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Ref Type Journal Article
PMID (30807645)
Authors Grünewald S, Politz O, Bender S, Héroult M, Lustig K, Thuss U, Kneip C, Kopitz C, Zopf D, Collin MP, Boemer U, Ince S, Ellinghaus P, Mumberg D, Hess-Stumpp H, Ziegelbauer K
Title Rogaratinib: A potent and selective pan-FGFR inhibitor with broad antitumor activity in FGFR-overexpressing preclinical cancer models.
Journal International journal of cancer
Vol 145
Issue 5
Date 2019 09 01
URL
Abstract Text Aberrant activation in fibroblast growth factor signaling has been implicated in the development of various cancers, including squamous cell lung cancer, squamous cell head and neck carcinoma, colorectal and bladder cancer. Thus, fibroblast growth factor receptors (FGFRs) present promising targets for novel cancer therapeutics. Here, we evaluated the activity of a novel pan-FGFR inhibitor, rogaratinib, in biochemical, cellular and in vivo efficacy studies in a variety of preclinical cancer models. In vitro kinase activity assays demonstrate that rogaratinib potently and selectively inhibits the activity of FGFRs 1, 2, 3 and 4. In line with this, rogaratinib reduced proliferation in FGFR-addicted cancer cell lines of various cancer types including lung, breast, colon and bladder cancer. FGFR and ERK phosphorylation interruption by rogaratinib treatment in several FGFR-amplified cell lines suggests that the anti-proliferative effects are mediated by FGFR/ERK pathway inhibition. Furthermore, rogaratinib exhibited strong in vivo efficacy in several cell line- and patient-derived xenograft models characterized by FGFR overexpression. The observed efficacy of rogaratinib strongly correlated with FGFR mRNA expression levels. These promising results warrant further development of rogaratinib and clinical trials are currently ongoing (ClinicalTrials.gov Identifiers: NCT01976741, NCT03410693, NCT03473756).

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Rogaratinib BAY 1163877|BAY-1163877|BAY1163877 FGFR Inhibitor (Pan) 24 Rogaratinib (BAY 1163877) is a small molecule pan-FGFR inhibitor, which reduces downstream signaling, potentially resulting in decreased tumor cell proliferation (PMID: 27429073, PMID: 29451369, PMID: 30807645, PMID: 31405822).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR2 amp FGFR2 over exp colon cancer sensitive Rogaratinib Preclinical - Cell line xenograft Actionable In a preclinical study, a colon cancer cell line xenograft model with FGFR2 amplification and FGFR2 overexpression demonstrated antitumor efficacy when treated with Rogaratinib (BAY 1163877), with a partial response in one of eight at one dose and five of eight at a different dose (PMID: 30807645). 30807645
FGFR1 over exp lung cancer predicted - sensitive Rogaratinib Preclinical - Pdx Actionable In a preclinical study, a lung cancer patient-derived xenograft (PDX) model with FGFR1 overexpression demonstrated decreased tumor volume when treated with Rogaratinib (BAY 1163877) (PMID: 30807645). 30807645
FGFR1 amp FGFR1 over exp lung cancer sensitive Docetaxel + Rogaratinib Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with Rogaratinib (BAY 1163877) and Taxotere (docetaxel) resulted in an increased percentage of partial responses from 40% to 70% and one complete response compared to Taxotere (docetaxel) alone in lung cancer cell line xenograft models with FGFR1 amplification and FGFR1 overexpression (PMID: 30807645). 30807645
FGFR1 amp FGFR1 over exp lung cancer sensitive Rogaratinib Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with Rogaratinib (BAY 1163877) in a lung cancer cell line xenograft model with FGFR1 amplification and FGFR1 overexpression resulted in inhibition of tumor growth (PMID: 30807645). 30807645
FGFR1 amp FGFR1 over exp lung cancer sensitive Carboplatin + Paclitaxel + Rogaratinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination therapy of Rogaratinib (BAY 1163877), Paraplatin (carboplatin), and Taxol (paclitaxel) resulted in an increased percentage of partial responses, from 30% to 70%, when compared to chemotherapy alone in lung cancer cell line xenograft models with FGFR1 amplification and FGFR1 overexpression (PMID: 30807645). 30807645
FGFR1 over exp lung cancer predicted - sensitive Docetaxel + Rogaratinib Preclinical - Pdx Actionable In a preclinical study, the combination of Rogaratinib (BAY 1163877) and Taxotere (docetaxel) resulted in improved inhibition of tumor growth and duration of response, leading to three complete responses and seven partial responses compared to Taxotere (docetaxel) alone, resulting in only six partial responses, in lung cancer patient-derived xenograft models with FGFR1 overexpression (n=10) (PMID: 30807645). 30807645
FGFR1 over exp colon cancer sensitive Rogaratinib Preclinical Actionable In a preclinical study, syngeneic colon cancer mouse models with FGFR1 over expression demonstrated antitumor activity when treated with Rogaratinib (BAY 1163877), with a partial response observed in 22% (2/9) and stable disease in one (PMID: 30807645). 30807645