A Phase I Study of the Safety, Pharmacokinetic and Pharmacodynamic Properties of Intravenously Administered APG-1252 in Patients With Small Cell Lung Cancer (SCLC) or Other Solid Tumors
APG-1252 is a highly potent Bcl-2 family protein inhibitor, a promising drug candidate which shown high binding affinities to Bcl-2, Bcl-xL and Bcl-w. The preclinical studies have shown that APG-1252 alone achieves complete and persistent tumor regression in multiple tumor xenograft models with a twice weekly or weekly dose-schedule, including SCLC, colon, breast and acute lymphocytic leukemia (ALL) cancer xenografts; achieves strong synergy with the chemotherapeutic agents, indicating that APG-1252 may have a broad therapeutic potential for the treatment of human cancer as a single agent and in combination with other classes of anticancer drugs. APG-1252 is intended for the treatment of patients with SCLC or other solid tumors. This is a multi-center, open-label, dose escalation Phase I study to determine the MTD and DLTs of intravenously administered APG-1252. After dose escalation to 240mg twice weekly, 2 dose cohorts two different dosing schedules including weekly and twice weekly will be assessed to evaluate for safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor efficacy. Treatment with APG-1252 will be administered to 30-60 patients at approximately 2 investigational sites in US.
• Histologically or cytologically confirmed small cell lung cancer (SCLC) or other solid tumors
• Male or non-pregnant, non-lactating female patients age ≥18 years
• Locally advanced or metastatic disease for which no standard therapy is judged appropriate by the investigator
• Eastern Cooperative Oncology Group (ECOG) Performance Status \< 2
• Adequate hematologic function as indicated by:
∙ Platelet count ≥ 100,000/mm˄3
‣ Hemoglobin ≥ 9.0g/dL Platelet count ≥ 100,000/mm˄3
‣ Absolute neutrophil count (ANC) ≥1000/µL
• Adequate renal and liver function as indicated by:
∙ Serum creatinine ≤ 1.5 x upper limit of normal (ULN); if serum creatinine is \>1.5 X ULN, creatinine clearance must be ≥ 50 mL/min
‣ Total bilirubin ≤1.5 x ULN; If Gilbert's Syndrome may have Bilirubin\> 1.5 x ULN
‣ Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤3 x ULN of institution's normal range; for patients with known liver metastases, AST and ALT may be ≤ 5 x ULN
‣ Coagulation: activated partial thromboplastin time (aPTT) and prothrombin time (PT)\<1.2 x the upper limit of normal
• Brain metastases with clinically controlled neurologic symptoms, defined as surgical excision and/or radiation therapy followed by 21 days of stable neurologic function and no evidence of CNS disease progression as determined by CT or MRI within 21 days prior to the first dose of study drug
• Willingness to use contraception by a method that is deemed effective by the investigator by both males and female patients of child bearing potential (postmenopausal women must have been amenorrheal for at least 12 months to be considered of non-childbearing potential) and their partners throughout the treatment period and for at least three months following the last dose of study drug
• Ability to understand and willingness to sign a written informed consent form
⁃ Willingness and ability to comply with study procedures and follow-up examination