Missing content? – Request curation!
Request curation for specific Genes, Variants, or PubMed publications.
Have questions, comments, or suggestions? - Let us know!
Email us at : ckbsupport@jax.org
Ref Type | Journal Article | ||||||||||||
PMID | (31502117) | ||||||||||||
Authors | Kim SB, Meric-Bernstam F, Kalyan A, Babich A, Liu R, Tanigawa T, Sommer A, Osada M, Reetz F, Laurent D, Wittemer-Rump S, Berlin J | ||||||||||||
Title | First-in-Human Phase I Study of Aprutumab Ixadotin, a Fibroblast Growth Factor Receptor 2 Antibody-Drug Conjugate (BAY 1187982) in Patients with Advanced Cancer. | ||||||||||||
|
|||||||||||||
URL | |||||||||||||
Abstract Text | Fibroblast growth factor receptor (FGFR) 2 is overexpressed in several tumor types, including triple-negative breast cancer and gastric cancer, both of which have a high unmet medical need. Aprutumab ixadotin (BAY 1187982) is the first antibody-drug conjugate (ADC) to target FGFR2 and the first to use a novel auristatin-based payload.This first-in-human trial was conducted to determine the safety, tolerability, and maximum tolerated dose (MTD) of aprutumab ixadotin in patients with advanced solid tumors from cancer indications known to be FGFR2-positive.In this open-label, multicenter, phase I dose-escalation trial (NCT02368951), patients with advanced solid tumors received escalating doses of aprutumab ixadotin (starting at 0.1 mg/kg body weight), administered intravenously on day 1 of every 21-day cycle. Primary endpoints included safety, tolerability, and the MTD of aprutumab ixadotin; secondary endpoints were pharmacokinetic evaluation and tumor response to aprutumab ixadotin.Twenty patients received aprutumab ixadotin across five cohorts, at doses of 0.1-1.3 mg/kg. The most common grade ≥ 3 drug-related adverse events were anemia, aspartate aminotransferase increase, proteinuria, and thrombocytopenia. Dose-limiting toxicities were thrombocytopenia, proteinuria, and corneal epithelial microcysts, and were only seen in the two highest dosing cohorts. The MTD was determined to be 0.2 mg/kg due to lack of quantitative data following discontinuations at 0.4 and 0.8 mg/kg doses. One patient had stable disease; no responses were reported.Aprutumab ixadotin was poorly tolerated, with an MTD found to be below the therapeutic threshold estimated preclinically; therefore, the trial was terminated early. CLINICALTRIALS.NCT02368951. |
Molecular Profile | Treatment Approach |
---|
Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
---|
Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
---|---|---|---|
BAY1179470 | BAY1179470 | 0 | 0 |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
BAY1179470 | BAY 1179470|BAY-1179470|Aprutumab | FGFR2 Antibody 3 | BAY1179470 (Aprutumab) is an FGFR2 monoclonal antibody, which causes receptor internalization and degradation, thereby possibly inhibiting proliferation and promoting apoptosis in cancer cells (Cancer Res October 1, 2014 74; DDT02-01, PMID: 31502117). |
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 |
---|