FORT-1: Phase II/III Study of Rogaratinib Versus Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Carcinoma Selected Based on FGFR1/3 mRNA Expression

PURPOSE

Rogaratinib, an oral pan-fibroblast growth factor receptor (FGFR1-4) inhibitor, showed promising phase I efficacy and safety in patients with advanced urothelial carcinoma (UC) with FGFR1-3 mRNA overexpression. We assessed rogaratinib efficacy and safety versus chemotherapy in patients with FGFR mRNA-positive advanced/metastatic UC previously treated with platinum chemotherapy.

METHODS

FORT-1 (ClinicalTrials.gov identifier: NCT03410693) was a phase II/III, randomized, open-label trial. Patients with FGFR1/3 mRNA-positive locally advanced or metastatic UC with ≥ 1 prior platinum-containing regimen were randomly assigned (1:1) to rogaratinib (800 mg orally twice daily, 3-week cycles; n = 87) or chemotherapy (docetaxel 75 mg/m², paclitaxel 175 mg/m², or vinflunine 320 mg/m² intravenously once every 3 weeks; n = 88). The primary end point was overall survival, with objective response rate (ORR) analysis planned following phase II accrual. Because of comparable efficacy between treatments, enrollment was stopped before progression to phase III; a full interim analysis of phase II was completed.

RESULTS

ORRs were 20.7% (rogaratinib, 18/87; 95% CI, 12.7 to 30.7) and 19.3% (chemotherapy, 17/88; 95% CI, 11.7 to 29.1). Median overall survival was 8.3 months (95% CI, 6.5 to not estimable) and 9.8 months (95% CI, 6.8 to not estimable; hazard ratio, 1.11; 95% CI, 0.71 to 1.72; P = .67). Grade 3/4 events occurred in 37 (43.0%)/4 (4.7%) patients and 32 (39.0%)/15 (18.3%), respectively. No rogaratinib-related deaths occurred. Exploratory analysis of patients with FGFR3 DNA alterations showed ORRs of 52.4% (11/21; 95% CI, 29.8 to 74.3) for rogaratinib and 26.7% (4/15; 95% CI, 7.8 to 55.1) for chemotherapy.

CONCLUSION

To our knowledge, these are the first data to compare FGFR-directed therapy with chemotherapy in patients with FGFR-altered UC, showing comparable efficacy and manageable safety. Exploratory testing suggested FGFR3 DNA alterations in association with FGFR1/3 mRNA overexpression may be better predictors of rogaratinib response.

INTRODUCTION

Patients with locally advanced or metastatic urothelial carcinoma (UC) have high recurrence rates following first-line platinum-based chemotherapy and poor prognosis.^1,2 Second-line treatments include immunotherapy and antibody-drug conjugates, with three immune checkpoint inhibitors approved by the US Food and Drug Administration in this setting.^1-4 The pan-fibroblast growth factor receptor (FGFR) inhibitor erdafitinib is approved for patients with susceptible FGFR3 or FGFR2 alterations following a phase II study reporting a 40% objective response rate (ORR) and median progression-free survival (PFS) and overall survival (OS) of 5.5 and 13.8 months, respectively.^5,6 Despite new options, many patients do not benefit from immunotherapy,^1,2 and metastatic UC remains a deadly disease in patients who relapse or progress during first-line chemotherapy.

CONTEXT

• Key Objective

• This interim analysis of the phase II FORT-1 trial evaluated the efficacy and safety of the fibroblast growth factor receptor (FGFR) inhibitor rogaratinib versus chemotherapy in patients with advanced or metastatic urothelial carcinoma selected on the basis of overexpression of FGFR1 or FGFR3 mRNA previously treated with platinum chemotherapy.

• Knowledge Generated

• Comparable efficacy outcomes were observed with rogaratinib versus chemotherapy in patients selected on the basis of FGFR1/3 mRNA positivity. An exploratory analysis suggested that rogaratinib may yield greater antitumor benefit in patients with both FGFR3 mRNA overexpression and an FGFR DNA alteration, warranting further investigation.

• Relevance

• To our knowledge, these are the first reported data comparing FGFR-targeted therapy with standard-of-care chemotherapy in patients selected on the basis of FGFR mRNA-positive urothelial carcinoma.

