safety, tolerability and pharmacokinetics of oral cpl304110, in adult subjects with advanced solid malignancies

Conditions: Gastric Cancer; Bladder Cancer; Squamous Non-small Cell Lung Cancer; Cholangiocarcinoma; Sarcoma; Endometrial Cancer; Other Solid Tumours

Summary: the purpose of the study is to determine to evaluate safety and tolerability of cpl304110 when administered once daily to adults with advanced solid malignancies.

01fgfr2018 is an open-label, multicentre, dose escalation study to assess safety, tolerability and pharmacokinetics of oral cpl304110, in adult subjects with advanced solid malignancies. the study consists of 3 parts: initial dose escalation (part 1 - without fgfr, fibroblast growth factor receptor, molecular aberrations), dose escalation (part 2 - with fgfr molecular aberrations) and dose extension (part 3 - with fgfr molecular aberrations).

Eligibility criteria:
inclusion criteria: * patient or legal guardian, if permitted by local regulatory authorities, provides informed consent to participate in the study must be performed before any procedure's protocol related * age of ≥25 years old * performance score ≥70 in accordance with the karnofsky performance score (kps), * life expectancy period of at least 3 months on the screening day, * have measurable disease according to response evaluation criteria in solid tumors version 1.1 (recist v1.1) * subject (or his/her partner) of childbearing potential willingness to use acceptable forms of contraception * adequate blood, liver, renal and urine parameters * phosphate levels within normal range * hiv, hcv (hepatitis c virus) and hbv negative (hepatitis b virus), * adequate cardiac function inclusion criteria specific for parts: part 1 * patients with histologically confirmed advanced gastric cancer, bladder cancer, squamous lung cancer or non-small cell lung cancer with squamous immunophenotype, cholangiocarcinoma, sarcoma or endometrial cancer, be refractory to prior therapies and without effective further treatment options. part 2 and 3 * patients with histologically confirmed advanced gastric cancer, bladder cancer, squamous lung cancer or non-small cell lung cancer with squamous immunophenotype, be refractory to prior therapies and without effective further treatment options. * subject's archival formalin-fixed paraffin-embedded (ffpe) tumour sample available for molecular alteration diagnostics, and/or a possibility to collect a new biopsy. * present molecular alteration within fgfr 1, 2 or 3 exclusion criteria: * any other current malignancy or malignancy diagnosed within the past five (5) years. * active brain metastases or leptomeningeal metastases. * concurrent anticancer treatment within 28 days before the start of trial treatment; major surgery within 28 days before the start of trial treatment); use of blood transfusion within 7 days before the start of trial treatment, * prior therapy with an agent directed to another fgfr inhibitor, * pregnancy and/or breastfeeding, * phosphate levels above the upper limit of normal, * ectopic calcification/mineralization, * endocrine alteration related to calcium/phosphate homeostasis e.g. parathyroid disorders, history of parathyroidectomy, * concomitant therapies increasing calcium/phosphate serum levels, * inability to take oral medicines, * corneal disorder and/or keratopathy, * persisting toxicity related to prior therapy grade \> 1 ctcae v5.0, except polyneuropathy and alopecia, * clinically significant (i.e., active) cardiovascular disease. history of abdominal fistula, bowel obstruction (grade iv), gastrointestinal perforation, intra-abdominal abscess within 6 months of enrollment. other significant diseases, which, in the opinion of the investigator, might impair the subject's tolerance of trial treatment. * receipt of any organ transplantation including allogeneic stem-cell transplantation. exclusion criteria specific for parts: part 2 and 3 * no ffpe tumour sample available to conduct fgfr alteration eligibility tests and no biopsy option.

Keywords: fgfr kinase inhibitor advanced solid tumors carcinoma neoplasms gastric cancer bladder cancer squamous non-small cell lung cancer squamous immunophenotype