phase 1/2 study of derazantinib (arq 087) in adult subjects with advanced solid tumors with fgfr genetic alterations

Conditions: Solid Tumor

Summary: this was an open-label, phase 1/2, dose escalation and signal finding study of derazantinib administered to patients with advanced solid tumors (part 1; dose escalation/food-effect cohorts) or with advanced solid tumors with fgfr genetic aberrations, including icca with fgfr2 gene fusion (part 2; expanded cohort, signal finding).


Eligibility criteria:
inclusion criteria: 1. signed written informed consent granted 2. men or women ≥18 years of age 3. histologically or cytologically confirmed, locally advanced, inoperable, or metastatic solid tumors. patients eligible for enrollment in the expanded cohort must have documented and/or confirmed fgfr genetic aberrations, including icca with fgfr2 gene fusion. 4. failure to respond to standard therapy, or for whom standard therapy does not exist. 5. evaluable or measurable disease 6. archival and/or fresh biopsy tissue samples must be available prior to the first dose of the study drug 7. life expectancy ≥ 12 weeks 8. eastern cooperative oncology group (ecog) performance status ≤ 2 9. hemoglobin (hgb) ≥ 9.0 g/dl 10. absolute neutrophil count (anc) ≥ 1.5 x 10\^9/l 11. platelet count ≥ 100 x 10\^9/l 12. total bilirubin ≤ 1.5 × upper limit of normal (uln) (≤ 2 x uln for patients with cholangiocarcinoma) 13. aspartate transaminase (ast) and alanine transaminase (alt) ≤ 3 × uln (≤ 5 x uln for patients with liver metastases) 14. serum creatinine ≤ 1.5 x uln or creatinine clearance \> 60 ml/min/1.73 m\^2 for patients with creatinine levels above institutional normal 15. albumin ≥ 2.8 g/dl 16. inr 0.8 to uln or ≤ 3 for patients receiving anticoagulant therapy 17. men or women of child-producing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoid intercourse during the study and for 90 days after the last dose of study drug 18. women of childbearing potential must have a negative serum pregnancy test during screening period and within 48 hours of the first dose of derazantinib. exclusion criteria: 1. anti-cancer therapy, such as chemotherapy, immunotherapy, hormonal, targeted therapy, or investigational agents within four weeks or five times of the drug half life, whichever is longer, of the first dose of derazantinib 2. major surgery or radiation therapy within four weeks of the first dose of derazantinib 3. previous treatment with fgfr inhibitors 4. history of allergic reactions attributed to compounds of similar chemical or biological composition as derazantinib 5. unable or unwilling to swallow the complete daily dose of derazantinib 6. clinically unstable central nervous system (cns) metastasis 7. history of myocardial infarction (mi) or congestive heart failure defined as class ii to iv per the new york heart association classification within 6 months of the first dose of derazantinib (mi occurring \>6 months of the first dose of derazantinib will be permitted) 8. significant gi disorder(s) that could interfere with the absorption, metabolism, or excretion of derazantinib (e.g. crohn's disease, ulcerative colitis, extensive gastric resection) 9. history and/or current evidence of clinically relevant ectopic mineralization/calcification 10. previous malignancy within 2 years prior to the first dose of derazantinib, except curatively treated non-melanoma skin cancer, carcinoma in-situ of the breast or cervix, or superficial bladder tumors 11. known human immunodeficiency virus (hiv) infection 12. concurrent uncontrolled illness not related to cancer, including but not limited to: * psychiatric illness/substance abuse/social situation that would limit compliance with study requirements. * uncontrolled diabetes mellitus 13. blood transfusion within 5 days of the blood draw being used to confirm eligibility 14. pregnant or breastfeeding

Keywords: fgfr arq 087 targeted therapy molecular therapy tyrosine kinase inhibitor tki receptor tyrosine kinase rtk biomarker phase 1 phase i solid tumor liver cancer hepatobiliary carcinoma biliary tract cancer cholangiocarcinoma intrahepatic cholangiocarcinoma fgfr inhibitor targeted fgfr kinase inhibitor pan-fgfr inhibitor selective fgfr inhibitor fgfr pathway fgfr signaling fibroblast growth factor fgfr1 fgfr2 fgfr3 fgfr4 fgf fgf19 fgf21 fgf23 fgfr mutation fgfr gene fusion fgfr gene translocation fgfr genetic aberration fgfr2 fusion fgfr2 translocation phase 1 clinical trial phase i clinical trial clinical oncology tumor tumour derazantinib mk-2921