APL-102 Capsule in Patients With Advanced Solid Tumors

This study will evaluate the safety and tolerability of APL-102 Capsule and characterize the pharmacokinetic (PK) profile in advanced solid tumor patients.

This study is an open, multicenter dose-escalation study to evaluate the safety and tolerance of APL-102 and obtain the relevant data of APL-102 in patients with advanced solid tumors. In the dose escalation stage, based on the incidence of dose limited toxicity (DLT) and adverse event (AE), explore and determine the maximum tolerated dose (MTD) and phase II recommended dose (RP2D). After RP2D and administration protocol are determined, an extended study will be conducted on 6-10 subjects to further evaluate the safety and antitumor activity of APL-102.

Eligibility Criteria:
Major Inclusion Criteria:

1. Male or female, age ≥ 18 and ≤ 75 years old.
2. Patients with unresectable or metastatic advanced solid tumors confirmed by histology or cytology, and after the failure of standard treatment, or cannot tolerate standard treatment, or have no standard treatment.
3. There were measurable lesions according to the efficacy evaluation criteria of solid tumors (RECIST version 1.1).
4. Eastern Cooperative Oncology Group(ECOG) performance status score is 0 to 1.
5. Life expectancy is more than 3 months after the first administration.
6. The organ function level must meet the following requirements:

   Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.0× upper limit of normal value (ULN) (patients with liver metastasis≤ 5 × ULN). Serum bilirubin ≤ 1.5×ULN (total bilirubin ≤ 3×ULN in patients with Gilbert syndrome). Absolute neutrophil count ≥ 1.5×10\^9/L. Platelet count ≥ 100×10\^9/ L. Hemoglobin ≥ 9 g / dL.
7. No other chemotherapy was received within four weeks before the first administration of the trial; All previous anti-tumor treatments, including targeted therapy and endocrine therapy, shall pass through at least five half-lives (or no more than 28 days) after receiving targeted therapy/endocrine therapy, and patient shall recover to the standard level specified in the test from the toxic reaction of the treatment.
8. For patients who have received radiotherapy for spine and/or peripheral limbs, they can only be enrolled after four weeks and two weeks before the first administration and should recover from the toxic reaction of treatment to the standard level specified in the study.
9. No major surgery was performed within four weeks before the first administration of APL-102., etc.

Major Exclusion Criteria:

1. Previous treatment with VEGF(vascular endothelial growth factor)/ VEGFR(vascular endothelial growth factor receptor) inhibitors (except bevacizumab for colorectal cancer).
2. In addition to the malignancies in the study, patients with systemic diseases leading to poor medical risk (such as uncontrollable infection in the active phase).
3. Life-threatening diseases, severe organ dysfunction, interference with the absorption or metabolism of APL-102, or other reasons that the researchers believe may endanger the safety of subjects or affect the integrity of research results.
4. Patients with a history of heart disease or potential risk of heart disease.
5. Patients with low circulatory function as defined by the New York Heart Association's (NYHA) functional criteria.
6. Patients with a definite diagnosis of chronic obstructive pulmonary disease, bronchial asthma or interstitial lung disease, or patients with forced expiratory volume in one second/ forced vital capacity (FEV1/FVC) ratio \< 80% in pulmonary function test.
7. Patients with decompensated cirrhosis or history of allogeneic bone marrow transplantation or organ transplantation.
8. Patients in repeated resting states during screening had mean systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or positive proteinuria (allowing antihypertensive agents to control blood pressure).
9. Patients requiring antiplatelet/anticoagulant therapy (including but not limited to aspirin or low molecular weight heparin sodium and warfarin).
10. Have a history of human immunodeficiency virus (HIV) infection or HIV antibody positive; or seropositive results consistent with active infection for hepatitis B virus (in case of only hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive, the examination of Hepatitis B (HBV) DNA copy number is needed) or hepatitis C virus.
11. Patients with the symptomatic primary brain tumor and/or secondary brain metastasis, uncontrollable antiepileptic drugs and requiring high-dose steroid treatment. Or cerebrovascular accident, transient ischemic attack, or intermittent claudication within six months before treatment.
12. Patients who need to be treated with drugs metabolized through Cytochrome P450 (CYP450) system, especially those who need to be treated with drugs metabolized through Cytochrome p450 3A4( CYP3A4).
13. Pregnant or lactating patients., etc.