A Study of Pelcitoclax (APG-1252) in Patients With Neuroendocrine Tumors

A Phase IB Study of Safety, Efficacy and Pharmacokinetic of Intravenously Administered Pelcitoclax (APG-1252) in Patients With Advanced Neuroendocrine Tumor

APG-1252 is a highly potent Bcl-2 family protein inhibitor, a promising drug candidate which shown high binding affinities to Bcl-2, Bcl-xL and Bcl-w. The preclinical studies have shown that APG-1252 alone achieves complete and persistent tumor regression in multiple tumor xenograft models with a twice weekly or weekly dose-schedule, including SCLC, colon, breast and ALL cancer xenografts; achieves strong synergy with the chemotherapeutic agents, indicating that APG-1252 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-1252 is intended for the treatment of patients with neuroendocrine tumors. The purpose of the phase 1b study to establish the maximum tolerated dose (MTD), and/or recommended phase 2 dose (RP2D). Preliminary efficacy and pharmacokinetic properties will be aslo evaluated.

Study Overview

• Status: Terminated
• Conditions: Neuroendocrine Tumors
• Intervention / Treatment: Drug: Pelcitoclax

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-sen University Cancer Center
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital of Sun Yat-sen University
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed neuroendocrine tumors (G1, G2, G3).
2. Locally advanced or metastatic disease for which no standard therapy is judged appropriate by the investigator.
3. Male or non-pregnant, non-lactating female patients age ≥18 years.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.
5. Estimated life span ≥3 months.
6. At least one measurable lesion by RECIST 1.1.
7. Adequate hematologic and bone marrow functions.
8. Adequate renal and liver function.
9. Adequate cardiac function.
10. Brain metastases with clinically controlled neurologic symptoms.
11. Willingness to use contraception by a method that is deemed effective by the investigator by both males and female patients of child bearing potential (postmenopausal women must have been amenorrheal for at least 12 months to be considered of non-childbearing potential) and their partners throughout the treatment period and for at least three months following the last dose of study drug.
12. Ability to understand and willingness to sign a written informed consent form (the consent form must be signed by the patient prior to any study-specific procedures).
13. Willingness and ability to comply with study procedures and follow-up examination.

Exclusion Criteria:

1. Neuroendocrine carcinoma (NEC).
2. Received chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, or any investigational therapy within 28 days prior to the first dose of study drug; received TKIs within 5 x half-time.
3. Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not recover to < Grade 2.
4. Known bleeding diathesis/disorder.
5. Recent history of non-chemotherapy induced thrombocytopenia associated bleeding within 1 year prior to first dose of study drug.
6. Have active immune thrombocytopenic purpura (ITP), active autoimmune hemolytic anemia (AIHA), or a history of being refractory to platelet transfusions (within 1 year prior to the first dose of study drug).
7. Serious gastrointestinal bleeding within 3 months.
8. Use of therapeutic doses of anti-coagulants is excluded, along with anti-platelet agents; low-dose anticoagulation medications that are used to maintain the patency of a central intravenous catheter are permitted.
9. 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.
10. Unstable angina, myocardial infarction, or a coronary revascularization procedure within 180 days of study entry.
11. Uncontrolled concurrent illness including, but not limited to: serious uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with the study requirements.
12. Prior treatment with Bcl-2/Bcl-xL inhibitors.
13. Any other condition or circumstance of that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: APG-1252	Drug: Pelcitoclax; Multiple dose cohorts, 30 minute IV infusion, once a week, 28 days as a cycle; Other Names: APG-1252

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD) determination	If ≥ 2/6 patients develop a DLT at any dose level, then the MTD will be assumed to have been exceeded. The dose level immediately below will then be expanded to 6 patients and, if no more than 1/6 patients develop DLT, then this dose will be declared the MTD.	28 days
Safety data	Incidence of adverse events (AEs)	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preliminary Efficacy	Objective response rate (ORR) assessed by RECIST 1.1	24 months
Preliminary Efficacy	Progress free survival (PFS) assessed by RECIST 1.1	24 months
Preliminary Efficacy	Disease control rate assessed (DCR) by RECIST 1.1	24 months
Pharmacokinetic	Peak plasma concentration (Cmax)	28 days

Collaborators and Investigators

• Sponsor: Ascentage Pharma Group Inc.
• Investigators: Principal Investigator: Xianjun Yu, Fudan University; Principal Investigator: Minhu Chen, M.D., PhD., First Affiliated Hospital, Sun Yat-Sen University; Principal Investigator: Jie Chen, M.D., PhD., Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2022
• Primary Completion (Actual): September 14, 2022
• Study Completion (Actual): September 14, 2022

Study Registration Dates

• First Submitted: May 11, 2021
• First Submitted That Met QC Criteria: May 14, 2021
• First Posted (Actual): May 19, 2021

Study Record Updates

• Last Update Posted (Actual): April 17, 2025
• Last Update Submitted That Met QC Criteria: April 15, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: BCL-2; BCL-xl
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors
• Other Study ID Numbers: APG1252EC101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No