APG-1387 in Patients With Advanced Solid Tumors or Hematologic Malignancies

Inclusion criteria

• Histologically or cytologically confirmed solid tumor or hematological malignancies
• Life expectancy ≥ 3 months
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
• Corrected QT interval (QTc) ≤ 450 ms in males, and ≤ 470 ms in females
• Adequate hematologic function
• International normalized ratio (INR), prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤1.5 x upper limit of normal (ULN)
• Adequate renal and liver function
• Willingness to use contraception
• Ability to understand and willingness to sign a written informed consent form
• Willingness and ability to comply with study procedures and follow-up examination
• Have provided tissue for biomarker analysis from a newly or recently-obtained biopsy of a tumor lesion not previously irradiated

Exclusion criteria

• Received chemotherapy within 21 days (42 days for nitrosoureas or mitomycin C) prior to entering the study
• Received hormonal, biologic (< 2 half-lives), small molecule targeted therapies or other anti-cancer therapy within 21 days of study entry
• Radiation or surgery within 14 days of study entry, thoracic radiation within 28 days of study entry
• Has known active central nervous (CNS) metastases and/or carcinomatous meningitis. Patients who have received prior radiotherapy for previous brain metastasis must have discontinued steroids for 14 days prior to study entry and be clinically stable
• Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not recover to ≤ Grade 1 except alopecia
• Requirement for corticosteroid treatment, with the exception of megestrol, local use of steroid
• Use of therapeutic anticoagulants
• International normalized ratio (INR) or activated partial thromboplastin time (APTT) ≥ 1.5 x ULN
• Concurrent treatment with an investigational agent or device within 28 days prior to the first dose of therapy
• Unstable angina, myocardial infarction, or a coronary revascularization procedure within 180 days of study entry
• Neurologic instability per clinical evaluation due to tumor involvement of the central nervous system (CNS)
• History of Bell's palsy
• Active rheumatoid arthritis (RA), active inflammatory bowel disease, chronic infections, or any other disease or condition associated with chronic inflammation
• Active infection requiring systemic antibiotic/ antifungal medication
• Known or suspected Wilson's Disease
• Prior treatment with IAP inhibitors
• History of hypersensitivity to paclitaxel, or any therapeutic antibody
• Has an active autoimmune disease, or a documented history of autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents
• Is on chronic systemic steroid therapy
• Has received a live vaccine within 30 days prior to first dose
• Has had an allogeneic tissue/solid organ transplant, prior stem cell or bone marrow transplant