This study is a two stage study consisting of a dose escalation phase Ib and a phase II study which include subjects with previously-treated, advanced pancreatic adenocarcinoma. Dose Limiting Toxicities (DLTs) and maximum tolerated dose (MTD) of APG1387 in combination with nab-paclitaxel and gemcitabine will be evaluated in the dose escalation phase Ib. Safety and efficacy of APG1387 plus gemcitabine and nab-paclitaxel will be evaluated in phase II.
The ability of tumor cells to evade apoptosis is currently a major problem in anti-tumor therapy. IAPs are an important class of apoptosis-regulating proteins. APG-1387, a potent bivalent SMAC mimetic, small molecule of IAP inhibitor, which could inhibit pancreatic cancer proliferation as monotherapy and in combination with chemotherapy through apoptosis pathway. It's an open label, multiple centers phase Ib/II Study. Safety and tolerability of APG1387 combined with nab-paclitaxel and gemcitabine will be evaluated in phase Ib in previously-treated, advanced pancreatic adenocarcinoma patients. Efficacy and tolerability will be evaluated in phase II study in first line standard treatment failed metastatic pancreatic adenocarcinoma patients.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
21
APG1387 will be administered IV days 1, 8, 15 and 22 of a 28 day cycle.
Gemcitabine 1000 mg/m\^2 will be administered IV days 1, 8, and 15 of a 28 day cycle.
Nab-Paclitaxel 125mg/m\^2 will be administered IV days 1, 8, and 15 of a 28 day cycle.
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, China
Dose Limiting Toxicities (DLT) of combination therapy (Applicable for: phase Ib stage ).
DLT will be graded according to NCI CTCAE Version 5.0. DLT will be defined as clinically significant drug-related adverse events during the cycle one.
Time frame: 28 days.
Overall Response Rate (Applicable for: phase II stage) .
Evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
Time frame: Up to 2 years.
Progression Free Survival (PFS)
From date of treatment start until the date of progression or the date of death due to any cause.
Time frame: Up to 2 years.
Duration of Response (DOR)
From date of response until the date of progression.
Time frame: Up to 2 years.
Overall Survival (OS)
From date of treatment start until the date of death due to any cause.
Time frame: Up to 2 years.
Maximum plasma concentration (Cmax)
Cmax of APG-1387 and Nab-Paclitaxel will be assessed in the patients in this study.
Time frame: 28 days.
Area under the plasma concentration versus time curve (AUC)
AUC of APG-1387 and Nab-Paclitaxel will be assessed in the patients in this study.
Time frame: 28 days.
Adverse events
Adverse events (AE) and serious adverse events (SAE) will be graded according to NCI CTCAE Version 5.0.
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Time frame: Up to 2 years.