Delving into the Latest Updates on Rogaratinib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

BAY 1163877盐酸盐

Target

FGFRs

Mechanism

FGFRs antagonists(Fibroblast growth factor receptors antagonists)

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication-

Inactive Indication

FGFR mutation-related tumorsFGFR positive Transitional Cell CarcinomaLocally Advanced Urothelial Carcinoma+ [4]

Originator Organization

Bayer AG

Active Organization-

Inactive Organization

Bayer AGCorden Pharma GmbH

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

RegulationSpecial Review Project (CN)

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Structure

Molecular FormulaC23H26N6O3S

InChIKeyHNLRRJSKGXOYNO-UHFFFAOYSA-N

CAS Registry1443530-05-9

This phase II trial studies the effect of rogaratinib in treating patients with sarcoma with a change in a group of proteins called fibroblast growth factor receptors (FGFRs) or SDH-deficient gastrointestinal stromal tumor (GIST). Rogaratinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Start Date03 May 2021

Sponsor / Collaborator

National Cancer Institute

NCT04483505 / CompletedPhase 1IIT

Rogaratinib, Palbociclib and Fulvestrant in Advanced Hormone Receptor Positive, FGFR1/2/3-positive Breast Cancer: Phase I Clinical Trial Plus an Expansion Cohort

This study is an open, multicenter, prospective phase I dose escalation clinical trial followed by an expansion cohort. The aim of this study is to asses the Recommended Phase 2 Dose (R2PD) and the safety profile, among other efficacy, in FGFR1/2/3 positive, hormone receptor-positive breast cancer (HRPBC) patients with metastatic disease after progression to the combination of an aromatase inhibitor plus palbociclib, abemaciclib or ribociclib, according RECIST 1.1 criteria.

Start Date25 Nov 2020

Sponsor / Collaborator

Pfizer Inc.

[+2]

NCT04040725 / WithdrawnPhase 2IIT

Phase II Clinical Trial of Rogaratinib for High Risk Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus Calmette-Guerin (BCG) With FGFR1 or FGFR3 Gene Overexpression: The Bladder Cancer Signal Seeking Trial (BLASST)-3

This research study is studying the safety, tolerability, and tumor activity of the study drug known as rogaratinib as a possible treatment for bladder cancer.

Start Date27 Nov 2019

Sponsor / Collaborator

Dana-Farber Cancer Institute, Inc.

[+1]

100 Clinical Results associated with Rogaratinib

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100 Translational Medicine associated with Rogaratinib

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100 Patents (Medical) associated with Rogaratinib

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10

Literatures (Medical) associated with Rogaratinib

19 Sep 2024·JAMA oncology

Rogaratinib Plus Atezolizumab in Cisplatin-Ineligible Patients With FGFR RNA-Overexpressing Urothelial Cancer: The FORT-2 Phase 1b Nonrandomized Clinical Trial.

Article

Author: Zhou, Yinghui ; Gajate, Pablo ; Sweis, Randy F ; Bao, Weichao ; de Braud, Filippo ; Maruzzo, Marco ; Grünwald, Viktor ; Morales-Barrera, Rafael ; Rosenberg, Jonathan E ; Penel, Nicolas ; Lee, Jae-Lyun ; Necchi, Andrea ; Ellinghaus, Peter ; Meran, Johannes ; Ishida, Tatiane Cristine

