This is a first-in-human, multicenter, open-label, dose escalation and dose expansion Phase 1/2 study to determine the MTD and/or the recommended Phase 2 dose (RP2D) and to characterize DLTs of AT-1965 as well as to investigate the safety, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of AT-1965 in patients with advanced, refractory or recurrent solid tumors (nonresectable and/or metastatic) including mTNBC.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
100
AT-1965 Liposome Injection administered intravenously once weekly for the first 3 weeks (Days 1, 8 and 15) of a 4 week cycle.
CBCC Global Research Site 001
Scottsdale, Arizona, United States
RECRUITINGCBCC Global Research Site 005
Bakersfield, California, United States
WITHDRAWNCBCC Global Research Site 007
El Segundo, California, United States
RECRUITINGCBCC Global Research Site 008
Santa Monica, California, United States
RECRUITINGCBCC Global Research Site 009
Santa Monica, California, United States
RECRUITINGCBCC Global Research Site 003
Stanford, California, United States
RECRUITINGCBCC Global Research Site 010
New York, New York, United States
NOT_YET_RECRUITINGCBCC Global Research Site 002
Portland, Oregon, United States
RECRUITINGCBCC Global Research Site 006
Dallas, Texas, United States
RECRUITINGDose Limiting Toxicity (DLT) according to CTCAE version 5.0 in Part A - Dose Escalation Phase
Nature and frequency of dose-limiting toxicities (DLTs) associated with AT-1965 administration, maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D)
Time frame: Dose limiting toxicities will be evaluated during the first treatment cycle (28 days)
Objective Response Rate (ORR) based on RECIST version 1.1 in Part B - Dose Expansion Phase
Objective Response Rates (ORR) defined as proportion of patients with a best overall response of complete response (CR) or partial response (PR) according to RECISTv1.1 as assessed by the Investigator
Time frame: 3, 6 and 9 month
Duration of Response (DoR) based on RECIST version 1.1 in Part B - Dose Expansion Phase
Duration of response (DoR) defined as the duration of overall response measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented according to RECIST v1.1 as assessed by the Investigator.
Time frame: 3, 6 and 9 month
Area under the concentration-time curve from zero to a definite time [AUC(0-t)]
Pharmacokinetic profile of AT-1965 measured by AUC(0-t)
Time frame: Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study)
Area under the concentration-time curve from zero to 168 hours [AUC(0-168)]
Pharmacokinetic profile of AT-1965 measured by AUC(0-168)
Time frame: Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study)
Area under the concentration-time curve from zero to 24 hours
Pharmacokinetic profile of AT-1965 measured by AUC(0-24)
Time frame: Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study)
Area under the concentration-time curve from zero to an infinite time [AUC(0-inf)]
Pharmacokinetic profile of AT-1965 measured by AUC(0-inf)
Time frame: Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study)
Maximum plasma concentration [Cmax]
Pharmacokinetic profile of AT-1965 measured by Cmax
Time frame: Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study)
Minimum plasma concentration [Cmin]
Pharmacokinetic profile of AT-1965 measured by Cmin
Time frame: Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study)
Time to maximum plasma concentration [tmax]
Pharmacokinetic profile of AT-1965 measured by tmax
Time frame: Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study)
Elimination half-life [t1/2]
Pharmacokinetic profile of AT-1965 measured by t1/2
Time frame: Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study)
Volume of distribution [Vz/F]
Pharmacokinetic profile of AT-1965 measured by Vz/F
Time frame: Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study)
Clearance (CL/F)
Pharmacokinetic profile of AT-1965 measured by CL/F
Time frame: Days 1, 8, and 15 of each treatment cycle (duration of each treatment cycle will be 28 days in both parts of the study)
The number of Adverse Events (AE) that occurs
All AEs will be graded according to CTCAE version 5.0 Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe or medically significant but not immediately life-threatening, Grade 4: Life-threatening consequences Grade 5: Death related to AE
Time frame: Adverse events will be recorded from informed consent through 30 days after the last dose of study drug
Laboratory Parameters
Incidence of clinically significant clinical laboratory abnormalities (hematology, clinical chemistry, coagulation, and urinalysis)
Time frame: Screening, Days 1, 8, and 15 of each treatment cycle (each cycle is 28 days)
The number of Serious Adverse Events (SAE) that occurs
Time frame: SAEs will be recorded from the start of the first dose of AT-1965 (Cycle 1 Day 1) up to 30 days after the last dose of study drug or until resolution or stabilization of SAEs
Clinical Benefit Ratio (CBR) based on RECISTv1.1 and iRECIST
Clinical Benefit Rate (CBR) defined as the percentage of patients who have achieved complete response, partial response and stable disease according to RECISTv1.1 and iRECIST as assessed by the Investigator.
Time frame: 3, 6 and 9 month
Duration of Clinical Benefit (DoCB) based on RECISTv1.1 and iRECIST
Duration of Clinical Benefit (DoCB) defined as the time from randomization to disease progression in patients who achieve complete response, partial response, or stable disease according to RECISTv1.1 and iRECIST as assessed by the Investigator.
Time frame: 3, 6 and 9 month
Progression-free survival (PFS) based on RECIST version 1.1
Progression-free survival (PFS), defined as the time from first dose to confirmed progression of disease (PD) or death, according to RECIST v1.1 as assessed by the Investigator.
Time frame: 3, 6 and 9 month
Best Overall Response (BOR) based on RECISTv1.1 and iRECIST
Best Overall response (BOR) defined as the best response across all time points (for example, a patient who has SD at first assessment, PR at second assessment, and PD on last assessment has a best overall response of PR) according to RECISTv1.1 and iRECIST as assessed by the Investigator.
Time frame: 3, 6 and 9 month
Overall Survival (OS) based on RECISTv1.1 and iRECIST
Overall Survival (OS) is defined as the time from the date of first dose of study treatment to the date of death due to any cause.
Time frame: 3, 6 and 9 month
Time to next treatment (TTNT)
Time to next treatment (TTNT), defined as the time from start date of AT-1965 to start date of the next line of anti-cancer therapy.
Time frame: 3, 6 and 9 month
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