Aberrant activation of FGFR signaling by genetic alterations affects tumorigenesis and progression of various cancers, including late-stage muscle-invasive UC.^7-9 Of the four known FGFR subtypes, FGFR3 mutations have been identified in up to 42% of all UCs, up to 20% of metastatic disease cases, and up to 15% of muscle-invasive bladder tumors.^9-12 However, one study showed that 42% of bladder tumors without a detectable FGFR3 DNA mutation had FGFR3 protein overexpression, suggesting that patients with wild-type or FGFR3-mutated tumors could benefit from FGFR-targeted therapies.¹¹ Activating mutations in PIK3CA and RAS have been associated with resistance to FGFR inhibition in solid tumors, including UC,^13-16 implying that patients with wild-type PIK3CA or RAS may demonstrate improved responses to FGFR inhibition.

Rogaratinib (Bayer AG, Berlin, Germany) is an oral FGFR1-4 inhibitor that showed promising efficacy and safety in a phase I study (ClinicalTrials.gov identifier: NCT01976741) of patients with advanced cancers selected on the basis of FGFR1-3 mRNA overexpression and/or FGFR3-activating mutations/translocations.¹⁷ ORR was 24% (12/51) in a subset of patients with advanced muscle-invasive UC. Retrospective analysis supported the association of PIK3CA or RAS mutations with resistance to FGFR inhibition.¹⁷

We present the results from an unplanned interim analysis of the phase II part of FORT-1 (ClinicalTrials.gov identifier: NCT03410693), a phase II/III, randomized, open-label study evaluating rogaratinib efficacy versus chemotherapy in patients with FGFR mRNA-positive advanced or metastatic UC previously treated with platinum chemotherapy.

METHODS

Study Design and Patients

This prospective, phase II, randomized, open-label, multicenter trial comprised FGFR testing, screening, treatment, and follow-up (Data Supplement, online only). The study was conducted at 161 academic medical centers/hospitals in Asia, Europe, North America, and Australia. FGFR testing was performed at the investigator's discretion ≤ 90 days before screening in patients age ≥ 18 years with locally advanced or metastatic UC, histologically or cytologically confirmed (including urinary bladder, renal pelvis, ureters, and urethra). Patients had to have an Eastern Cooperative Oncology Group performance status of 0 or 1 and availability of archival or fresh tumor biopsy. Only patients with FGFR1/3 mRNA-positive tumors (high expression of FGFR1 or FGFR3 mRNA) were eligible to continue screening (Data Supplement).

All patients provided written, informed consent. The study site designated Institutional Review Board or equivalent approved the Protocol (online only) before the start of the study, according to Good Clinical Practice guidelines and the Declaration of Helsinki.

Random Assignment

Eligible patients with FGFR1/3 mRNA-expressing tumors were randomly assigned 1:1 to rogaratinib or investigator-determined intravenous chemotherapy. Random assignment was stratified by the presence/absence of PIK3CA-/RAS-activating mutations, presence/absence of previous immunotherapy, and high/low modified four-factor Bellmunt risk score.¹⁸

Procedures

We centrally assessed FGFR1 or FGFR3 mRNA expression using in situ hybridization (RNAscope; developed by Advanced Cell Diagnostics, Newark, CA, in partnership with Leica Biosystems, Newcastle, United Kingdom), with high FGFR mRNA expression defined as an RNAscope score of 3+ or 4+.¹⁷ During FGFR testing, we centrally tested DNA from tumor biopsies for PIK3CA and/or RAS mutations using polymerase chain reaction–based clinical trial assays (LabCorp, Burlington, NC). Because of lower-than-expected prevalence of PIK3CA and/or RAS resistance mutations, we reconfirmed absence or presence in all enrolled patients using a targeted Illumina MiSeq panel (Illumina, Inc, San Diego, CA) performed by TARGOS Molecular Pathology GmbH (Kassel, Germany). Exploratory FGFR3 DNA mutation and fusion testing used the OmniSeq Comprehensive targeted next-generation sequencing panel (OmniSeq, Buffalo, NY), with a minor allele frequency cutoff of 5%.

The starting dose of rogaratinib was 800 mg orally twice daily in continuous 3-week cycles. Chemotherapy could include intravenous docetaxel 75 mg/m², paclitaxel 175 mg/m², or vinflunine 320 mg/m² once every 3 weeks. Patients continued treatment until radiologic or clinical disease progression, unacceptable toxicity, or withdrawal.

We centrally assessed tumors using Response Evaluation Criteria in Solid Tumors version 1.1 at baseline, every 6 weeks up to week 18, and every 9 weeks thereafter. Assessments continued for at least 30 days for patients who discontinued treatment without disease progression.