ImportanceThe oral pan-fibroblast growth factor receptor inhibitor rogaratinib previously demonstrated encouraging safety and efficacy in a phase 1 study of patients with urothelial cancer (UC) overexpressing FGFR messenger RNA (mRNA).ObjectiveTo evaluate the safety, pharmacokinetics, and preliminary efficacy of rogaratinib in combination with the programmed cell death 1 ligand 1 (PD-L1) inhibitor atezolizumab in cisplatin-ineligible patients with FGFR mRNA-positive, locally advanced/metastatic UC.Design, Setting, and ParticipantsThe FORT-2 nonrandomized clinical trial was an open-label, single-arm, multicenter study conducted between May 15, 2018, and July 16, 2021, in 30 centers across Asia, Europe, and North America. Eligible patients had locally advanced/metastatic UC with FGFR1/3 mRNA overexpression and were ineligible for cisplatin-based chemotherapy. The data analysis was completed from July 2022 to September 2022.InterventionsPatients received rogaratinib 600 mg or rogaratinib 800 mg twice daily in combination with intravenous atezolizumab 1200 mg every 21 days.Main Outcomes and MeasuresPrimary end points included safety, tolerability, and the recommended phase 2 dose (RP2D) of rogaratinib in combination with atezolizumab.ResultsAmong 153 patients screened, 73 (48%) had tumors with FGFR1/3 mRNA overexpression, and 37 patients were enrolled and treated (median [range] age, 75.0 [47.0-85.0] years; 32 [87%] male). The most common treatment-emergent adverse events (TEAEs) included diarrhea in 23 patients (62%), hyperphosphatemia in 19 (51%), and fatigue in 15 (41%). Grade 3 or higher TEAEs were reported in 27 patients (73%), and 4 grade 5 TEAEs were reported, though unrelated to treatment. The RP2D was rogaratinib 600 mg in combination with atezolizumab 1200 mg. At the RP2D, the overall response rate was 53.8% in the rogaratinib 600 mg group, including 4 patients (15%) with complete responses; 12 responders (86%) did not have an FGFR3 gene alteration, and 11 (79%) had low PD-L1 expression.Conclusions and RelevanceIn this phase 1b nonrandomized clinical trial, rogaratinib plus atezolizumab demonstrated a manageable safety profile, with no unexpected safety signals. Efficacy for this combination at the RP2D was observed in tumors with low PD-L1 and was not dependent on FGFR3 gene alterations, suggesting broad potential benefit for patients with locally advanced/metastatic UC and FGFR mRNA overexpression.Trial RegistrationClinicalTrials.gov Identifier: NCT03473756.

20 Jan 2023·Journal of Clinical Oncology

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

Article

Author: Quinn, David I. ; Ellinghaus, Peter ; Bellmunt, Joaquim ; Pápai, Zsuzsanna ; Lu, Chengxing ; Petrylak, Daniel P. ; Lee, Jae-Lyun ; Necchi, Andrea ; Rosenbaum, Eli ; Coppieters, Sabine ; Nakajima, Keiko ; Joly, Florence ; van der Heijden, Michiel S. ; Nishiyama, Hiroyuki ; Sternberg, Cora N. ; Sierecki, Mitchell ; García del Muro, Xavier ; Ishida, Tatiane Cristine ; Li, Jian-Ri ; Bao, Weichao ; Penel, Nicolas ; Gurney, Howard ; Pang, See-Tong

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.

01 Jan 2023·Frontiers in immunology

Treatment approaches for FGFR-altered urothelial carcinoma: targeted therapies and immunotherapy.

Review

Author: Benjamin, David J ; Hsu, Robert

The treatment of metastatic urothelial carcinoma has dramatically changed over the past decade with the approval of several therapies from multiple drug classes including immune checkpoint inhibitors, targeted therapies, and antibody drug conjugates. Although next generation sequencing of urothelial carcinoma has revealed multiple recurring mutations, only one targeted therapy has been developed and approved to date. Erdafitinib, a pan-fibroblast growth factor receptor (FGFR) inhibitor, has been approved for treating patients with select FGFR2 and FGFR3 alterations and fusions since 2019. Since then, emerging data has demonstrated efficacy of combining erdafitinib with immunotherapy in treating FGFR-altered urothelial carcinoma. Ongoing trials are evaluating the use of erdafitinib in non-muscle invasive urothelial carcinoma as well as in combination with enfortumab vedotin in the metastatic setting, while other FGFR targeted agents such as infigratinib, AZD4547, rogaratinib and pemigatinib continue to be in development. Future challenges will include strategies to overcome FGFR acquired resistance and efficacy and safety of combination therapies with erdafitinib and other FGFR targeted agents.

