A PhaseⅠStudy to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of FDA018-ADC in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- FDA018-ADC
- Conditions
- Advanced/ Metastatic Solid Tumors
- Sponsor
- Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd.
- Enrollment
- 78
- Locations
- 1
- Primary Endpoint
- The maximum tolerated dose (MTD)
- Status
- Active, Not Recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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;
Arms & Interventions
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.
Intervention: FDA018-ADC
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.
Intervention: FDA018-ADC
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.
Intervention: FDA018-ADC
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.
Intervention: FDA018-ADC
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.
Intervention: FDA018-ADC
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.
Intervention: FDA018-ADC
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.
Intervention: FDA018-ADC
Outcomes
Primary Outcomes
The maximum tolerated dose (MTD)
Time Frame: 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)
Time Frame: From first dose to the end of Cycle 1, up to 35 days.
Evaluated according to NCI CTCAE V5.0
Adverse Events
Time Frame: 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
Time Frame: 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)
Time Frame: From subject randomization up to 60 months.
Secondary Outcomes
- 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.)