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Ref Type Journal Article
PMID (37541273)
Authors Pant S, Schuler M, Iyer G, Witt O, Doi T, Qin S, Tabernero J, Reardon DA, Massard C, Minchom A, Lugowska I, Carranza O, Arnold D, Gutierrez M, Winter H, Stuyckens K, Crow L, Najmi S, Hammond C, Thomas S, Santiago-Walker A, Triantos S, Sweiti H, Loriot Y, RAGNAR Investigators
Title Erdafitinib in patients with advanced solid tumours with FGFR alterations (RAGNAR): an international, single-arm, phase 2 study.
URL
Abstract Text FGFR alterations are reported across various malignancies and might act as oncogenic drivers in multiple histologies. Erdafitinib is an oral, selective pan-FGFR tyrosine kinase inhibitor with activity in FGFR-altered advanced urothelial carcinoma. We aimed to evaluate the safety and activity of erdafitinib in previously treated patients with FGFR-altered advanced solid tumours.The single-arm, phase 2 RAGNAR study was conducted at 156 investigative centres (hospitals or oncology practices that are qualified oncology study centres) across 15 countries. The study consisted of four cohorts based on tumour histology and patient age; the results reported in this Article are for the primary cohort of the study, defined as the Broad Panel Cohort, which was histology-agnostic. We recruited patients aged 12 years or older with advanced or metastatic tumours of any histology (except urothelial cancer) with predefined FGFR1-4 alterations (mutations or fusions according to local or central testing). Eligible patients had disease progression on at least one previous line of systemic therapy and no alternative standard therapy available to them, and an Eastern Cooperative Oncology Group performance status of 0-1 (or equivalent for adolescents aged 12-17 years). Patients received once-daily oral erdafitinib (8 mg/day with provision for pharmacodynamically guided up-titration to 9 mg/day) on a continuous 21-day cycle until disease progression or intolerable toxicity. The primary endpoint was objective response rate by independent review committee according to Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1, or Response Assessment In Neuro-Oncology (RANO). The primary analysis was conducted on the treated population of the Broad Panel Cohort. This ongoing study is registered with ClinicalTrials.gov, number NCT04083976.Patients were recruited between Dec 5, 2019, and Feb 15, 2022. Of 217 patients treated with erdafitinib, 97 (45%) patients were female and 120 (55%) were male. The data cutoff was Aug 15, 2022. At a median follow-up of 17·9 months (IQR 13·6-23·9), an objective response was observed in 64 (30% [95% CI 24-36]) of 217 patients across 16 distinct tumour types. The most common grade 3 or higher treatment-emergent adverse events related to erdafitinib were stomatitis (25 [12%]), palmar-plantar erythrodysaesthesia syndrome (12 [6%]), and hyperphosphataemia (11 [5%]). The most commonly occurring serious treatment-related adverse events (grade 3 or higher) were stomatitis in four (2%) patients and diarrhoea in two (1%). There were no treatment-related deaths.RAGNAR results show clinical benefit for erdafitinib in the tumour-agnostic setting in patients with advanced solid tumours with susceptible FGFR alterations who have exhausted other treatment options. These results support the continued development of FGFR inhibitors in patients with advanced solid tumours.Janssen Research & Development.

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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
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
FGFR2 W72C missense unknown FGFR2 W72C lies within Ig-like C2-type domain 1 of the Fgfr2 protein (UniProt.org). W72C has been identified in the scientific literature (PMID: 37541273), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Mar 2024).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR2 act mut Advanced Solid Tumor predicted - sensitive Erdafitinib Phase II Actionable In a Phase II trial (RAGNAR), Balversa (erdafitinib) treatment resulted in an objective response rate of 29.5% (64/217, 6 complete and 58 partial responses), a disease control rate of 74%, clinical benefit rate of 46%, a median duration of response of 6.9 months, median progression-free survival of 4.2 months, and median overall survival of 10.7 months in patients with advanced solid tumors harboring FGFR1, FGFR2, or FGFR3 mutations or fusions (PMID: 37541273; NCT04083976). 37541273
FGFR2 W72C FGFR2 E565A salivary gland cancer predicted - sensitive Erdafitinib Case Reports/Case Series Actionable In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in a complete response with a duration of response of 9.69 months in a patient with salivary gland cancer harboring FGFR2 E565A and W72C (PMID: 37541273; NCT04083976). 37541273
FGFR3 R248C breast cancer predicted - sensitive Erdafitinib Case Reports/Case Series Actionable In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in a partial response with a duration of response of 12.75 months in a patient with breast cancer harboring FGFR3 R248C (PMID: 37541273; NCT04083976). 37541273
FGFR1 fusion Advanced Solid Tumor predicted - sensitive Erdafitinib Phase II Actionable In a Phase II trial (RAGNAR), Balversa (erdafitinib) treatment resulted in an objective response rate of 29.5% (64/217, 6 complete and 58 partial responses), a disease control rate of 74%, clinical benefit rate of 46%, a median duration of response of 6.9 months, median progression-free survival of 4.2 months, and median overall survival of 10.7 months in patients with advanced solid tumors harboring FGFR1, FGFR2, or FGFR3 mutations or fusions (PMID: 37541273; NCT04083976). 37541273
