APG-2449 is a novel, orally active, multi-targeted tyrosine kinase inhibitor, which inhibits FAK, ALK, and ROS1 with nanomolar potencies. In preclinical studies, APG-2449 demonstrated potent antiproliferative activity in various cancer cell lines as a single agent. In combination treatment, APG-2449 enhanced anti-proliferative activities of several chemotherapeutic and targeted agents. It is indicated that APG-2449 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-2449 is intended for the treatment of patients with advanced solid tumors. Upon completion of the Phase 1 dose escalation study to establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and/or recommended phase 2 dose (RP2D), several phase Ib/II studies will be implemented accordingly.
- Added: May 10th, 2019.
- Last updated: May 10th, 2019.
Primary Outcome Measures
- Maximum Tolerated Dose (MTD) [ Time Frame: 28 days ]To determine the maximum tolerated dose (MTD) of APG-2449 in subjects with advanced solid tumors
- Recommended Phase 2 dose (RP2D) [ Time Frame: 28 days ]To determine the tentative recommended Phase 2 dose (RP2D) of APG-2449 in subjects with advanced solid tumors
Secondary Outcome Measures
- Maximum plasma concentration (Cmax) [ Time Frame: 28 days ]Maximum plasma concentration (Cmax) will be assessed on all participants with APG-2449 treatments
- Area under the plasma concentration versus time curve (AUC) [ Time Frame: 28 days ]Area under the plasma concentration versus time curve (AUC) will be assessed on all participants with APG-2449 treatments
- Phosphorylation of FAK protein [ Time Frame: 28 days ]Phosphorylation of FAK protein will be assessed in peripheral blood mononuclear cells on all participants with APG-2449 treatments
- Preliminary efficacy assessment: Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 [ Time Frame: 4 weeks ]To assess preliminary efficacy in subjects with solid tumors using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
- Histologically or cytologically confirmed advanced solid tumors that has relapsed from or is refractory to standard treatment, including NSCLC, malignant pleural mesothelioma, esophageal cancer, ovarian cancer, et al.
- ECOG Performance Status ≤ 1.
- Expectation of life ≥ 3 months.
- Adequate hematologic and bone marrow functions.
- Adequate renal and liver function.
- Normal cardiac function.
- Brain metastases with clinically controlled neurologic symptoms.
- Ability to understand and willingness to sign a written informed consent form.
- Willingness to provide tumor samples for testing FAK and p-FAK expression.
- Receiving concurrent anti-cancer therapy (chemotherapy, radiotherapy, immunotherapy, biologic therapy); or any investigational therapy within 28 days prior to the first dose of study drug.
- Receiving TKI therapy within 14 days prior to the first dose of study drug.
- Continuance of toxicities due to prior therapy that do not recover (CTCAE V5.0 grade> 1)
- Has difficulty in swallowing, absorbing barrier, or other diseases blocking APG-2449 ‘ taken.
- Obvious cardiovascular disease history.
- History of SAE due to prior TKI therapy.
- 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.
- Active symptomatic fungal, bacterial and/or viral infection including, but not limited to, active human immunodeficiency virus (HIV) or viral hepatitis (B or C).
- Any other condition or circumstance of that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.
- Receiving inhibitors or inducers of CYP3A4, CYP2C9 or CYP2C19 within 7 days prior to the first dose of study drug or during the study.
- Receiving substrates of CYP3A4 with narrow therapy window within 7 days prior to the first dose of study drug or during the study.
Source: the U.S. National Institutes of Health via ClinicalTrials.gov. Last updated: May 10th, 2019.
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