APG-115 Alone or in Combination With APG-2575 in Children With Recurrent or Refractory Neuroblastoma or Solid Tumors

NCT05701306 | Recruiting Phase 1

• 1 other identifier: APG115XC103
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 3

Brief Summary

An open, non-randomized Phase I trial of dose-escalation and cohorts expansion to evaluate the safety, pharmacokinetic profile and initial efficacy of APG-115 alone or in combination with APG-2575 in the treatment of recurrent or refractory pediatric neuroblastoma or solid tumors.

Conditions

Neuroblastoma; Solid Tumor

Keywords

Neuroblastoma; Solid Tumor; APG-115

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity (Phase I)

  DLT will be defined based on the rate of drug-related grade 3-5 adverse events experienced within the first 3 weeks of study treatment. These will be assessed via CTCAE version 5.0.

  Up to 21 days

• Treatment-Emergent Adverse Events per NCI-CTCAE version 5.0

  Number of patients with adverse event; Number of patients with abnormal vital signs, abnorma physical examination, laboratory abnormalities, and abnormal 12-lead ECG in monotherapy of APG-115 and combined with APG-2575.

  Up to 12 months

Study Arms (2)

APG-115 monotherapy in part1

EXPERIMENTAL

Multiple dose cohorts, to determine the RP2D of APG-115.

Drug: APG-115

APG-115 combined with APG-2575 in part2

EXPERIMENTAL

Multiple dose cohorts of APG-2575, to determine the RP2D of APG-2575 combined with APG-115.

Drug: APG-115; Drug: APG-2575

Interventions

APG-115 DRUG

Orally once every other day(QOD) for 2 weeks and suspended for 1 week, 21 days as a cycle.

APG-115 combined with APG-2575 in part2; APG-115 monotherapy in part1

APG-2575 DRUG

Orally once a day (QD) for 21 days, 21 days as a cycle.

APG-115 combined with APG-2575 in part2

Eligibility Criteria

• Age: 12 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Recurrent or refractory neuroblastoma or solid tumor.
• Physical state score ≥ 50.
• Expected survival ≥ 3 months.
• There are target lesions (neuroblastoma) or measurable lesions (other solid tumors).
• Have adequate organ function.
• Fertile women (≥14 years of age or having menarche) must have a negative serum pregnancy test at the time of the screening visit and must not be breastfeeding or planning to become pregnant during the study period.
• A potentially fertile male subject (who has spermatoses) or female subject (ibid.) must agree to use effective contraception during the trial period and for 3 months after the trial ends (or is prematurely discontinued).
• Informed consent must be obtained before carrying out any study procedure specified in the test. For child subjects, the consent of the subject and one of the parent/legal guardian must be obtained.
• The ability to swallow research drugs.

You may not qualify if:

• Systemic antitumor therapy, including biotherapy, chemotherapy, surgery, radiotherapy, immunotherapy, and other investigational drug therapy (other than placebo), was received within 21 days prior to the first treatment with the study drug.
• Small-molecule targeted drug therapy was administered 14 days before the first treatment of the study drug or within a known five-half-life period, whichever is shorter.
• Patients who, according to the investigators' judgment, did not recover sufficiently after surgical treatment. Patients who underwent major surgery within 28 days before receiving the study drug for the first time.
• Adverse events due to previous antitumor therapy (except grade 2 peripheral neurotoxicity and alopecia that the investigators judged to be of no safety risk) have not recovered (severity higher than grade 1 according to CTCAE version 5.0).
• Patients with active brain tumors or brain metastases.
• Active gastrointestinal diseases (e.g. Crohn's disease, ulcerative colitis, or short bowel syndrome) or other malabsorption syndromes that may affect drug absorption.
• A known hemorrhagic predisposition/disease, such as a history of non-chemotherapy-induced thrombocytopenic bleeding within 1 year before first receiving the study drug; Have active immune thrombocytopenic purpura (ITP), active autoimmune hemolytic anemia (AIHA), or a history of platelet transfusion failure (within 1 year before first receiving the study drug); Severe gastrointestinal bleeding occurred within 3 months.
• Clinically significant cardiovascular disease, cardiomyopathy, myocardial infarction or history within 6 months prior to administration.
• Symptomatic active fungal, bacterial, and/or viral infections requiring systemic treatment.
• Unexplained fever \> 38.5℃ within 2 weeks prior to initial administration (subjects with tumor-related fever, as determined by the investigator, could be enrolled).
• Received MDM2 inhibitors or BCL-2 inhibitors.
• Any other circumstances or conditions that the investigator considers the patient inappropriate for participation in the study.

Sponsors & Collaborators

• Ascentage Pharma Group Inc.: lead
• Suzhou Yasheng Pharmaceutical Co., Ltd.: collaborator

Study Sites (3)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

RECRUITING

Tongji Hospital, Huazhong University of Science and Technology (HUST)

Wuhan, Hubei, 430030, China

RECRUITING

Tianjin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, 300060, China

RECRUITING

MeSH Terms

Conditions

Neuroblastoma

Interventions

Lisaftoclax

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Yizhuo Zhang

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yifan Zhai, MD,PHD

CONTACT

+86-20-28068501; Yzhai@ascentage.com

Yan Yu

CONTACT

Yan.Yu@ascentage.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2023
• First Posted: January 27, 2023
• Study Start: February 28, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 25, 2025

Record last verified: 2025-02

Locations

CN (3)