A Study of IMP4297 in Patients With Advanced Solid Tumors

Inclusion criteria

• Signed Informed Consent Form
• 18 Years to 70 Years (including 18 and 75 years)
• Histologically or cytologically documented disease; incurable, advanced solid malignancy that has progressed on, or failed to respond to, at least one prior systemic therapy
• Eastern Cooperative Oncology Group performance status of 0 or 1
• In the dose expansion stage, patients with BRCA (breast carcinoma) mutation will be enrolled. Patients with breast cancer, ovarian cancer and prostate cancer are preferred.
• In the dose escalation phase, at least one assessable lesion according to the RECIST 1.1 standard; In the dose expansion phase, at least one measurable lesion according to RECIST 1.1.

Exclusion criteria

• Inadequate hematologic and organ function, defined by the following (hematologic parameters must be assessed ≥14 days after a prior treatment, if any):

• Absolute neutrophil count <1500 cells/µL
• Hemoglobin < 9 g/dL
• Total bilirubin > 1.5 × the upper limit of normal (ULN), with documented liver metastases total bilirubin > 3 × the ULN.
• Aspartate transaminase (AST) and/or alanine transaminase (ALT) > 2.5 × the ULN, with documented liver metastases AST and/or ALT levels > 5 × the ULN.
• Serum creatinine > 1.5 × the ULN, or creatinine clearance < 45 mL/min based on a documented 24-hour urine collection or Cockcroft-Gault calculation of glomerular filtration rate.
• International normalized ratio (INR) > 1.5 × the ULN or activated partial thromboplastin time (aPTT) > 1.5 × the ULN.

The INR applies only to patients who do not receive therapeutic anti-coagulation.

• Any anti-cancer therapy, including chemotherapy, hormonal therapy, biologic therapy, radiotherapy within 4 weeks prior to initiation of study treatment with the following exceptions:

• Hormonal therapy with gonadotropin-releasing hormone (GnRH) agonists for prostate cancer.
• Hormone-replacement therapy or oral contraceptives.
• Palliative radiation to bone metastases > 2 weeks prior to Day 1.
• Adverse events from prior anti-cancer therapy that have not resolved to NCI CTCAE Grade ≤ 1, except for alopecia.
• Prior therapies targeting PARP (poly-ADP ribose polymerase).
• Clinical significant active infection
• Known clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• Known human immunodeficiency virus infection
• New York Heart Association Class II or greater congestive heart failure; history of myocardial infarction or unstable angina within 6 months prior to Day 1; history of stroke or transient ischemic attack within 6 months prior to Day 1
• Active or untreated brain metastasis
• Pregnant (positive pregnancy test) or lactating women
• Male or female patients of child-producing potential unwilling to use double barrier contraception: condoms, sponge, foams, jellies, diaphragm or intrauterine device, contraceptives (oral, injectable or parenteral), implanon, or other avoidance of pregnancy measures during the study and for 90 days after the last day of treatment
• Inability to take oral medication, prior surgical procedures affecting absorption, or active peptic ulcer disease
• Inability to comply with study and follow-up procedures
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications.