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

Primary Purpose

Neuroblastoma, Solid Tumor

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
APG-115
APG-2575
Sponsored by
Ascentage Pharma Group Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroblastoma focused on measuring Neuroblastoma, Solid Tumor, APG-115

Eligibility Criteria

12 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. Fresh or archived tumor tissue samples should be provided prior to treatment. If none of these specimens are available, inclusion may be made after consultation with the sponsor. 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. Exclusion Criteria: 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.

Sites / Locations

  • Sun Yat-sen University Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

APG-115 monotherapy in part1

APG-115 combined with APG-2575 in part2

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Full Information

First Posted
January 18, 2023
Last Updated
March 23, 2023
Sponsor
Ascentage Pharma Group Inc.
Collaborators
Suzhou Yasheng Pharmaceutical Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05701306
Brief Title
APG-115 Alone or in Combination With APG-2575 in Children With Recurrent or Refractory Neuroblastoma or Solid Tumors
Official Title
A Phase I Clinical Study of APG-115 Alone or in Combination With APG-2575 in Children With Recurrent or Refractory Neuroblastoma or Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 23, 2023 (Actual)
Primary Completion Date
June 1, 2026 (Anticipated)
Study Completion Date
December 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ascentage Pharma Group Inc.
Collaborators
Suzhou Yasheng Pharmaceutical Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.
Detailed Description
Part 1: Dose escalation and expansion of APG-115 monotherapy in pediatric neuroblastoma or solid tumors to determine MTD and recommended phase 2 dose, RP2D. Part 2: Dose escalation of APG-2575 to determine the MTD and RP2D combined with APG-115 at the dose level determined in part 1 in pediatric neuroblastoma or solid tumor, and extend the RP2D level of the combination therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma, Solid Tumor
Keywords
Neuroblastoma, Solid Tumor, APG-115

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
APG-115 monotherapy in part1
Arm Type
Experimental
Arm Description
Multiple dose cohorts, to determine the RP2D of APG-115.
Arm Title
APG-115 combined with APG-2575 in part2
Arm Type
Experimental
Arm Description
Multiple dose cohorts of APG-2575, to determine the RP2D of APG-2575 combined with APG-115.
Intervention Type
Drug
Intervention Name(s)
APG-115
Intervention Description
Orally once every other day(QOD) for 2 weeks and suspended for 1 week, 21 days as a cycle.
Intervention Type
Drug
Intervention Name(s)
APG-2575
Intervention Description
Orally once a day (QD) for 21 days, 21 days as a cycle.
Primary Outcome Measure Information:
Title
Dose Limiting Toxicity (Phase I)
Description
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.
Time Frame
Up to 21 days
Title
Treatment-Emergent Adverse Events per NCI-CTCAE version 5.0
Description
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.
Time Frame
Up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Fresh or archived tumor tissue samples should be provided prior to treatment. If none of these specimens are available, inclusion may be made after consultation with the sponsor. 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. Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yifan Zhai, MD,PHD
Phone
+86-20-28068501
Email
Yzhai@ascentage.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yan Yu
Email
Yan.Yu@ascentage.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yizhuo Zhang
Organizational Affiliation
Sun Yat-sen University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sun Yat-sen University Cancer Center
City
Guangzhou
State/Province
Guangdong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yizhuo Zhang, Ph.D
First Name & Middle Initial & Last Name & Degree
Yizhuo Zhang, Ph.D

12. IPD Sharing Statement

Learn more about this trial

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

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