We collected blood samples for biomarker analyses at screening, before dosing on day 1 of each cycle, and within 14 days of discontinuation, and plasma samples for pharmacokinetic assessment in patients treated with rogaratinib on day 1 of cycles 1-5 before dosing and 0.5-1.5 hours after dosing.

Outcomes

The primary end point for the planned phase II/III study was OS. Secondary end points included PFS, ORR, disease control rate (DCR), duration of response, safety, and tolerability. Safety was assessed throughout the treatment period, within 14 days of discontinuation, and up to 30 days after the last study treatment, including evaluation for retinopathy. Grade ≥ 2 retinal disorders were considered of special interest and monitored throughout the study (Data Supplement). Treatment-emergent adverse events (TEAEs) were classified using Medical Dictionary for Regulatory Activities version 22.1 and graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.

Statistical Analyses

The phase II part of the study was designed to achieve 90% power to detect the difference in ORR between rogaratinib (assumed ORR = 30%) and chemotherapy (assumed ORR = 10%) in patients who were FGFR mRNA-positive with wild-type PIK3CA/RAS. Assuming a one-sided alpha of 0.1, a power of 90%, a mutation rate of approximately 25% for PIK3CA and RAS in the study population, and a random assignment ratio of 1:1, approximately 116 such patients were to be included in the planned analysis of ORR, on the basis of Fisher's exact test. phase II was planned to end after these first 116 enrolled patients completed 4.5 months of treatment, at which time the planned ORR analysis would be performed. Patients recruited to phase II were to automatically continue to phase III without interruption if futility was not demonstrated (Data Supplement).

We analyzed efficacy in all randomly assigned patients (full analysis set). The safety population comprised patients who received ≥ 1 dose of study treatment. ORR and DCR were compared using Fisher's exact test. Median OS and PFS were estimated using Kaplan-Meier methods. Hazard ratios and 95% CIs for OS and PFS were calculated using stratified Cox proportional hazards and a stratified log-rank test. Median follow-up time was calculated using the reverse Kaplan-Meier method.

Following a potential imbalance of deaths during the study period, the Data Monitoring Committee recommended a pause in enrollment and a reduction in the daily dose of rogaratinib from 800 to 600 mg twice daily for further evaluation. Because of similar efficacy between the treatment groups, the sponsor decided to stop further enrollment into the study on March 8, 2019. This report describes an interim analysis of efficacy and safety at a data cutoff date of November 25, 2019 (Data Supplement).

We performed a retrospective exploratory rescoring of the tumor samples from randomly assigned patients because of a higher-than-expected proportion of patients testing positive for tumors with high FGFR1 or FGFR3 mRNA expression (RNAscope score 3+ or 4+; Data Supplement). We analyzed the relationship between rogaratinib exposure and safety using logistic regression models (Data Supplement).

RESULTS

Patients

From May 31, 2018, to March 8, 2019, we tested 683 patients for FGFR1/3 mRNA overexpression and 664 (97.2%) had a valid test result. Of these, 456 (68.7%) had FGFR overexpression at initial testing; 175 of these patients met the screening eligibility criteria, with 87 randomly assigned to rogaratinib and 88 to chemotherapy (Data Supplement). Of the 82 patients treated with chemotherapy, 40 (48.8%) received vinflunine, 24 (29.3%) received paclitaxel, and 18 (22.0%) received docetaxel. Overall, 7.4% of patients had wild-type PIK3CA/RAS, 10.9% were confirmed to have PIK3CA and/or RAS mutations, and 17.7% were unknown (Table 1). A higher percentage of patients receiving rogaratinib had stage IV B disease at study entry (Table 1).

TABLE 1.

Patient Demographics and Baseline Cancer Characteristics

Treatment

At the cutoff date (median follow-up 10.8 months; 95% CI, 10.1 to 11.7), median treatment duration was 12.0 weeks (range, 2.1-40.7 weeks) with rogaratinib and 9.4 weeks (range, 0.1-39.1 weeks) with chemotherapy, corresponding to a median of four treatment cycles (range, 1-14 cycles) in both treatment groups. One patient (1.1%) assigned to rogaratinib and six (6.8%) assigned to chemotherapy did not receive treatment and were excluded from the safety analyses. Most patients receiving rogaratinib (83/86 [96.5%]) had a starting dose of 800 mg. At the analysis cutoff date, six patients (6.9%) were ongoing with rogaratinib and four (4.5%) were ongoing with chemotherapy. The most common primary reason for treatment discontinuation was disease progression, including radiologic progression in 53 patients (60.9%) receiving rogaratinib and 47 (53.4%) receiving chemotherapy, and clinical progression in zero and six (6.8%) patients, respectively.

