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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 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 neuroendocrine tumors. The purpose of the phase 1b study to establish the maximum tolerated dose (MTD), and/or recommended phase 2 dose (RP2D). Preliminary efficacy and pharmacokinetic properties will be aslo evaluated.

Inclusion Criteria:

1. Histologically confirmed neuroendocrine tumors (G1, G2, G3).
2. Locally advanced or metastatic disease for which no standard therapy is judged appropriate by the investigator.
3. Male or non-pregnant, non-lactating female patients age ≥18 years.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.
5. Estimated life span ≥3 months.
6. At least one measurable lesion by RECIST 1.1.
7. Adequate hematologic and bone marrow functions.
8. Adequate renal and liver function.
9. Adequate cardiac function.
10. Brain metastases with clinically controlled neurologic symptoms.
11. 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.
12. Ability to understand and willingness to sign a written informed consent form (the consent form must be signed by the patient prior to any study-specific procedures).
13. Willingness and ability to comply with study procedures and follow-up examination.

Exclusion Criteria:

1. Neuroendocrine carcinoma (NEC).
2. Received chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, or any investigational therapy within 28 days prior to the first dose of study drug; received TKIs within 5 x half-time.
3. Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not recover to < Grade 2.
4. Known bleeding diathesis/disorder.
5. Recent history of non-chemotherapy induced thrombocytopenia associated bleeding within 1 year prior to first dose of study drug.
6. Have active immune thrombocytopenic purpura (ITP), active autoimmune hemolytic anemia (AIHA), or a history of being refractory to platelet transfusions (within 1 year prior to the first dose of study drug).
7. Serious gastrointestinal bleeding within 3 months.
8. Use of therapeutic doses of anti-coagulants is excluded, along with anti-platelet agents; low-dose anticoagulation medications that are used to maintain the patency of a central intravenous catheter are permitted.
9. Failure to recover adequately, as judged by the investigator, from prior surgical procedures. Patients who have had major surgery within 28 days from study entry, and patients who have had minor surgery within 14 days of study entry.
10. Unstable angina, myocardial infarction, or a coronary revascularization procedure within 180 days of study entry.
11. Uncontrolled concurrent illness including, but not limited to: serious uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with the study requirements.
12. Prior treatment with Bcl-2/Bcl-xL inhibitors.
13. Any other condition or circumstance of that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.