A Phase 1 Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ASKG315 as a Single Agent and in Combination With Pembrolizumab in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Safety[DLTs、AEs、ECG]
研究概览
简要总结
The study is a Phase 1, open-label, multicenter, dose escalation study to evaluate the safety, tolerability, PK and PD of ASKG315 as a single agent (Part 1) and in combination with pembrolizumab (Part 2) in patients with advanced solid tumors.
详细描述
Each part of the study consists of 3 periods: screening (up to 28 days), treatment and follow-up. After an initial screening period, ASKG315 or ASKG315 combined with pembrolizumab will be administered once every 3 weeks by intravenous (IV) infusion. The Part 1 dose escalation consists of 6 planned escalation cohorts, with a starting dose of 3 mg. The Part 2 dose escalation consists of 4 planned escalation cohorts.
Part 2 of the study will begin enrolling after Part 1 has successfully and safely dosed all patients in the first two cohorts and followed these patients through the entire DLT period. The starting dose of Part 2 will be determined according to the safety and PK of ASKG315 in Part 1 of the study, but in no case will it exceed the highest dose already safely administered in Part 1 and confirmed as tolerable by the Safety Review Committee in Part 1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent form.
- •Male or female ≥ 18 years of age (at the time signed consent is obtained).
- •Histologically or cytologically confirmed advanced malignant solid tumor that is refractory to or intolerant of all standard therapy or for which no standard therapy is available.
- •Measurable disease, per RECIST v1.
- •ECOG Performance Status of ≤
- •Life expectancy of ≥3 months, in the opinion of the Investigator.
- •Adequate organ function defined.
- •Fertile patients must be willing to use effective contraceptive measures (hormonal or barrier methods or abstinence, etc.) starting with the Screening visit through 90 days + 5 drug half-lives after the last dose of study treatment.
- •Negative serum pregnancy test for female patients within 7 days prior to the first dose of the study drug or documentation of lack of childbearing potential.
- •Willing and able to participate in the trial and comply with all trial requirements.
排除标准
- •Patients who meet any of the following criteria are not allowed to be enrolled:
- •Received any other investigational drug for treatment that is not commercially available within 4 weeks prior to Cycle 1 Day
- •Received chemotherapy, radiotherapy, biotherapy, endocrine therapy, targeted therapy, immunotherapy, or any other anti-tumor treatments within 4 weeks prior to Cycle 1 Day
- •Had major organ surgery or significant trauma within 4 weeks prior to C1D1 or planning elective surgery during the study period.
- •Received systemic glucocorticoid or other immunosuppressant treatment within 14 days prior to C1D
- •Received immunomodulatory drugs, including but not limited to thymosin and interferon, within 14 days prior to C1D
- •Received a live attenuated vaccine within 4 weeks prior to C1D
- •Received IL-2 or IL-15 therapy within 12 weeks prior to C1D
- •History of hematologic stem cell transplant or solid organ transplant.
- •Adverse reactions to previous antitumor therapy have not recovered to CTCAE 5.0 grade ≤
- •Cerebral parenchymal metastasis or meningeal metastasis with clinical symptoms.
- •Have an active infection that currently requires intravenous anti-infection therapy.
- •A history of human immunodeficiency virus (HIV) infection with a CD4+ T-cell count of ≤350 cells/µL at screening. HIV positive patients must be receiving adequate treatment.
- •If serological evidence of chronic hepatitis B virus infection (HBV), viral load below the limit of quantification at screening.
- •If serological evidence of hepatitis C virus infection (HCV), should have completed curative antiviral treatment and have HCV viral load below the limit of quantification at screening.
- •Current clinically significant interstitial lung disease.
- •History of serious cardiovascular or cerebrovascular diseases.
- •Active or recurrent autoimmune diseases.
- •History of Grade ≥ 3 Immune-Related Adverse Events (irAE) or Grade ≥ 2 immunotherapy-associated myocarditis associated with treatment with an immune checkpoint inhibitor.
- •Grade ≥ 3 bleeding .
- •Symptomatic with uncontrolled ascites or pleural effusion.
- •History of a grade ≥ 3 allergic reaction to protein drugs.
- •Known to have alcohol or drug dependence.
结局指标
主要结局
Safety[DLTs、AEs、ECG]
时间窗: 21days
1. Incidence of dose limiting toxicities (DLTs) 2. Incidence of adverse events (AEs), laboratory abnormalities, and ECG abnormalities
次要结局
- Immunocyte(21days)
- Maximum plasma concentration (Cmax)(21days)
- Area under the concentration time curve (AUC)(21days)
- Cytokine(21days)