Efficacy

In the overall population, ORRs of 20.7% (18/87) and 19.3% (17/88) were observed for patients assigned to rogaratinib and chemotherapy, respectively (rate difference = 1.4; one-sided P = .48), with similar DCRs between groups (Table 2). Efficacy was similar in patients whose FGFR expression was confirmed by retrospective exploratory rescoring compared with the overall population (Data Supplement). Of responders, 12/18 (66.7%) assigned to rogaratinib and 9/17 (52.9%) assigned to chemotherapy had previously received immunotherapy.

TABLE 2.

Objective Tumor Response (full analysis set)

Median duration of response was 4.9 months (95% CI, 3.5 to 9.1) with rogaratinib and 5.8 months (95% CI, 3.5 to 7.7) with chemotherapy. Median OS was 8.3 months (95% CI, 6.5 to not evaluable) with rogaratinib and 9.8 months (95% CI, 6.8 to not evaluable) with chemotherapy (one-sided P = .67; Fig 1A). Median PFS was similar (Fig 1B). No differences in ORR or DCR were observed in the subset of patients with confirmed PIK3CA and RAS mutations (Data Supplement).

FIG 1.

Kaplan-Meier curves of (A) OS and (B) PFS (full analysis set). Median (95% CI) from Kaplan-Meier estimates; P value is taken from stratified log-rank test; HR (95% CI) on the basis of stratified Cox proportional hazards model. HR, hazard ratio; NE, not evaluable; OS, overall survival; PFS, progression-free survival.

A post hoc analysis of patients with high FGFR3 mRNA expression identified 21/82 (25.6%) assigned to rogaratinib and 15/79 (19.0%) assigned to chemotherapy who also had FGFR3 DNA alterations (four unique hotspot mutations [FGFR3-G370C, FGFR3-R248C, FGFR3-S249C, and FGFR3-Y373C] and two unique fusions [FGFR3-TACC3v1 and FGFR3-TACC3v3]). Retrospective exploratory analysis showed higher ORRs for patients assigned to rogaratinib than to chemotherapy (Table 3). Median OS at the later data cutoff was not reached in either group in this subset of patients (Data Supplement).

TABLE 3.

Exploratory Analysis of Tumor Response by FGFR3 DNA Alteration (full analysis set)

Safety

Grade 3 TEAEs occurred in 37 patients (43.0%) receiving rogaratinib and 32 (39.0%) receiving chemotherapy; grade 4 events occurred in 4 (4.7%) and 15 (18.3%), respectively (Table 4). Grade ≥ 2 retinal disorders were reported in six patients (7.0%) with rogaratinib and zero patients with chemotherapy; events included retinal pigment epithelium detachment in three patients (3.5%; all grade 2) and chorioretinopathy (grade 2), retinopathy (grade 3), and serous retinopathy (grade 2) in one patient each (1.2%). Including grade 1 events, 26 patients (30.2%) receiving rogaratinib and three (3.7%) receiving chemotherapy experienced a retinal disorder (Data Supplement). TEAEs remained similar following rescoring of FGFR expression (Data Supplement). Table 5 summarizes drug-related TEAEs.

TABLE 4.

Summary of Most Common Any-Grade TEAEs Occurring in ≥ 10% of Patients in Either Treatment Group (safety analysis set^a)

TABLE 5.

Summary of Most Common Drug-Related Any-Grade TEAEs Occurring in ≥ 10% of Patients in Either Treatment Group (safety analysis set^a)

Grade 5 TEAEs occurred in 19 patients (11.3%), 14 of whom (16.3%) received rogaratinib and five of whom (6.1%) received chemotherapy. The most common grade 5 events with rogaratinib were general physical health deterioration (n = 3) and dyspnea (n = 3), with no events considered drug-related. One grade 5 event in a patient receiving chemotherapy (respiratory tract infection) was considered drug-related. Of patients with grade 5 TEAEs, 11/14 (78.6%) receiving rogaratinib and 4/5 (80.0%) receiving chemotherapy had stage IV B disease at study entry. The Data Supplement provides further details on deaths during the study.

An exploratory analysis showed no significant relationships between area under the curve from 0 to 12 hours at steady state and adverse events such as diarrhea, vomiting, nausea, fatigue, retinal disorder, nail disorder, and increased serum lipase, or between exposure and grade ≥ 3 TEAEs (Data Supplement).

