Clinical trial NCT04643405: APG-1387 Plus Chemotherapy in Advanced Pancreatic Adenocarcinoma
Official title: An Open Label, Multiple Centers Phase Ib/II Study of APG-1387 Plus Chemotherapy in Advanced Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Pancreatic Cancer
Keywords: IAP inhibitor
APG-1387
Pancreatic cancer
Inhibitor of apoptosis
Lead sponsor: Ascentage Pharma Group Inc.
Sponsor class: INDUSTRY
First posted: 2020-11-25
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose Limiting Toxicities (DLT) of combination therapy (Applicable for: phase Ib stage ).
timeFrame: 28 days.
measure: Overall Response Rate (Applicable for: phase II stage) .
timeFrame: Up to 2 years.
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Up to 2 years.
measure: Duration of Response (DOR)
timeFrame: Up to 2 years.
measure: Overall Survival (OS)
timeFrame: Up to 2 years.
measure: Maximum plasma concentration (Cmax)
timeFrame: 28 days.
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: 28 days.
measure: Adverse events
timeFrame: Up to 2 years.
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Jiangsu Ascentage Pharma Co., Ltd.
name: Yifan Zhai, MD, PhD
role: STUDY_CHAIR
References: