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TerminatedNCT04645797Updated Aug 6, 2025Results posted

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

A Phase 1 interventional study of APR003 in Advanced Colorectal Carcinoma, sponsored by Apros Therapeutics, Inc. Terminated at 4 sites in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2025-08-06.

Sponsored by Apros Therapeutics, Inc · Phase 1, Interventional, and Treatment

Why this study was terminated
Study terminated prematurely due to internal corporate decision
Phase
Phase 1
Study type
Interventional
Enrollment
11
Allocation
Not applicable
Ages
18 Years to 75 Years
Sex
All
01

Study summary

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.

02

Conditions studied

  • Advanced Colorectal Carcinoma
03

In context

Lead sponsor

This is the only study on the registry with Apros Therapeutics, Inc as lead sponsor.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

Exclusion Criteria:

  • Current or history of CNS metastases
  • Significant cardiovascular disease
  • Pregnant or breastfeeding
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
11 participants (actual)

Study arms

  • 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

Interventions

  • DrugAPR003

    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.

06

What researchers measure

Primary outcomes

  1. 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

  2. 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)

  3. 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)

  4. 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)

  5. 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)

  6. 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.

    Time frame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days)

  7. 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)

  8. 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)

  9. 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)

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

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

07

Results

Posted Aug 6, 2025
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.

Participant flow

Participant flow — Overall Study
MilestoneCohort -1Cohort 1Cohort 2Cohort 3Cohort 4Cohort 5Cohort 6
Started6410000
Completed0000000
Not completed6410000
Withdrew: Disease progression3310000
Withdrew: Death3100000

Outcome measures

PrimaryDetermine 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
Reported as:
Number · participants
Determine the Number of Patients With Dose Limiting Toxicities (DLTs)
participantsCohort -1Cohort 1Cohort 2
Determine the Number of Patients With Dose Limiting Toxicities (DLTs)001
PrimaryMaximum 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)
Reported as:
Mean · ng/mL
Maximum Concentration (Cmax) of APR003
ng/mLCohort -1Cohort 1Cohort 2
Cycle 1 Day 1224 ± 124158 ± 85.4—
Cycle 1 Day 15362 ± 150148 ± 85.4—
Cycle 2 Day 1217 ± 157121 ± 65.3—
PrimaryTime-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)
Reported as:
Mean · hr
Time-to-maximum Concentration (Tmax) of APR003
hrCohort -1Cohort 1Cohort 2
Cycle 1 Day 10.750 (0.5 to 2)2.00 (0.5 to 2)—
Cycle 1 Day 151.00 (0.5 to 1)2.00 (1 to 4)—
Cycle 2 Day 11 (0.5 to 4)2.00 (2 to 4)—
PrimaryArea 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)
Reported as:
Mean · ng*hr/mL
Area Under the Curve (AUC) From Time Zero to 24 hr (AUC0-24) of APR003
ng*hr/mLCohort -1Cohort 1Cohort 2
Cycle 1 Day 1597 ± 209489 ± 137—
Cycle 1 Day 15862 ± 355412 ± 89—
PrimaryAUC 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)
Reported as:
Mean · ng*hr/mL
AUC From Time Zero to Time Infinity (AUC0-ꝏ) of APR003
ng*hr/mLCohort -1Cohort 1Cohort 2
AUC From Time Zero to Time Infinity (AUC0-ꝏ) of APR003601 ± 212497 ± 134—
PrimaryAUC 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.

Time frame:
Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days)
Reported as:
Mean · ng*hr/mL
AUC Over the Dosing Interval (AUClast) of APR003
ng*hr/mLCohort -1Cohort 1Cohort 2
Cycle 1 Day 1597 ± 209489 ± 137—
Cycle 1 Day 15830 ± 330443 ± 112—
Cycle 2 Day 1525 ± 370335 ± 147—
PrimaryElimination 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)
Reported as:
Mean · hr
Elimination Half-life (T1/2) of APR003
hrCohort -1Cohort 1Cohort 2
Cycle 1 Day 14.03 ± 0.8164.56 ± 1.29—
Cycle 1 Day 151.78 ± 0.6301.77 ± 0.279—
Cycle 2 Day 11.56 ± 0.485——
PrimaryApparent 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)
Reported as:
Mean · L
Apparent Volume of Distribution at Steady State After Administration (Vss/F) of APR003
LCohort -1Cohort 1Cohort 2
Apparent Volume of Distribution at Steady State After Administration (Vss/F) of APR003265 ± 102711 ± 314—
PrimaryApparent 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)
Reported as:
Mean · L/hr
Apparent Total Plasma Clearance (CL/F) of APR003
L/hrCohort -1Cohort 1Cohort 2
Apparent Total Plasma Clearance (CL/F) of APR00346.0 ± 15.7105 ± 23.1—
SecondaryObjective 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
Reported as:
Count of participants · Participants
Objective Response Rate
ParticipantsCohort -1Cohort 1Cohort 2
Objective Response Rate000

