A PhaseⅠStudy to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of FDA018-ADC in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- The maximum tolerated dose (MTD)
研究概览
简要总结
This is a Phase 1, open-label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics and efficacy of FDA018-ADC in patients with advanced/metastatic solid tumors.
详细描述
This is a first-in-human (FIH), Phase 1, open-label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of FDA018-ADC in patients with advanced/metastatic solid tumors. FDA018-ADC is administered via intravenous infusion using an accelerated titration method followed by a conventional 3 + 3 study design to identify the maximum tolerated dose (MTD) and dose-limiting toxicities（DLT）during 35-day cycle with 3 doses. The expansion phase enrolled patients into three cohorts defined by tumor type: cohort 1 included patients with locally advanced or metastatic TNBC; cohort 2 included patients with non-small-cell lung cancer (NSCLC); and cohort 3 included those with other locally advanced or metastatic solid tumors. The efficacy and safety, as well as the recommended phase 2 dose (RP2D) were determined in this phase.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients able to give written informed consent;
- •Age ≥ 18 and ≤ 75 years old, male or female;
- •Patients have histological or cytological diagnosis with advanced solid tumors, cann't benefit from existing standard treatment options, and are not suitable for surgical resection or radiation therapy for the purpose of cure; tumor types in the study include: triple-negative breast cancer (TNBC), urothelial cancer (UC), non-small-cell lung cancer (NSCLC), small-cell lung cancer (SCLC), endometrial, gastric adenocarcinoma, esophageal, ovarian, colorectal and so on.
- •Have measurable lesions defined in RECIST v. 1.1;
- •Expected survival ≥ 12 weeks;
- •Eastern Cancer Cooperative Group (ECOG) performance status 0-1;
- •Adequate bone marrow, hepatic, and renal function;
- •All acute toxicity of previous anti-tumor treatment or surgery is relieved to baseline severity or NCI CTCAE version 5.0 ≤ 1;
- •Tumor tissue sections available；
- •Patients of child bearing potential must agree to take contraception during the study and for 6 months after the last day of treatment.
排除标准
- •Previous treatments for anti-Trop-2 antibody or other treatments against Trop-2, such as IMMU-132;
- •Have history of an anaphylactic reaction to irinotecan or ≥ Grade 3 GI toxicity to prior irinotecan, or previously allergic to macromolecular protein preparations;
- •Have had other malignant tumors in the past 5 years;
- •Received other anti-tumor treatments (including chemotherapy, radiotherapy, Targeted therapy, immunotherapy, experimental treatment and so on) within 4 weeks;
- •Infection requiring intravenous antibiotic use within 1 week or Fever of unknown cause occurred before the first administration> 38.5℃；
- •Have CNS (central nervous system) metastasis with clinical symptoms;
- •Any of the following cardiac criteria:
- •Known history of severe heart disease, such as CHF≥ level 2, NYHA≥ level 2 and angina requiring medication;
- •Clinically significant cardiac arrhythmia requiring anti-arrhythmia therapy;
- •Hypertension not controlled by medication;
- •Have history of clinical significant active COPD, or other moderate-to-severe chronic respiratory illness present within 6 months;
- •Patients with poorly controlled diabetes;
- •Suffering from active chronic inflammatory bowel disease (ulcerative colitis, Crohn disease), and history of intestinal obstruction, or GI perforation;
- •Patients who had undergone major surgery or severe trauma within 4 weeks prior to the first dose;
- •Patients who had undergone autologous within 3 months of initiation of study treatment or allogeneic organ or stem cell transplantation within 6 months of initiation of study treatment;
- •Clinically active bacterial, fungal or viral infections (eg active hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV), syphilis positive and so on);
- •Patients who had undergone systemic high-dose steroids within 2 weeks of initiation of study treatment;
- •Occurrence of serious venous/venous thrombosis within 1 year prior to the first dose, such as cerebrovascular accidents (including transient ischemic attack), deep vein thrombosis and pulmonary embolism;
- •Patients have history of psychotropic drug abuse, alcohol or drug abuse；
- •Women who are pregnant or lactating；
- •Any condition that is unstable or may jeopardize patient safety and its compliance with the study;
- •Other circumstances that is deemed not appropriate for the study.
研究组 & 干预措施
FDA018-ADC A mg/kg
Subjects will receive FDA018-ADC A mg/kg of body weight via intravenous (IV) infusion on Day 1 of a 14-Day cycle (Cycle 1) and on Day 1 and 8 of a 21-day cycle (Cycle 2 ~ Cycle n) in dose escalation phase, and on Day 1 and 8 of a 21-day cycle(Cycle 1 ~ Cycle n) in dose expansion phase, until the date of first documented progression or unacceptable toxicity or death.
