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

NCT04645797 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: APR003-001
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Advanced Colorectal Carcinoma

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (1)

• Objective Response Rate

  Until disease progression, or up to approximately 15 months and 18 days, whichever is first

Study Arms (1)

APR003 Dose Escalation

EXPERIMENTAL

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

Interventions

APR003 DRUG

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.

APR003 Dose Escalation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Apros Therapeutics, Inc: lead

Study Sites (4)

AdventHealth Orlando

Orlando, Florida, 32803, United States

Location

Carolina BioOncology Institute Cancer Research Clinic

Huntersville, North Carolina, 28078, United States

Location

NEXT Oncology - Austin

Austin, Texas, 78758, United States

Location

NEXT Oncology - San Antonio

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• 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

  BACKGROUND

Limitations and Caveats

The primary limitation of this study was its small sample size. While it is difficult to draw firm conclusions on such a small cohort of patients, several preliminary conclusions can be drawn.

Results Point of Contact

• Title: Tom Wu, PhD
• Organization: Apros Therapeutics

tom_wu@aprostx.com

+1-858-284-8839

Study Officials

• Aaron Weitzman, MD

  Apros Therapeutics, Inc

  STUDY DIRECTOR

• Trinh Le

  Apros Therapeutics, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1 Dose Escalation

Study Record Dates

• First Submitted: September 16, 2020
• First Posted: November 27, 2020
• Study Start: January 19, 2021
• Primary Completion: May 7, 2022
• Study Completion: May 7, 2022
• Last Updated: August 6, 2025
• Results First Posted: August 6, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)