NCT03529526Unknown1 期
An Open-Label, Multi-center, Dose-Escalation Phase I Study to Evaluate Safety, Tolerability, Pharmacokinetics and Immunogenicity of KN046 in Subjects With Advanced Solid Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Number of participants with dose limiting toxicity (DLT)
研究概览
简要总结
This is an open-label, multicenter, dose-escalation phase I study to assess the safety, tolerability and preliminary efficacy of KN046 in participants with all advanced solid tumors who are not able to have current standard anti-tumor therapies. The purpose of this study is to determine the maximum tolerated dose (MTD) or a biological effective dose (BED), to characterise the safety, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) and anti-tumor activity of KN046 as a single agent in adult participants with advanced solid tumors
研究设计
- 研究类型
- Interventional
- 干预模型
- Sequential
- 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
- •The subject must sign the informed consent form prior to the conduct of any study related procedures that are required during the screening period and are not considered part of standard of care.
- •Subjects must have histologic or cytologic confirmed Advanced solid tumors.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate organ function within 3 weeks prior to initial treatment.
- •Ability to comply with treatment, procedures and PK sample collection and the required study follow-up procedures.
- •Female patients and males with partners of childbearing potential should be using highly effective contraceptive measures (failure rate of less than 1% per year). Contraception should be continued for a period of 24 weeks after dosing has been completed.
- •Female patients must have a negative serum or urine pregnancy test
- •Female patients must not be breastfeeding.
排除标准
- •Subjects with brain metastases or leptomeningeal are excluded.
- •Concurrent enrollment in another clinical study, unless in a follow-up period or the study is an observational or non-interventional study.
- •Any kind of immunotherapy within 6 weeks of the first dose of study treatment.
- •Prior systemic cytotoxic chemotherapy, other anticancer drugs or growth factor within 28 days of the first dose of study treatment, or any investigational agents within 5 half-lives of the product.
- •Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the 1st dose of study treatment, or have an anticipated need for major surgery during the study.
- •Palliative radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the 1st dose of study treatment.
- •Prior treatment or with sequential monotherapy with anti-CTLA-4 and anti-PD-1/PD-L agents.
- •Patients who have received monotherapy with PD-L1 / PD-1, CTLA4 or other antibodies and had intolerable toxicity or required steroids to manage toxicity.
- •History of autoimmune or inflammatory disorders.
- •A current or prior use of immunosuppressive medication within 14 days of the 1st dose of study treatment.
- •Suspected latent tuberculosis infection, confirmed by Mantoux test and a chest x-ray.
- •Any unresolved toxicity NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
- •Any factors that increase the risk of QT (ECG interval measured from the onset of the QRS complex to the end of the T wave) interval corrected for heart rate (QTc) prolongation or risk of arrhythmic events (e.g., heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age) or mean QTc>470 msec.
- •Positive blood screen for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or human immunodeficiency virus 1/2 antibody (HIV 1/2 Ab).
- •History of severe allergic reactions to any unknown allergens or to parenteral administered recombinant protein product.
研究组 & 干预措施
KN046
Experimental
干预措施: KN046 (Drug)
结局指标
主要结局
Number of participants with dose limiting toxicity (DLT)
时间窗: During the first cycle (4 weeks) of treatment.
An DLT is defined as a ≥Grade 3 drug-related adverse event occurring within the first cycle (28 days) of dosing (excluding tumor flare causing local pain at sites of known or suspected tumor, localized rash, or a transient ≤Grade 3 infusion reaction) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
次要结局
- Number of participants with adverse events (AEs)(From the time of informed consent signed through 90 days after the last dose of KN046，up to 2 years.)
- Objective response rate (ORR)(From first dose of KN046 through 90 days after last dose of KN046, up to 2 years.)
- Duration of response (DoR)(up to 2 years.)
- Progression-free survival (PFS)(From first dose of KN046 through 90 days after last dose of KN046, up to 2 years.)
- Clinical benefit rate (CBR)(From first dose of KN046 through 90 days after last dose of KN046, up to 2 years.)
- Area under the curve (AUC) of KN046(From first dose of KN046 through 90 days after last dose of KN046, up to 9 months.)
- Maximum observed concentration (Cmax) of KN046(From first dose of KN046 through 90 days after last dose of KN046, up to 9 months.)
- Minimum observed plasma concentration (Ctrough) of KN046 at steady state(From first dose of KN046 through 90 days after last dose of KN046, up to 9 months.)
- Number of subjects who develop detectable anti-drug antibodies (ADAs)(Assessed before KN046 infusion in Cycle 1, 2, 3, 4, 5, 6 and at the mandatory Safety Follow-up Visit, maxium up to 2 years.)
- Number of subjects who develop detectable neutralizing ADA (NADA)(Assessed before KN046 infusion in Cycle 1, 2, 3, 4, 5, 6 and at the mandatory Safety Follow-up Visit, maxium up to 2 years.)
研究者
研究点 (1)
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