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

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ClinicalTrials.gov Identifier: NCT05701306
Recruitment Status : Recruiting
First Posted : January 27, 2023
Last Update Posted : March 27, 2023
Suzhou Yasheng Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):
Ascentage Pharma Group Inc.

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.

Condition or disease Intervention/treatment Phase
Neuroblastoma Solid Tumor Drug: APG-115 Drug: APG-2575 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 23, 2023
Estimated Primary Completion Date : June 1, 2026
Estimated Study Completion Date : December 31, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Neuroblastoma

Arm Intervention/treatment
Experimental: APG-115 monotherapy in part1
Multiple dose cohorts, to determine the RP2D of APG-115.
Drug: APG-115
Orally once every other day(QOD) for 2 weeks and suspended for 1 week, 21 days as a cycle.

Experimental: APG-115 combined with APG-2575 in part2
Multiple dose cohorts of APG-2575, to determine the RP2D of APG-2575 combined with APG-115.
Drug: APG-115
Orally once every other day(QOD) for 2 weeks and suspended for 1 week, 21 days as a cycle.

Drug: APG-2575
Orally once a day (QD) for 21 days, 21 days as a cycle.

Primary Outcome Measures :
  1. Dose Limiting Toxicity (Phase I) [ Time Frame: Up to 21 days ]
    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.

  2. Treatment-Emergent Adverse Events per NCI-CTCAE version 5.0 [ Time Frame: Up to 12 months ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Recurrent or refractory neuroblastoma or solid tumor.
  2. Physical state score ≥ 50.
  3. Expected survival ≥ 3 months.
  4. There are target lesions (neuroblastoma) or measurable lesions (other solid tumors).
  5. Have adequate organ function.
  6. 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.
  7. 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.
  8. 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).
  9. 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.
  10. The ability to swallow research drugs.

Exclusion Criteria:

  1. 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.
  2. 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.
  3. 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.
  4. 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).
  5. Patients with active brain tumors or brain metastases.
  6. Active gastrointestinal diseases (e.g. Crohn's disease, ulcerative colitis, or short bowel syndrome) or other malabsorption syndromes that may affect drug absorption.
  7. 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.
  8. Clinically significant cardiovascular disease, cardiomyopathy, myocardial infarction or history within 6 months prior to administration.
  9. Symptomatic active fungal, bacterial, and/or viral infections requiring systemic treatment.
  10. Unexplained fever > 38.5℃ within 2 weeks prior to initial administration (subjects with tumor-related fever, as determined by the investigator, could be enrolled).
  11. Received MDM2 inhibitors or BCL-2 inhibitors.
  12. Any other circumstances or conditions that the investigator considers the patient inappropriate for participation in the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05701306

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Contact: Yifan Zhai, MD,PHD +86-20-28068501 Yzhai@ascentage.com
Contact: Yan Yu Yan.Yu@ascentage.com

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China, Guangdong
Sun Yat-sen University Cancer Center Recruiting
Guangzhou, Guangdong, China
Contact: Yizhuo Zhang, Ph.D         
Principal Investigator: Yizhuo Zhang, Ph.D         
Sponsors and Collaborators
Ascentage Pharma Group Inc.
Suzhou Yasheng Pharmaceutical Co., Ltd.
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Principal Investigator: Yizhuo Zhang Sun Yat-sen University
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Responsible Party: Ascentage Pharma Group Inc.
ClinicalTrials.gov Identifier: NCT05701306    
Other Study ID Numbers: APG115XC103
First Posted: January 27, 2023    Key Record Dates
Last Update Posted: March 27, 2023
Last Verified: January 2023

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ascentage Pharma Group Inc.:
Solid Tumor
Additional relevant MeSH terms:
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Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue