A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics, and Antitumor Activity of JSKN022 in Subjects With Advanced Malignant Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 225
- 试验地点
- 1
- 主要终点
- Frequency and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), etc (Safety and tolerability of JSKN-022).
研究概览
简要总结
The goal of this clinical trial is to learn if drug JSKN022 is safe to treat patients with advanced malignant solid tumors. It will also learn about the pharmacokinetic/ pharmacodynamic profiles and preliminary antitumor activity of drug JSKN022.
详细描述
This is a Phase I, open-label, multi-center, first-in-human (FIH) clinical trial designed to evaluate the safety, tolerability, pharmacokinetic (PK)/pharmacodynamic (PD) profiles, and antitumor activity of JSKN022 in patients with advanced malignant solid tumors.
Patients to be enrolled are with advanced unresectable or metastatic epithelial-derived malignant solid tumors confirmed by histology and/or cytology, who have failed previous standard treatment (disease progression), or be intolerant to standard treatment, or have no access to standard treatment.
The primary objective of the study is to evaluate the safety and tolerability of JSKN022 in patients with advanced malignant solid tumors and to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of JSKN022.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntarily participate and sign the informed consent form.
- •Age ≥ 18 years old, male or female.
- •Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or
- •Expected survival ≥ 3 months.
- •Histologically or cytologically confirmed malignant solid tumors confirmed by histology and/or cytology, who have failed previous standard treatment (disease progression), are intolerant to standard treatment, or have no access to standard treatment.
- •At least one measurable lesion at baseline according to RECIST 1.1 criteria.
- •Adequate organ function.
- •Agree to provide Recently archived or fresh tumor tissue samples.
- •Female subjects of childbearing potential or male subjects whose partners are of childbearing potential agree to use effective contraceptive measures.
- •Female subjects of childbearing potential must have a negative serum/urine pregnancy test within 7 days before the first dose.
- •Be able and willing to comply with the visits, treatment plans, laboratory tests, and other study-related procedures specified in the study protocol.
- •Adequate washout period of previous therapy before the first dose.
排除标准
- •Complicated with other malignant tumors within 5 years before the first dose, except for tumor types that have achieved clinical cure through local treatment with extremely low recurrence risk or tumor types with disease-free survival ≥ 5 years after radical treatment and extremely low recurrence/metastasis risk.
- •History of brainstem, meningeal metastasis, spinal cord metastasis or compression, or carcinomatous meningitis; presence of active brain metastasis.
- •Screening imaging shows tumor invasion, compression, or occurrence in surrounding important organs or risk of esophagotracheal fistula or esophagopleural fistula, except those judged by the investigator and medical monitor to not affect the patient's enrollment and administration.
- •Presence of clinically severe respiratory impairment caused by pulmonary disease complications.
- •Presence of the risk factors related to interstitial lung disease (ILD) or non-infectious pneumonia:
- •Presence of cardiovascular and cerebrovascular diseases or cardiovascular and cerebrovascular risk factors.
- •Gastrointestinal abnormalities with obvious clinical manifestations.
- •Active autoimmune diseases requiring systemic treatment within the past two years.
- •Significant serous effusion.
- •Uncontrolled infection.
- •Require regular glucocorticoid or immunosuppressive therapy.
- •Received live vaccines within 28 days before the first dose, or plan to receive live vaccines during the study period.
- •Prior treatment with antibody-drug conjugates containing topoisomerase I inhibitors.
- •Previous occurrence of grade ≥ 3 immune-related adverse events during immunotherapy.
- •Toxicity of previous anti-tumor treatment has not fully or partially recovered.
- •Known allergy to any component of the study drug, or history of severe allergic reactions to other antibody drugs.
- •Pregnant and/or lactating women, or planning to become pregnant during the study period.
- •Known history of mental illness, substance abuse, alcoholism, etc., or other situations that the investigator deems may affect the safety or compliance of the study drug treatment.
- •Local or systemic diseases caused by non-malignant tumors, or diseases or symptoms secondary to tumors, which may lead to high medical risks and/or uncertainty in survival assessment, such as tumor-related leukemia reaction (white blood cell count > 20×10⁹/L), cachexia manifestations, etc.
