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

Prior treatment

• 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,
• persisting toxicity related to prior therapy Grade \> 1 CTCAE v5.0, except polyneuropathy and alopecia,
• Receipt of any organ transplantation including allogeneic stem-cell transplantation.

Other illness

• Any other current malignancy or malignancy diagnosed within the past five (5) years.
• corneal disorder and/or keratopathy,
• 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.

Lab values

• endocrine alteration related to calcium/phosphate homeostasis e.g. parathyroid disorders, history of parathyroidectomy,
• concomitant therapies increasing calcium/phosphate serum levels,

Other

• Active brain metastases or leptomeningeal metastases.
• pregnancy and/or breastfeeding,
• phosphate levels above the upper limit of normal,
• ectopic calcification/mineralization,
• inability to take oral medicines,
• Part 2 and 3
• No FFPE tumour sample available to conduct FGFR alteration eligibility tests and no biopsy option.

• 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
• 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