A Phase 1 dose escalation study to evaluate APR003 in patients with advanced colorectal cancer (CRC) with malignant liver lesions
APR003 is a small molecule TLR7 agonist that concentrates in the GI, and liver with limited systemic exposure. It is designed to increase the therapeutic window of a TLR7 agonist by minimizing the side-effects associated with generalized systemic immune activation and inflammation.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
11
This portion of the study further explores the clinical activity, safety, pharmacokinetics and pharmacology of APR003 monotherapy at the RP2D and to assess the antitumor activity of APR003 in subjects with unresectable CRC with liver metastases.
AdventHealth Orlando
Orlando, Florida, United States
Carolina BioOncology Institute Cancer Research Clinic
Huntersville, North Carolina, United States
NEXT Oncology - Austin
Austin, Texas, United States
NEXT Oncology - San Antonio
San Antonio, Texas, United States
Determine the Number of Patients With Dose Limiting Toxicities (DLTs)
Determine the number of patients who have experienced a Dose Limiting Toxicities (DLT) evaluated by the investigator based on CTCAE Severity Grade.
Time frame: Until disease progression, or up to approximately 15 months and 18 days, whichever is first
Maximum Concentration (Cmax) of APR003
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days)
Time-to-maximum Concentration (Tmax) of APR003
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days)
Area Under the Curve (AUC) From Time Zero to 24 hr (AUC0-24) of APR003
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.
Time frame: Cycle 1 Day 1, Cycle 1 Day 15 (Cycle duration is 21 days)
AUC From Time Zero to Time Infinity (AUC0-ꝏ) of APR003
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.
Time frame: Cycle 1 Day 1 (Cycle duration is 21 days)
AUC Over the Dosing Interval (AUClast) of APR003
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.
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Time frame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days)
Elimination Half-life (T1/2) of APR003
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days)
Apparent Volume of Distribution at Steady State After Administration (Vss/F) of APR003
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.
Time frame: Cycle 1 Day 1 (Cycle duration is 21 days)
Apparent Total Plasma Clearance (CL/F) of APR003
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.
Time frame: Cycle 1 Day 1 (Cycle duration is 21 days)
Objective Response Rate
Objective response rate (ORR), defined as the proportion of patients with either a complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1
Time frame: Until disease progression, or up to approximately 15 months and 18 days, whichever is first