The Data Supplement summarizes dose modifications (interruptions or reductions). The most common TEAEs leading to dose modification were hyperphosphatemia (n = 18 [20.9%]) and diarrhea (n = 10 [11.6%]) with rogaratinib, and neutropenia/decreased neutrophil count (n = 6 [7.3%]) and fatigue (n = 4 [4.9%]) with chemotherapy. TEAEs led to permanent discontinuation in 15 patients (17.4%) receiving rogaratinib, most commonly asthenia in four patients (4.7%), with all other events occurring in one patient each (1.2%), and nine patients (11.0%) receiving chemotherapy, most commonly constipation, fatigue, and peripheral neuropathy in two patients each (2.4%).

TEAE incidence was similar for those who received the planned rogaratinib dose of 800 mg twice daily or the reduced dose of 600 mg twice daily.

DISCUSSION

Interim results from the phase II part of the FORT-1 study of rogaratinib versus chemotherapy provide, to our knowledge, the first reported data comparing FGFR-targeted therapy with standard-of-care chemotherapy in patients selected for FGFR mRNA-positive UC, defined as overexpression of FGFR1 or FGFR3 mRNA.

This interim analysis of 175 patients revealed no significant differences in ORRs between patients assigned to rogaratinib or chemotherapy (20.7% and 19.3%, respectively). The ORR observed with rogaratinib is comparable with that in the subset of patients with UC selected on the basis of FGFR1-3 mRNA overexpression in the phase I study of rogaratinib (23.5%),¹⁷ and is in line with ORRs reported in early-phase trials of other pan-FGFR inhibitors in patients with UC with FGFR3 mutations.^19,20 Similarly, no significant differences in DCRs were observed in the rogaratinib and chemotherapy groups. The DCR observed with rogaratinib was slightly lower than that reported in other studies of early-phase FGFR inhibitors in patients with advanced UC selected on the basis of FGFR3 DNA alterations^19,20 and in the phase I study of rogaratinib (71% overall and 73% in the subset with UC).¹⁷

OS and PFS were not statistically different within the treatment groups. OS with rogaratinib in patients selected on the basis of high expression of FGFR1/3 mRNA was broadly similar to that reported with the FGFR1-3 inhibitor infigratinib in patients with advanced UC with FGFR3 genetic alterations (7.75 months), with a comparable duration of treatment.¹⁹ PFS was similar to that in the phase I study of rogaratinib (3.3 months).¹⁷ In a phase II trial of the pan-FGFR inhibitor erdafitinib in patients with platinum-refractory advanced UC selected on the basis of FGFR DNA alterations, median OS and PFS were 13.8 and 5.5 months, respectively.⁵ Our findings show that patient selection on the basis of FGFR1 or FGFR3 mRNA positivity alone does not lead to improved outcomes with rogaratinib versus chemotherapy.

Following a higher-than-expected proportion of patients having tumors with high FGFR1 and FGFR3 mRNA expression (69% in this study v 50% in the phase I study¹⁷), we performed a retrospective exploratory rescoring of tumor samples from randomly assigned patients; efficacy and safety were not significantly affected by this rescoring (Data Supplement). However, we cannot rule out the possibility that patients without high FGFR1 and FGFR3 mRNA expression were included in the study, potentially contributing to the limited objective responses with rogaratinib.

Because of the small proportion of patients with confirmed PIK3CA/RAS mutations, it was not possible to robustly test if wild-type PIK3CA/RAS was associated with improved responses to FGFR inhibition compared with patients with activating mutations. Previous observations linking PIK3CA- and RAS-activating mutations with resistance to FGFR inhibition in solid tumors, including UC,^13-16 indicate that this hypothesis may be worthy of investigation.

Retrospective exploratory analysis of patients positive for FGFR3 mRNA and with FGFR3 DNA alterations revealed a higher ORR with rogaratinib compared with the full analysis set (52.4% v 20.7%). An ORR of 40% was observed with erdafitinib in patients with advanced UC selected on the basis of FGFR DNA alterations.⁵ In our study, median OS was not reached in either group in patients with FGFR3 DNA alterations, but survival was slightly lower with rogaratinib compared with chemotherapy. However, these ORR and OS results should be interpreted with caution because of the small sample size and retrospective exploratory nature. Overall, the improved ORR with rogaratinib seen in this study in FGFR mRNA-positive patients with FGFR genetic DNA alterations is of interest and may warrant further evaluation.

