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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Advanced Colorectal Carcinoma

Intervention / Treatment
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* Drug: APR003


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Phase 1 Dose Escalation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: APR003 Dose Escalation<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Outcome Measure | Determine Maximum Tolerated Dose and/or Recommended Dose within the test APR003 dose range | Up to one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Outcome | Overall Response Rate | Up to three years |