FGFR2 C382R head and neck squamous cell carcinoma predicted - sensitive Erdafitinib Case Reports/Case Series Actionable In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in a partial response with a duration of response of 2.79 months in a patient with squamous cell head and neck cancer harboring FGFR2 C382R (PMID: 37541273; NCT04083976). 37541273
FGFR2 Y375C lung non-squamous non-small cell carcinoma predicted - sensitive Erdafitinib Case Reports/Case Series Actionable In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in a complete response with a duration of response of 5.59 months in a patient with non-squamous non-small cell lung cancer harboring FGFR2 Y375C (PMID: 37541273; NCT04083976). 37541273
FGFR3 fusion Advanced Solid Tumor predicted - sensitive Erdafitinib Phase II Actionable In a Phase II trial (RAGNAR), Balversa (erdafitinib) treatment resulted in an objective response rate of 29.5% (64/217, 6 complete and 58 partial responses), a disease control rate of 74%, clinical benefit rate of 46%, a median duration of response of 6.9 months, median progression-free survival of 4.2 months, and median overall survival of 10.7 months in patients with advanced solid tumors harboring FGFR1, FGFR2, or FGFR3 mutations or fusions (PMID: 37541273; NCT04083976). 37541273
FGFR3 S249C head and neck squamous cell carcinoma predicted - sensitive Erdafitinib Case Reports/Case Series Actionable In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in a partial response with a duration of response of 2.89 months in a patient with squamous cell head and neck cancer harboring FGFR3 S249C (PMID: 37541273; NCT04083976). 37541273
FGFR3 S249C ovarian cancer predicted - sensitive Erdafitinib Case Reports/Case Series Actionable In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in a partial response with a duration of response of 5.55 months in a patient with ovarian cancer harboring FGFR3 S249C (PMID: 37541273; NCT04083976). 37541273
FGFR1 act mut Advanced Solid Tumor predicted - sensitive Erdafitinib Phase II Actionable In a Phase II trial (RAGNAR), Balversa (erdafitinib) treatment resulted in an objective response rate of 29.5% (64/217, 6 complete and 58 partial responses), a disease control rate of 74%, clinical benefit rate of 46%, a median duration of response of 6.9 months, median progression-free survival of 4.2 months, and median overall survival of 10.7 months in patients with advanced solid tumors harboring FGFR1, FGFR2, or FGFR3 mutations or fusions (PMID: 37541273; NCT04083976). 37541273
FGFR3 act mut Advanced Solid Tumor predicted - sensitive Erdafitinib Phase II Actionable In a Phase II trial (RAGNAR), Balversa (erdafitinib) treatment resulted in an objective response rate of 29.5% (64/217, 6 complete and 58 partial responses), a disease control rate of 74%, clinical benefit rate of 46%, a median duration of response of 6.9 months, median progression-free survival of 4.2 months, and median overall survival of 10.7 months in patients with advanced solid tumors harboring FGFR1, FGFR2, or FGFR3 mutations or fusions (PMID: 37541273; NCT04083976). 37541273
FGFR2 C382R breast cancer predicted - sensitive Erdafitinib Case Reports/Case Series Actionable In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in a partial response with a duration of response of 14.32 months in a patient with breast cancer harboring FGFR2 C382R (PMID: 37541273; NCT04083976). 37541273
FGFR3 S249C lung squamous cell carcinoma predicted - sensitive Erdafitinib Case Reports/Case Series Actionable In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in a partial response with a duration of response of 9.03 months in a patient with squamous non-small cell lung cancer harboring FGFR3 S249C (PMID: 37541273; NCT04083976). 37541273
FGFR2 Y375C endometrial cancer predicted - sensitive Erdafitinib Case Reports/Case Series Actionable In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in a partial response with a duration of response of 6.9 months in a patient with endometrial cancer harboring FGFR2 Y375C (PMID: 37541273; NCT04083976). 37541273
FGFR2 C382R endometrial cancer predicted - sensitive Erdafitinib Case Reports/Case Series Actionable In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in partial response in two patients with endometrial cancer harboring FGFR2 C382R, with a duration of response of 23.72 months and 2.79 months, respectively (PMID: 37541273; NCT04083976). 37541273
FGFR1 K656E low grade glioma predicted - sensitive Erdafitinib Case Reports/Case Series Actionable In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in a complete response with a duration of response of 21.68 months in a patient with low grade glioma harboring FGFR1 K656E (PMID: 37541273; NCT04083976). 37541273
FGFR2 Y375C salivary gland cancer predicted - sensitive Erdafitinib Case Reports/Case Series Actionable In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in a complete response with a duration of response of 5.75 months in one patient and a partial response with a duration of response of 13.47 months in another patient, both with salivary gland cancer harboring FGFR2 Y375C (PMID: 37541273; NCT04083976). 37541273
FGFR2 fusion Advanced Solid Tumor predicted - sensitive Erdafitinib Phase II Actionable In a Phase II trial (RAGNAR), Balversa (erdafitinib) treatment resulted in an objective response rate of 29.5% (64/217, 6 complete and 58 partial responses), a disease control rate of 74%, clinical benefit rate of 46%, a median duration of response of 6.9 months, median progression-free survival of 4.2 months, and median overall survival of 10.7 months in patients with advanced solid tumors harboring FGFR1, FGFR2, or FGFR3 mutations or fusions (PMID: 37541273; NCT04083976). 37541273
FGFR2 C382R cholangiocarcinoma predicted - sensitive Erdafitinib Case Reports/Case Series Actionable In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in a partial response with a duration of response of 15.11 months in a patient with cholangiocarcinoma harboring FGFR2 C382R (PMID: 37541273; NCT04083976). 37541273