Safety, Tolerability and Pharmacokinetics of Oral CPL304110, in Adult Subjects With Advanced Solid Malignancies

A Phase I, Open-label, Multicentre, Dose Escalation Study to Assess Safety, Tolerability and Pharmacokinetics of Oral CPL304110, in Adult Subjects With Advanced Solid Malignancies

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).

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.