- •Any other previous or current diseases, treatments, or laboratory test abnormalities that the investigator deems may confuse the study results, affect the patient's full participation in the study, or participation in the study may not be in the best interest of the patient.
研究组 & 干预措施
Dose escalation cohorts 1
干预措施: JSKN022 (Drug)
Dose escalation cohort 2
干预措施: JSKN022 (Drug)
Dose escalation cohort 3
干预措施: JSKN022 (Drug)
Dose escalation cohort 4
干预措施: JSKN022 (Drug)
Dose escalation cohort 5
干预措施: JSKN022 (Drug)
Dose escalation cohort 6
干预措施: JSKN022 (Drug)
Dose escalation cohort 7
干预措施: JSKN022 (Drug)
Dose escalation cohort 8
干预措施: JSKN022 (Drug)
Dose optimization cohort in selected tumor type 1
干预措施: JSKN022 (Drug)
Dose optimization cohort in selected tumor type 2
干预措施: JSKN022 (Drug)
Dose optimization cohort 3 - other advanced epithelial malignant tumors cohort
干预措施: JSKN022 (Drug)
结局指标
主要结局
Frequency and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), etc (Safety and tolerability of JSKN-022).
时间窗: From the first dose to 30 days after the last dose or until initiation of new anti-tumor treatment, whichever comes first.
Frequency and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), etc.; abnormalities in physical examinations, laboratory tests, electrocardiograms, and other safety assessments.
Incidence of dose-limiting toxicity (DLT) in each dose group
时间窗: 21 days from the first dose
Maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of JSKN022.
时间窗: Up to 24 months
次要结局
- Objective response rate (ORR)(From the first study drug dose, until: disease progression per RECIST 1.1; initiation of new anti-tumor treatment; withdrawal of informed consent; death; loss to follow-up; or study termination, whichever comes first. Assessed at approximately 12 months.)
- Duration of response (DoR)(From the first study drug dose, until: disease progression per RECIST 1.1; initiation of new anti-tumor treatment; withdrawal of informed consent; death; loss to follow-up; or study termination, whichever comes first. Assessed up to 24 months.)
- Disease control rate (DCR)(From the first study drug dose, until: disease progression per RECIST 1.1; initiation of new anti-tumor treatment; withdrawal of informed consent; death; loss to follow-up; or study termination, whichever comes first. Assessed at approximately 12 months.)
- Clinical benefit rate (CBR)(From the first study drug dose, until: disease progression per RECIST 1.1; initiation of new anti-tumor treatment; withdrawal of informed consent; death; loss to follow-up; or study termination, whichever comes first. Assessed at approximately 12 months.)
- Incidence of anti-drug antibodies (ADA), antibody titers, and incidence of neutralizing antibodies (Nab, if applicable).(Up to 24 months)
- Maximum concentration (Cmax) of JSKN022(From the enrollment until the end of study. Assessed up to 24 months.)
- Progression-Free Survival (PFS)(From the first study drug dose, until: disease progression per RECIST 1.1; initiation of new anti-tumor treatment; withdrawal of informed consent; death; loss to follow-up; or study termination, whichever comes first. Assessed up to 24 months.)
- 6-Month and 12-Month Overall Survival Rates(From the first administration of the study drug until the death. Assessed up to 24 months.)
- Trough concentration (Ctrough) of JSKN022(From the enrollment until the end of study. Assessed up to 24 months.)
- Area under the concentration-time curve of JSKN022(From the enrollment until the end of study. Assessed up to 24 months.)
- Volume of distribution (V) of JSKN022(From the enrollment until the end of study. Assessed up to 24 months.)
- Time to maximum concentration (Tmax) of JSKN022(From the enrollment until the end of study. Assessed up to 24 months.)
- Elimination half-life (t1/2) of JSKN022(From the enrollment until the end of study. Assessed up to 24 months.)
- Clearance (CL) of JSKN022(From the enrollment until the end of study. Assessed up to 24 months.)