Advanced Colorectal CarcinomaPhase 1NCT04645797

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

A Phase 1 study testing APR003 in people with Advanced Colorectal Carcinoma, run by Apros Therapeutics, Inc at 4 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

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

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Advanced Colorectal Carcinoma
What is being tested?: APR003
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 11 participants
Where: 4 sitesUnited States
Study dates: 19 Jan 2021to 7 May 2022
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Show all 9Show fewer

Adequate renal function
Normal coagulation panel
Willingness to use effective contraception

Who cannot join

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

Trial locations and contacts

4 sites in 1 country.

United States4 sites

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

Other trials in United States

About this study

Official title: 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

Read the 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.

Conditions: Advanced Colorectal Carcinoma
Being tested: APR003

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

APR003Drug
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.

Study groups in NCT04645797
Study group	Role	What they receive
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. Receives: Drug: APR003

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Cycle 1 Day 1 (Cycle duration is 21 days)

Secondary outcomes (1)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

19 Jan 20217 May 2022

First posted27 Nov 2020
Study start19 Jan 2021
Primary completion7 May 2022
Study completion7 May 2022

Why it stopped: Study terminated prematurely due to internal corporate decision

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Advanced Colorectal CarcinomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Sequential
Model description: Phase 1 Dose Escalation
Masking: None (open label)
Enrolment: 11 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04645797
Sponsor's protocol ID: APR003-001
Status last verified: Jul 2025
First submitted: 16 Sep 2020
Last updated: 6 Aug 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Advanced Colorectal Carcinoma trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT04645797
Acronym / sponsor ID: APR003-001
Conditions: Advanced Colorectal Carcinoma
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Study terminated prematurely due to internal corporate decision
Enrolment: 11 participants (actual)
Lead sponsor: Apros Therapeutics, IncIndustry (pharma, biotech, devices)
Study start: 19 Jan 2021 (actual)
Primary completion: 7 May 2022 (actual)
Study completion: 7 May 2022 (actual)
First posted: 27 Nov 2020 (actual)
Results: Posted 6 Aug 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Sequential
Masking: None (open label)
Number of arms: 1
Model description: Phase 1 Dose Escalation

Arm	Type	Receives
APR003 Dose Escalation	Experimental	Drug: APR003This 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.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

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

Key exclusion criteria (3 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
APR003This 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.	Drug	APR003 Dose Escalation

Primary outcome

Determine the Number of Patients With Dose Limiting Toxicities (DLTs)
Time frame: Until disease progression, or up to approximately 15 months and 18 days, whichever is first
Determine the number of patients who have experienced a Dose Limiting Toxicities (DLT) evaluated by the investigator based on CTCAE Severity Grade.
Maximum Concentration (Cmax) of APR003
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days)
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-to-maximum Concentration (Tmax) of APR003
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days)
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.
Area Under the Curve (AUC) From Time Zero to 24 hr (AUC0-24) of APR003
Time frame: Cycle 1 Day 1, Cycle 1 Day 15 (Cycle duration is 21 days)
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.
AUC From Time Zero to Time Infinity (AUC0-ꝏ) of APR003
Time frame: Cycle 1 Day 1 (Cycle duration is 21 days)
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.
AUC Over the Dosing Interval (AUClast) of APR003
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days)
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.
Elimination Half-life (T1/2) of APR003
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days)
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.
Apparent Volume of Distribution at Steady State After Administration (Vss/F) of APR003
Time frame: Cycle 1 Day 1 (Cycle duration is 21 days)
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.
Apparent Total Plasma Clearance (CL/F) of APR003
Time frame: Cycle 1 Day 1 (Cycle duration is 21 days)
Plasma concentration of APR003 was analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Standard PK parameters were determined using non-compartmental methods.

1 secondary outcome

Objective Response Rate
Time frame: Until disease progression, or up to approximately 15 months and 18 days, whichever is first

Results and safety

Results posted to the registry on 6 Aug 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort -1	6	0
Cohort 1	4	0
Cohort 2	1	0
Cohort 3	0	0
Cohort 4	0	0
Cohort 5	0	0
Cohort 6	0	0

Primary outcome: Determine the Number of Patients With Dose Limiting Toxicities (DLTs)

Time frame: Until disease progression, or up to approximately 15 months and 18 days, whichever is first. Number. Unit: participants

Measure	Cohort -1 n = 6	Cohort 1 n = 4	Cohort 2 n = 1
Value	0	0	1

Primary outcome: Maximum Concentration (Cmax) of APR003

Time frame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days). Mean (Standard Deviation). Unit: ng/mL

Measure	Cohort -1 n = 6	Cohort 1 n = 4	Cohort 2 n = 0
Cycle 1 Day 1	224 (124)	158 (85.4)	–
Cycle 1 Day 15	362 (150)	148 (85.4)	–
Cycle 2 Day 1	217 (157)	121 (65.3)	–

Population analysed: One patient in Cohort 1 was dose-reduced after the first dose from 50 MG to 25 MG and was included only in the Cycle 1 Day 1 analysis. The only patient in Cohort 2 was not analyzed due to incomplete blood collection.

Primary outcome: Time-to-maximum Concentration (Tmax) of APR003

Time frame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days). Mean (Full Range). Unit: hr

Measure	Cohort -1 n = 6	Cohort 1 n = 4	Cohort 2 n = 0
Cycle 1 Day 1	0.750 (0.5 to 2)	2.00 (0.5 to 2)	–
Cycle 1 Day 15	1.00 (0.5 to 1)	2.00 (1 to 4)	–
Cycle 2 Day 1	1 (0.5 to 4)	2.00 (2 to 4)	–

Primary outcome: Area Under the Curve (AUC) From Time Zero to 24 hr (AUC0-24) of APR003

Time frame: Cycle 1 Day 1, Cycle 1 Day 15 (Cycle duration is 21 days). Mean (Standard Deviation). Unit: ng*hr/mL

Measure	Cohort -1 n = 6	Cohort 1 n = 4	Cohort 2 n = 0
Cycle 1 Day 1	597 (209)	489 (137)	–
Cycle 1 Day 15	862 (355)	412 (89)	–

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Until disease progression, or up to approximately 15 months and 18 days, whichever is first. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort -1	2 of 6 (33.3%)	6 of 6 (100%)	3 of 6
Cohort 1	0 of 4 (0%)	3 of 4 (75%)	1 of 4
Cohort 2	1 of 1 (100%)	1 of 1 (100%)	0 of 1

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
BackgroundMiller 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
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Aaron Weitzman, MD study director

Apros Therapeutics, Inc

Trinh Le study director

Apros Therapeutics, Inc

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing APR003 in people with Advanced Colorectal Carcinoma, run by Apros Therapeutics, Inc at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 6 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determine the Number of Patients With Dose Limiting Toxicities (DLTs) (time frame: Until disease progression, or up to approximately 15 months and 18 days, whichever is first). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04645797, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2025.