A Phase Ib-ⅡClinical Study of APG-115 Alone or in Combination With APG-2575 in Recurrent or Refractory Neuroblastoma or Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 5
- 主要终点
- Dose Limiting Toxicity (Phase I)
研究概览
简要总结
An open, non-randomized Phase Ib-II 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 neuroblastoma or solid tumors.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥5 years for APG-115 monotherapy; age ≥12 years for APG-115 + APG-2575 combination.
- •Relapsed or refractory neuroblastoma or solid tumors with no available or suitable standard therapy.
- •Physical state score ≥
- •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.
排除标准
- •Received biological therapy, chemotherapy, or other investigational drugs within 21 days prior to dosing.
- •Received radiotherapy, minor surgery/minimally-invasive surgery; small-molecule targeted agents, short-half-life chemotherapeutic agents, or traditional Chinese medicines with anti-tumor indications within 14 days prior to study drug administration (or within 5 half-lives, whichever is shorter).
- •Patients who, according to the investigators' judgment, did not recover sufficiently after surgical treatment. Patients who underwent major surgery within 21 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.
研究组 & 干预措施
APG-115 monotherapy in part1
Multiple dose cohorts, to determine the RP2D of APG-115.
干预措施: APG-115 (Drug)
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.
干预措施: APG-115 (Drug)
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.
干预措施: APG-2575 (Drug)
结局指标
主要结局
Dose Limiting Toxicity (Phase I)
时间窗: 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.
Treatment-Emergent Adverse Events per NCI-CTCAE version 5.0
时间窗: 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.
次要结局
未报告次要终点