100 Deals associated with Rogaratinib

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15078

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Locally Advanced Urothelial Carcinoma	Phase 3	GB	Bayer AG	31 May 2018
Locally Advanced Urothelial Carcinoma	Phase 3	TW	Bayer AG	31 May 2018
Locally Advanced Urothelial Carcinoma	Phase 3	NL	Bayer AG	31 May 2018
Locally Advanced Urothelial Carcinoma	Phase 3	SE	Bayer AG	31 May 2018
Locally Advanced Urothelial Carcinoma	Phase 3	FI	Bayer AG	31 May 2018
Locally Advanced Urothelial Carcinoma	Phase 3	FR	Bayer AG	31 May 2018
Locally Advanced Urothelial Carcinoma	Phase 3	IL	Bayer AG	31 May 2018
Locally Advanced Urothelial Carcinoma	Phase 3	HK	Bayer AG	31 May 2018
Locally Advanced Urothelial Carcinoma	Phase 3	IE	Bayer AG	31 May 2018
Locally Advanced Urothelial Carcinoma	Phase 3	PT	Bayer AG	31 May 2018

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03473756 (FORT-2, ASCO2021) Manual	Phase 1	Metastatic urothelial carcinoma First line FGFR Positive	26	atezolizumab+rogaratinib	(jkubcvwypz) = The RP2D for R+A was 600 mg BID dcgsmctlet (hecahkodhp ) View more	Positive	20 May 2021
NCT03473756 (FORT-2, ASCO2021) Manual	Phase 1	Metastatic urothelial carcinoma First line FGFR Positive	26	atezolizumab+rogaratinib (low/negative PD-L1 protein and FGFR3 mRNA overexpression without mutation)		Positive	20 May 2021
NCT03473756 (FORT-2, ASCO2020)	Phase 1/2	Metastatic urothelial carcinoma First line	27	Rogaratinib 600 mg + Atezolizumab	(mibajytwno) = 63% zmpikscqku (feqbqiqegd ) View more	Positive	25 May 2020
NCT01976741 (ASCO_GU2020)	Phase 1	Neoplasms	74	Rogaratinib 800 mg po BID	(frjolzdrgv) = The most common treatment-emergent adverse events (TEAEs) are shown in the Table. The most common drug-related TEAEs (any grade) were diarrhea (52.7%), increased blood phosphorus (41.9%), and decreased appetite and dry mouth (31.1% each). No ocular toxicities were reported. Increased blood creatinine and acute kidney injury (AKI), regardless of relatedness, were reported in 16.2% and 2.7% of pts, respectively; 1 case of AKI was confirmed as acute tubular necrosis. hvtyboixja (prrfihhpeb )	Positive	19 Feb 2020
NCT01976741 (Pubmed)	Phase 1	FGFR mutation-related tumors	866	Rogaratinib	(xumcngpnuk) = woquruiyob dfcxxrqpbl (mahppssdhl, 8·6 - 23·5)	-	01 Oct 2019
NCT03762122 (ASCO2019)	Phase 2	Non-Small Cell Lung Cancer	260	Rogaratinib 800 mg BID	(yazolljzax) = 35% zppctkxcna (yvpjcimmzy ) View more	Positive	26 May 2019
NCT01976741 (ASCO2018)	Phase 1	Advanced Urothelial Carcinoma	219	Rogaratinib 800mg twice daily	(tvqpzczjiz) = swogicndfx uafyqnnkfl (ovinythdub ) View more	Positive	01 Jun 2018
NCT01976741 (ASCO_GU2018)	Phase 1	Advanced Urothelial Carcinoma	219	Rogaratinib 800mg	(vlvqlbgxjm) = 49% tmqdsljfny (xhaeeqpkay ) View more	-	26 Feb 2018