APG-1387 Plus Chemotherapy in Advanced Pancreatic Adenocarcinoma

NCT ID: NCT04643405

Last Updated: 2026-01-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-17
• Study Completion Date: 2024-12-10

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.

Conditions

Advanced Pancreatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

APG1387 in combination with Gemcitabine and Nab-Paclitaxel

Group Type: EXPERIMENTAL

APG-1387 for Injection

Intervention Type: DRUG

APG1387 will be administered IV days 1， 8, 15 and 22 of a 28 day cycle.

Gemcitabine

Intervention Type: DRUG

Gemcitabine 1000 mg/m\^2 will be administered IV days 1, 8, and 15 of a 28 day cycle.

Nab paclitaxel

Intervention Type: DRUG

Nab-Paclitaxel 125mg/m\^2 will be administered IV days 1, 8, and 15 of a 28 day cycle.

Interventions

APG-1387 for Injection

APG1387 will be administered IV days 1， 8, 15 and 22 of a 28 day cycle.

Intervention Type: DRUG

Gemcitabine

Gemcitabine 1000 mg/m\^2 will be administered IV days 1, 8, and 15 of a 28 day cycle.

Intervention Type: DRUG

Nab paclitaxel

Nab-Paclitaxel 125mg/m\^2 will be administered IV days 1, 8, and 15 of a 28 day cycle.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ascentage Pharma Group Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yifan Zhai, MD, PhD

Role: STUDY_CHAIR

Jiangsu Ascentage Pharma Co., Ltd.

Locations

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Countries

China

References

Shi S, Zhang J, Liu R, Gao S, Xu J, Wang W, Wei M, Li J, Liu C, Xu X, Pan W, Tian X, Men L, Wang H, Liang Z, Zhu M, Yang D, Zhai Y, Yu X. A phase 1 trial of APG-1387, an IAP antagonist, with nab-paclitaxel and gemcitabine in patients with refractory metastatic pancreatic cancer. Cell Rep Med. 2025 Oct 21;6(10):102364. doi: 10.1016/j.xcrm.2025.102364. Epub 2025 Sep 19.

Reference Type: DERIVED

PMID: 40975066 (View on PubMed)

Other Identifiers

APG1387PC101

Identifier Type: -

Identifier Source: org_study_id