NCT04617314已完成1 期
A Phase I Study to Evaluate the Safety, Pharmacokinetics, and Effect of RC108-ADC For Injection in Subjects With c-Met Positive Advanced Malignant Solid Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 5
- 主要终点
- Number of participants with adverse events
研究概览
简要总结
This study will evaluate the safety, pharmacokinetics, and effect of RC108-ADC for injeciton in subjects with c-Met positive advanced malignant solid tumors.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary agreement to provide written informed consent.
- •Male or female, aged between 18 to 70 years.
- •Predicted survival for ≥ 12 weeks.
- •Diagnosed with histologically or cytologically confirmed locally advanced or metastatic solid tumors.
- •Measurable lesion according to RECIST 1.
- •c-Met positive as confirmed by the central laboratory. The subject is able to provide specimens from primary or metastatic lesions for c-Met tests.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or
- •Adequate organ function, evidenced by the following laboratory results within 7 days prior to the study treatment:
- •Cardiac ejection fraction ≥ 50%. Median QTc < 450 ms. Hemoglobin ≥ 9g/dL; Absolute neutrophil count ≥ 1.5×10^9 /L Platelets ≥ 100×10^9 /L; Total bilirubin ≤ 1.5× ULN; AST and ALT ≤ 2.5×ULN and ≤ 5 x ULN with hepatic metastasis; Serum creatinine ≤1.5×ULN.
- •All female subjects will be considered to be of child-bearing potential unless they are postmenopausal, or have been sterilized surgically. Female subjects of child-bearing potential must agree to use two forms of highly effective contraception. Male subjects and their female partner who are of child-bearing potential must agree to use two forms of highly effective contraception.
- •Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.
排除标准
- •Known hypersensitivity to the components of RC108-ADC.
- •Toxicity of previous anti-tumor treatment not recovered to CTCAE (v5.0) Grade 0-1 (with exception of Grade 2 alopecia).
- •Uncontrolled pericardial effusion or cardiac tamponade, or pleural or abdominal effusion with clinical symptoms.
- •History of receiving any anti-cancer drug/biologic treatment within 4 weeks prior to trial treatment.
- •History of major surgery within 4 weeks of planned start of trial treatment.
- •Has received a live virus vaccine within 4 weeks of planned start of trial treatment.
- •Currently known active infection with HIV or tuberculosis.
- •Diagnosed with HBsAg, HBcAb positive and HBV DNA copy positive, or HCVAb positive.
- •Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- •History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or cancers with a similar curative outcome as those mentioned above.
- •Known central nervous system metastases.
- •Uncontrolled hypertension, diabetes, pulmonary fibrosis, acute lung disease, Interstitial lung disease, or liver cirrhosis;
- •Pregnancy or lactation.
- •Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.
研究组 & 干预措施
RC108
Experimental
Participants will be allocated to one of the following dose groups: 0.1, 0.3, 0.9, 1.5, 2.0, 2.5, and 3.0mg/kg, and receive a treatment of RC108-ADC followed by 21 days of dose limited toxicity (DLT) observation period.
干预措施: RC108 (Drug)
结局指标
主要结局
Number of participants with adverse events
时间窗: From the day of ICF signment to 28 days after the day of the last treatment
Adverse events was assessed by investigator(s) according to NCI-CTCAE v4.03
Maximum Tolerated dose of RC108
时间窗: 21 days after first treatment.
The dose level in which \>= 2 out of 6 patients have dose-limiting toxicity (DLT). The MTD is defined as the previous dose level.
次要结局
- Objective Response Rate (ORR)(24 months)
- Progression Free Survival (PFS)(24 months)
- Pharmacokinetics (PK) parameter for total antibody (TAb): Maximum concentration (Cmax)(Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.)
- PK parameter for TAb: Time to maximum concentration (Tmax)(Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.)
- PK parameter for TAb: Area under the concentration-time curve (AUC)(Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.)
- PK parameter for TAb: Trough concentration (Ctrough)(Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.)
- PK parameter for TAb: Terminal or apparent terminal half-life (t1/2)(Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.)
- PK parameter for TAb: Systemic clearance (CL)(Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.)
- PK parameter for antibody-drug conjugate (ADC): Cmax(Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.)
- PK parameter for ADC: AUC(Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.)
- PK parameter for MMAE: Tmax(Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.)
- PK parameter for MMAE: AUC(Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.)
- PK parameter for MMAE: Ctrough(Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.)
- PK parameter for MMAE: t1/2(Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.)
- PK parameter for ADC: Tmax(Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.)
- PK parameter for ADC: Ctrough(Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.)
- PK parameter for ADC: t1/2(Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.)
- PK parameter for ADC: CL(Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.)
- PK parameter for Monomethyl Auristatin E (MMAE): Cmax(Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.)
- PK parameter for MMAE: CL(Dose 1 and Dose 3: pre-dose, 0.5 hour, 1 hour, 1.5 hours, 10 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours and 504 hours after start of infusion. Dose 2: pre-dose.)
- Immunogenicity assessment(Dose 1 to Dose 3: pre-dose, and 504 hours after start of infusion (Dose 3 only))
研究者
研究点 (5)
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