Advanced Pancreatic Cancer
Conditions
Keywords
IAP inhibitor, APG-1387, Pancreatic cancer, Inhibitor of apoptosis
Brief summary
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.
Detailed description
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.
Interventions
APG1387 will be administered IV days 1， 8, 15 and 22 of a 28 day cycle.
DRUGGemcitabine
Gemcitabine 1000 mg/m\^2 will be administered IV days 1, 8, and 15 of a 28 day cycle.
DRUGNab paclitaxel
Nab-Paclitaxel 125mg/m\^2 will be administered IV days 1, 8, and 15 of a 28 day cycle.
Sponsors
Ascentage Pharma Group Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects must be ≥18 years of age at time of informed consent 2. Able to comply with the study protocol, in the investigator's judgment 3. Expected survival ≥ 3 months 4. Histology or cytology confirmed as advanced pancreatic adenocarcinoma, and: * Standard treatment failed or intolerant to standard treatment(Phase Ib); * First line standard treatment failed (Phase II). 5. ECOG 0-1; 6. Adequate organ function. 7. Subjects must have at least one measurable lesion evaluated by Computed Tomography (CT) scan on RECIST ver.1.1 at pre-treatment
Exclusion criteria
1. Has had chemotherapy, radiation, target or other antitumor therapy within 14 days prior to the first dose of study drug. 2. Has received an investigational agent or used an investigational device within 28 days of the first dose of study drug. 3. Has received a therapy with TNFα within 28 days of the first dose of study drug. 4. Known active central nervous system involvement. 5. Has received IAP-inhibitor before. 6. Has had major surgery within 28 days of dosing of investigational agent, or minor surgery within 14 days. 7. Patients with clinically evident Hepatitis B surface antigen (HBs) positive, Hepatitis C virus (HCV) antibody positive, Human Immunodeficiency Virus (HIV) antibody positive. 8. Pregnant or breastfeeding (lactating) women. 9. Other situations that investigator think not suit for study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicities (DLT) of combination therapy (Applicable for: phase Ib stage ). | 28 days. | 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. |
| Overall Response Rate (Applicable for: phase II stage) . | Up to 2 years. | Evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to 2 years. | From date of treatment start until the date of death due to any cause. |
| Maximum plasma concentration (Cmax) | 28 days. | Cmax of APG-1387 and Nab-Paclitaxel will be assessed in the patients in this study. |
| Progression Free Survival (PFS) | Up to 2 years. | From date of treatment start until the date of progression or the date of death due to any cause. |
| Adverse events | Up to 2 years. | Adverse events (AE) and serious adverse events (SAE) will be graded according to NCI CTCAE Version 5.0. |
| Area under the plasma concentration versus time curve (AUC) | 28 days. | AUC of APG-1387 and Nab-Paclitaxel will be assessed in the patients in this study. |
| Duration of Response (DOR) | Up to 2 years. | From date of response until the date of progression. |
Countries
China
Outcome results
None listed