Adverse events

Collected over Until disease progression, or up to approximately 15 months and 18 days, whichever is first. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cohort -13/6 (50%)2/6 (33.3%)6/6 (100%)
Cohort 11/4 (25%)0/4 (0%)3/4 (75%)
Cohort 20/1 (0%)1/1 (100%)1/1 (100%)
Most frequent serious events
Most frequent serious events
EventCohort -1Cohort 1Cohort 2
Cytokine release syndromeImmune system disorders0/60/41/1
Progression of Colon CancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/60/40/1
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/60/40/1
Post-surgical PainInjury, poisoning and procedural complications1/60/40/1
Most frequent other events
Showing 10 of 105
Most frequent other events
EventCohort -1Cohort 1Cohort 2
Worsening diarrheaGastrointestinal disorders0/60/41/1
XerostomiaGastrointestinal disorders0/60/41/1
Mouth soresGastrointestinal disorders0/60/41/1
ConstipationGastrointestinal disorders0/60/41/1
Muscle spasmMusculoskeletal and connective tissue disorders0/60/41/1
Iron deficiency anemiaBlood and lymphatic system disorders0/60/41/1
Oral thrushInfections and infestations0/60/41/1
Chronic UTIInfections and infestations0/60/41/1
Cytokine release syndromeImmune system disorders1/61/41/1
Rash-faceSkin and subcutaneous tissue disorders0/60/41/1

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Cohort -1Cohort 1Cohort 2Total
<=18 years0000
Between 18 and 65 years54110
>=65 years1001
Age, Continuous
Age, Continuous(years)Cohort -1Cohort 1Cohort 2Total
Median50.5 (47 to 74)52 (51 to 64)52 (52 to 52)52 (47 to 74)
Sex: Female, Male
Sex: Female, Male(Participants)Cohort -1Cohort 1Cohort 2Total
Female2013
Male4408
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Cohort -1Cohort 1Cohort 2Total
Hispanic or Latino0101
Not Hispanic or Latino63110
Unknown or Not Reported0000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Cohort -1Cohort 1Cohort 2Total
American Indian or Alaska Native1001
Asian0011
Native Hawaiian or Other Pacific Islander0000
Black or African American0000
White5409
More than one race0000
Unknown or Not Reported0000
Region of Enrollment
Region of Enrollment(participants)Cohort -1Cohort 1Cohort 2Total
United States64111
ECOG Performance Status
ECOG Performance Status(units on a scale)Cohort -1Cohort 1Cohort 2Total
Median1 (0 to 1)0.5 (0 to 1)0 (0 to 0)1 (0 to 1)
Stage at Trial Entry
Stage at Trial Entry(Participants)Cohort -1Cohort 1Cohort 2Total
IVB2417
IV2002
IVC2002

5 further baseline measures are reported on the registry.

08

Study locations

4 sites
  • AdventHealth Orlando
    Orlando, Florida 32803, United States
  • Carolina BioOncology Institute Cancer Research Clinic
    Huntersville, North Carolina 28078, United States
  • NEXT Oncology - Austin
    Austin, Texas 78758, United States
  • NEXT Oncology - San Antonio
    San Antonio, Texas 78229, United States
09

References and documents

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 documents

  • Protocol and statistical analysis plan · Jan 28, 2022
  • Informed consent form · Jan 28, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 6, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04645797
Lead sponsor
Apros Therapeutics, Inc
Responsible party
Sponsor
First posted
Nov 27, 2020
Start date
Jan 19, 2021
Primary completion
May 7, 2022
Completion
May 7, 2022
Results posted
Aug 6, 2025
Last update
Aug 6, 2025

Study contacts

Aaron Weitzman, MD
study director · Apros Therapeutics, Inc
Trinh Le
study director · Apros Therapeutics, Inc

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is terminated, as verified in Jul 2025. You cannot join it, but the record below documents what was studied.

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