GI toxicities were among the most commonly observed TEAEs, in line with the phase I study of rogaratinib¹⁷ and other studies of pan-FGFR inhibitors in patients with advanced UC.^5,19,20 Hyperphosphatemia was the second most common TEAE with rogaratinib and is considered an on-target effect of FGFR inhibition related to FGFR2/3 signaling^21,22; no grade ≥ 3 events were reported, and all cases of hyperphosphatemia resolved with treatment interruption and were without clinically relevant symptoms. Grade ≥ 2 retinal disorders were considered TEAEs of special interest and were reported in 7.0% of patients receiving rogaratinib compared with zero receiving chemotherapy; 30.2% of patients receiving rogaratinib and 3.7% receiving chemotherapy experienced retinal disorders of any grade. An exploratory analysis showed no significant relationships between rogaratinib exposure and TEAEs. Dose modifications were more frequent with rogaratinib than with chemotherapy, partly because of protocol-mandated modifications for hyperphosphatemia.

Grade 5 events were more common with rogaratinib than with chemotherapy (16.3% v 6.1%). Most grade 5 events across both groups were in patients with stage IV B disease at study entry, suggesting that these patients may have been at greater risk of TEAEs leading to death, irrespective of treatment group; the higher percentage of patients with stage IV B disease receiving rogaratinib may explain the slight imbalance in grade 5 events observed between groups. No grade 5 events were considered related to rogaratinib, and one case of grade 5 respiratory tract infection was attributed to chemotherapy. Potentially severe lung infection as a result of immune consequences is a known side effect of chemotherapy.²³

In conclusion, to our knowledge, these are the first reported data comparing FGFR-directed therapy with chemotherapy in patients with FGFR-altered UC. Rogaratinib demonstrated efficacy comparable with standard chemotherapy and a manageable safety profile. Prespecified efficacy criteria were not met for continuation to phase III in this population. An exploratory analysis suggested that rogaratinib may have greater antitumor benefit in patients with both FGFR3 mRNA overexpression and an FGFR DNA alteration, which warrants further investigation.

APPENDIX

TABLE A1.

FORT-1 Principal Investigators

DATA SHARING STATEMENT

Availability of the data underlying this publication will be determined according to Bayer's commitment to the EFPIA/PhRMA Principles for Responsible Clinical Trial Data Sharing. This pertains to scope, time point, and process of data access.

As such, Bayer commits to sharing upon request from qualified scientific and medical researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the United States and European Union as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 1, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct further research that can help advance medical science or improve patient care. Information on the Bayer criteria for listing studies and other relevant information is provided in the study sponsor's section of the portal.

Data access will be granted to anonymized patient-level data, protocols, and clinical study reports after approval by an independent scientific review panel. Bayer is not involved in the decisions made by the independent review panel. Bayer will take all necessary measures to ensure that patient privacy is safeguarded.

AUTHOR CONTRIBUTIONS

Conception and design: Cora N. Sternberg, Daniel P. Petrylak, Joaquim Bellmunt, Weichao Bao, Peter Ellinghaus, Chengxing Lu, Sabine Coppieters, Keiko Nakajima, Tatiane Cristine Ishida, David I. Quinn

Administrative support: Tatiane Cristine Ishida

Provision of study materials or patients: Cora N. Sternberg, Joaquim Bellmunt, Howard Gurney, Jae-Lyun Lee, Michiel S. van der Heijden, Nicolas Penel, See-Tong Pang, Jian-Ri Li, Xavier García del Muro, Florence Joly, David I. Quinn

Collection and assembly of data: Cora N. Sternberg, Joaquim Bellmunt, Hiroyuki Nishiyama, Howard Gurney, Jae-Lyun Lee, Michiel S. van der Heijden, See-Tong Pang, Jian-Ri Li, Xavier García del Muro, Peter Ellinghaus, Chengxing Lu, Sabine Coppieters, Keiko Nakajima, Tatiane Cristine Ishida, David I. Quinn

Data analysis and interpretation: Cora N. Sternberg, Joaquim Bellmunt, Hiroyuki Nishiyama, Andrea Necchi, Howard Gurney, Jae-Lyun Lee, Michiel S. van der Heijden, Eli Rosenbaum, Nicolas Penel, Xavier García del Muro, Florence Joly, Weichao Bao, Peter Ellinghaus, Chengxing Lu, Mitchell Sierecki, Sabine Coppieters, Keiko Nakajima, Tatiane Cristine Ishida, David I. Quinn

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

FORT-1: Phase II/III Study of Rogaratinib Versus Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Carcinoma Selected Based on FGFR1/3 mRNA Expression

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

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