Treatment of recurrent or refractory neuroblastoma in children with APG-115 and APG-2575

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

This study is testing a new treatment using two drugs, APG-115 and APG-2575, to see if they can help children with hard-to-treat neuroblastoma or solid tumors feel better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 12 Years to 18 Years
• Sex: All
• Sponsor: Ascentage Pharma Group Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 3 sites (Guangzhou, Guangdong and 2 other locations)
• Trial ID: NCT05701306 on ClinicalTrials.gov

What this trial studies

This Phase I trial evaluates the safety and initial efficacy of APG-115 alone and in combination with APG-2575 in children with recurrent or refractory neuroblastoma or solid tumors. The study consists of two parts: the first part focuses on dose escalation of APG-115 to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). The second part involves dose escalation of APG-2575 in combination with APG-115 to establish the MTD and RP2D for the combination therapy.

Who should consider this trial

Good fit: Ideal candidates include children with recurrent or refractory neuroblastoma or solid tumors who meet specific health criteria.

Not a fit: Patients with non-recurrent or non-refractory tumors or those with severe health conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for children with difficult-to-treat neuroblastoma or solid tumors.

How similar studies have performed: Other studies have shown promise with similar approaches in treating pediatric solid tumors, indicating potential for success.

Eligibility criteria

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.

Where this trial is running

Guangzhou, Guangdong and 2 other locations

• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)
• Tongji Hospital, Huazhong University of Science and Technology (HUST) — Wuhan, Hubei, China (Recruiting)
• Tianjin Medical University Cancer Institute & Hospital — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Principal investigator: Yizhuo Zhang — Sun Yat-sen University
• Study coordinator: Yifan Zhai, MD,PHD

Conditions Neuroblastoma; Solid Tumor; APG-115