A Dose Escalation Study of APR003 in Patients With Advanced Colorectal Cancer (CRC) With Malignant Liver Lesions

A Phase 1 Dose Escalation Study to Evaluate Safety, Tolerability, and Pharmacokinetics/ Pharmacodynamics of APR003 in Patients With Advanced Colorectal Cancer (CRC) With Malignant Liver Lesions

A Phase 1 dose escalation study to evaluate APR003 in patients with advanced colorectal cancer (CRC) with malignant liver lesions

Study Overview

• Status: Terminated
• Conditions: Advanced Colorectal Carcinoma
• Intervention / Treatment: Drug: APR003

Detailed Description

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
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32803
      • AdventHealth Orlando
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Carolina BioOncology Institute Cancer Research Clinic
  • Texas
    • Austin, Texas, United States, 78758
      • NEXT Oncology - Austin
    • San Antonio, Texas, United States, 78229
      • NEXT Oncology - San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ECOG performance status of 0 or 1
• Must have disease that is considered non-surgically resectable.
• Relapsed or persistent/refractory to at least two prior systemic treatment regimens for locally advanced or metastatic disease considered to be standard-of-care (SOC).
• Must have previously received an irinotecan or oxaliplatin-based therapy, as well as a targeted antibody therapy for metastatic disease
• Tumors that are MSI-H/dMMR must have previously received checkpoint inhibitor therapy
• Adequate hepatic function
• Adequate renal function
• Normal coagulation panel
• Willingness to use effective contraception

Exclusion Criteria:

• Current or history of CNS metastases
• Significant cardiovascular disease
• Pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: APR003 Dose Escalation; This portion of the study will evaluate the safety and pharmacokinetics of a range of APR003 doses administered once a week for 21 days in subjects with advance colorectal cancer (CRC) with metastases to the liver and to determine the RP2D.	Drug: APR003; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	Cycle 1 Day 1 (Cycle duration is 21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Until disease progression, or up to approximately 15 months and 18 days, whichever is first

Collaborators and Investigators

• Sponsor: Apros Therapeutics, Inc
• Investigators: Study Director: Aaron Weitzman, MD, Apros Therapeutics, Inc; Study Director: Trinh Le, Apros Therapeutics, Inc

Publications and helpful links

General Publications

• Miller A, Le T, Holland J, et al1167 APR003, an oral liver- and GI-targeted TLR7 agonist, elicits a robust type I interferon response in advanced colorectal cancer patientsJournal for ImmunoTherapy of Cancer 2022;10:doi: 10.1136/jitc-2022-SITC2022.1167

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2021
• Primary Completion (Actual): May 7, 2022
• Study Completion (Actual): May 7, 2022

Study Registration Dates

• First Submitted: September 16, 2020
• First Submitted That Met QC Criteria: November 22, 2020
• First Posted (Actual): November 27, 2020

Study Record Updates

• Last Update Posted (Actual): August 6, 2025
• Last Update Submitted That Met QC Criteria: July 31, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms
• Other Study ID Numbers: APR003-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No