Open-label, multicenter, phase 1 study to investigate the safety, tolerability, and PK of AN4005 in patients with advanced tumors. This study is a first-in-human, dose escalation study with the objective to establish the MTD and/or RP2D of AN4005. Except for Dose Level 0 (50 mg), a traditional "3 + 3 design" will be utilized for dose finding with dose escalation and/or de-escalation as appropriate.
In this study, one sentinel patient will be dosed at 50 mg first, then increasing doses of AN4005 will be administered to cohorts of 3 subjects, at doses ranging from 100 mg twice daily (BID) to 600 mg BID (see the table below). The proposed starting dose, 50 mg BID, has been selected based on integrated data from nonclinical studies. If 50 mg BID for one cycle is deemed to be tolerable upon review of safety data, the dose of AN4005 will be escalated to 100 mg BID in a cohort of 3 patients, and further dose escalations will be performed in separate cohorts based on review of data from all preceding cohorts. The dose escalation will be conducted in a sequential manner. Intermediate dose levels (decrement) may be explored. Decisions with regard to dose escalation to next dose level will be made jointly by the investigators and the sponsor. AE data collected for approximately 90 days following the end of exposure will also be used to inform the final dose and schedule. A minimum of 6 patients will be treated at the MTD/RP2D.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
31
50mg BID
100mg BID
200mg BID
Hackensack University Medical Center
Hackensack, New Jersey, United States
RECRUITINGMontefiore Einstein Cancer Center
The Bronx, New York, United States
RECRUITINGPrisma Health Institute for Translational Oncology Research
Greenville, South Carolina, United States
Number of participants with any adverse events (AEs), serious adverse events (SAEs), withdrawal due to AEs, dose interruptions and reductions
All AEs, SAEs and dose modifications will be collected
Time frame: Up to approximately 1 year
Number of participants with dose limiting toxicities (DLTs)
An event is considered to be a DLT if the event occurs within the first 28 days of treatment and meets the dose-limiting toxicity criteria, unless it can be clearly established that the event is unrelated to treatment
Time frame: Up to 28 days
Number of participants with clinically significant changes in laboratory parameters, vital signs, physical examination and organ-specific parameters
Blood and urine samples will be collected for analysis of lab parameters. Vital signs, physical examinations and organ-specific parameters will be collected at specified time points
Time frame: Up to approximately 1 year
Maximum observed plasma concentration (Cmax) of AN4005
Blood samples will be collected at given time points to determine the Cmax of AN4005
Time frame: Baseline and up to approximately 1 year
Area under the plasma concentration-time curve (AUC) extrapolated from time zero to infinity (AUC[0-inf]) of AN4005
Blood samples will be collected at given time points to determine the AUC (0-inf) of AN4005
Time frame: Up to approximately 1 year
AUC from time zero to the last quantifiable concentration after dosing (AUC[0-t]) of AN4005
Blood samples will be collected at given time points to determine the AUC (0-t) of AN4005
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400mg BID
600mg BID
Dose to be determined upon the MTD determination
Next Virginia
Fairfax, Virginia, United States
RECRUITINGBeijing Cancer Hospital
Beijing, Beijing Municipality, China
RECRUITINGHarbin Medical University Cancer Hospital
Harbin, Heilongjiang, China
RECRUITINGUnion Hospital Tongji Medical College Huazhong University of Science and Technology
Wuhan, Hubei, China
RECRUITINGTime frame: Up to approximately 1 year
AUC over the dosing interval tau (AUC[0-tau]) of AN4005
Blood samples will be collected at given time points to determine the AUC (0-tau) of AN4005
Time frame: Up to approximately 1 year
Terminal phase half-life (t1/2) of AN4005
Blood samples will be collected at given time points to determine the half-life of AN4005
Time frame: Up to approximately 1 year
Oral clearance (CL/F) of AN4005
Blood samples will be collected at given time points to determine the CL/F of AN4005
Time frame: Up to approximately 1 year
Accumulation ratio (AR) of AN4005
Blood samples will be collected at given time points to determine the AR of AN4005
Time frame: Up to approximately 1 year
Participants with solid tumors: Overall response rate (ORR) based on Evaluation Criteria In Solid Tumors (RECIST) 1.1
ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. All solid tumor cohorts will score ORR by investigator assessment
Time frame: Up to approximately 1 year
Participants with lymphoma: ORR based on Lugano criteria
ORR is defined as the percentage of participants achieving CR or PR based on Lugano criteria
Time frame: Up to approximately 1 year
Evaluate progression free survival (PFS) of participants
PFS is defined as the time of participants free from first dose of treatment until radiographic progression based on RECIST 1.1 or Lugano criteria or death due to any cause, whichever is earlier. Median PFS will be estimated using the Kaplan-Meier product limit method and provided graphically
Time frame: Up to approximately 1 year
Evaluate disease control rate (DCR) of participants
DCR is defined as the proportion of patients with a BOR of CR, PR or stable disease (SD) by investigator review
Time frame: Up to approximately 1 year
Evaluate duration of Response (DOR) of participants
DOR is defined as the time from first evidence of response (CR or PR per RECIST 1.1) to earlier date of disease progression or death due to any cause, as determined by ICR
Time frame: Up to approximately 1 year
Evaluate complete remission rate (CRR) of participants
CRR is defined as the proportion of patients with a best overall response of CR by investigator review. For Lugano 2014 Criteria for lymphomas, CR is defined as disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of spleen, liver, and bone marrow involvement
Time frame: Up to approximately 1 year
Evaluate overall survival (OS) of participants
OS is defined as the time from first dose of AN4005 until death from any cause
Time frame: Up to approximately 1 year