干预措施: FDA018-ADC (Drug)
FDA018-ADC B mg/kg
Subjects will receive FDA018-ADC B mg/kg of body weight via intravenous (IV) infusion on Day 1 of a 14-Day cycle (Cycle 1) and on Day 1 and 8 of a 21-day cycle (Cycle 2 ~ Cycle n) in dose escalation phase, and on Day 1 and 8 of a 21-day cycle(Cycle 1 ~ Cycle n) in dose expansion phase, until the date of first documented progression or unacceptable toxicity or death.
干预措施: FDA018-ADC (Drug)
FDA018-ADC C mg/kg
Subjects will receive FDA018-ADC C mg/kg of body weight via intravenous (IV) infusion on Day 1 of a 14-Day cycle (Cycle 1) and on Day 1 and 8 of a 21-day cycle (Cycle 2 ~ Cycle n) in dose escalation phase, and on Day 1 and 8 of a 21-day cycle(Cycle 1 ~ Cycle n) in dose expansion phase, until the date of first documented progression or unacceptable toxicity or death.
干预措施: FDA018-ADC (Drug)
FDA018-ADC D mg/kg
Subjects will receive FDA018-ADC D mg/kg of body weight via intravenous (IV) infusion on Day 1 of a 14-Day cycle (Cycle 1) and on Day 1 and 8 of a 21-day cycle (Cycle 2 ~ Cycle n) in dose escalation phase, and on Day 1 and 8 of a 21-day cycle(Cycle 1 ~ Cycle n) in dose expansion phase, until the date of first documented progression or unacceptable toxicity or death.
干预措施: FDA018-ADC (Drug)
FDA018-ADC E mg/kg
Subjects will receive FDA018-ADC E mg/kg of body weight via intravenous (IV) infusion on Day 1 of a 14-Day cycle (Cycle 1) and on Day 1 and 8 of a 21-day cycle (Cycle 2 ~ Cycle n) in dose escalation phase, and on Day 1 and 8 of a 21-day cycle(Cycle 1 ~ Cycle n) in dose expansion phase, until the date of first documented progression or unacceptable toxicity or death.
干预措施: FDA018-ADC (Drug)
FDA018-ADC F mg/kg
Subjects will receive FDA018-ADC F mg/kg of body weight via intravenous (IV) infusion on Day 1 of a 14-Day cycle (Cycle 1) and on Day 1 and 8 of a 21-day cycle (Cycle 2 ~ Cycle n) in dose escalation phase, and on Day 1 and 8 of a 21-day cycle(Cycle 1 ~ Cycle n) in dose expansion phase, until the date of first documented progression or unacceptable toxicity or death.
干预措施: FDA018-ADC (Drug)
FDA018-ADC G mg/kg
Subjects will receive FDA018-ADC G mg/kg of body weight via intravenous (IV) infusion on Day 1 of a 14-Day cycle (Cycle 1) and on Day 1 and 8 of a 21-day cycle (Cycle 2 ~ Cycle n) in dose escalation phase, and on Day 1 and 8 of a 21-day cycle(Cycle 1 ~ Cycle n) in dose expansion phase, until the date of first documented progression or unacceptable toxicity or death.
干预措施: FDA018-ADC (Drug)
结局指标
主要结局
The maximum tolerated dose (MTD)
时间窗: From first dose to the end of Cycle 1, up to 35 days.
Maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 or more in a cohort of either 3 or 6 patients experiences a dose limiting toxicity (DLT) attributed to FDA018.
The dose limiting toxicity ( DLT)
时间窗: From first dose to the end of Cycle 1, up to 35 days.
Evaluated according to NCI CTCAE V5.0
Adverse Events
时间窗: From subject randomization up to 60 months
To check the numbers of AEs happened during the course of trial.
Objective Response Rate (ORR) according to RECIST 1.1
时间窗: From subject randomization up to 60 months.
ORR was defined as the rate an overall best response of either complete response (CR) or partial response (PR) according to RECIST1.1. CR was defined as the disappearance of all target lesions and reduction in short axis of any pathologic lymphnode to \<10 mm. PR was defined as ≥ 30% decrease in the sum of diameters of target lesions, taking the baseline sum diameters.
Recommended phase II dose (RP2D)
时间窗: From subject randomization up to 60 months.
次要结局
- Progression free survival(PFS) according to RECIST 1.1(From subject randomization up to 60 months.)
- Duration of Response(DOR) according to RECIST 1.1(From subject randomization up to 60 months.)
- Overall Survival (OS) according to RECIST 1.1(From subject randomization up to 60 months.)
- Half-life time (t1/2)(Up to 17 weeks.)
- Area under the plasma concentration versus time curve (AUC)(Up to 17 weeks.)
- Number of subjects who develop detectable anti-drug antibodies (ADAs)(From subject randomization up to 60 months.)
- Time to peak (Tmax)(Up to 17 weeks.)
- Peak Plasma Concentration (Cmax)(Up to 17 weeks.)