86 (8.1%)	8	0/82 (0%)	0
Urinary tract infection	12/86 (14%)	12	8/82 (9.8%)	13
Investigations
Alanine aminotransferase increased	13/86 (15.1%)	22	2/82 (2.4%)	4
Aspartate aminotransferase increased	10/86 (11.6%)	16	2/82 (2.4%)	3
Blood creatinine increased	11/86 (12.8%)	18	3/82 (3.7%)	6
Gamma-glutamyltransferase increased	5/86 (5.8%)	6	0/82 (0%)	0
Lipase increased	9/86 (10.5%)	25	3/82 (3.7%)	11
Neutrophil count decreased	0/86 (0%)	0	14/82 (17.1%)	22
Weight decreased	10/86 (11.6%)	11	6/82 (7.3%)	7
White blood cell count decreased	0/86 (0%)	0	5/82 (6.1%)	5
Blood alkaline phosphatase increased	12/86 (14%)	14	2/82 (2.4%)	3
Calcium phosphate product increased	8/86 (9.3%)	10	0/82 (0%)	0
Metabolism and nutrition disorders
Hyperkalaemia	8/86 (9.3%)	11	6/82 (7.3%)	14
Hyperphosphataemia	39/86 (45.3%)	79	0/82 (0%)	0
Hyponatraemia	6/86 (7%)	9	5/82 (6.1%)	7
Decreased appetite	36/86 (41.9%)	55	21/82 (25.6%)	25
Musculoskeletal and connective tissue disorders
Arthralgia	9/86 (10.5%)	12	7/82 (8.5%)	7
Back pain	8/86 (9.3%)	8	8/82 (9.8%)	9
Myalgia	5/86 (5.8%)	6	10/82 (12.2%)	12
Pain in extremity	7/86 (8.1%)	10	4/82 (4.9%)	4
Nervous system disorders
Dysgeusia	13/86 (15.1%)	14	5/82 (6.1%)	6
Headache	6/86 (7%)	7	4/82 (4.9%)	5
Neuropathy peripheral	3/86 (3.5%)	4	10/82 (12.2%)	12
Peripheral sensory neuropathy	1/86 (1.2%)	1	10/82 (12.2%)	14
Psychiatric disorders
Insomnia	5/86 (5.8%)	5	4/82 (4.9%)	4
Renal and urinary disorders
Haematuria	9/86 (10.5%)	13	6/82 (7.3%)	8
Respiratory, thoracic and mediastinal disorders
Cough	4/86 (4.7%)	6	6/82 (7.3%)	7
Dyspnoea	3/86 (3.5%)	3	5/82 (6.1%)	6
Epistaxis	10/86 (11.6%)	10	1/82 (1.2%)	1
Skin and subcutaneous tissue disorders
Alopecia	20/86 (23.3%)	23	24/82 (29.3%)	26
Dry skin	7/86 (8.1%)	9	2/82 (2.4%)	2
Nail discolouration	6/86 (7%)	8	0/82 (0%)	0
Palmar-plantar erythrodysaesthesia syndrome	7/86 (8.1%)	10	0/82 (0%)	0
Rash	7/86 (8.1%)	9	3/82 (3.7%)	5
Onychomadesis	7/86 (8.1%)	8	0/82 (0%)	0
Nail toxicity	7/86 (8.1%)	12	0/82 (0%)	0
Vascular disorders
Hypotension	6/86 (7%)	6	1/82 (1.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.