Study Design
3+3 dose-escalation trial conducted 2019-2021. ClinicalTrials.gov: NCT04811898.
First-in-Human Oncology
Phase 1a clinical results: PRX-474
Completed dose-escalation trial in 17 patients with advanced solid tumors who had failed all prior standard-of-care therapies.
Trial Overview
Patients Enrolled
17 cancer patients evaluated for response. Diagnoses included pancreatic, glioblastoma, CRC, HCC, breast, ovarian, gastric, and peritoneal mesothelioma.
Dose Range
0.5 to 5 mg/kg tested. All patients had failed previous standard-of-care therapies.
Key Results
Safety and Efficacy
Safety (Primary Outcome)
0grade 3-4 toxicities
Well tolerated across all dose levels (0.5-5 mg/kg). MTD was not reached.
5 mg/kg
Recommended dose for future trials.
Efficacy (Secondary Outcome)
56%disease control rate
Stable disease in 50% of patients, partial response in 6.25% (CRC). Total SD + PR: 56.25%.
44+months durable response
Metastatic CRC patient alive with excellent performance status at 44+ months.
The excellent safety profile, the promising bio-modulatory and the anti-tumor activity strongly support translation into a Phase 1b / Phase 2a trial.View on ClinicalTrials.gov
Pharmacodynamics
Mechanism confirmed
The trial demonstrated concentration-dependent downregulation of miR-221 and upregulation of its canonical targets, confirming the LockMiR mechanism of action in patients.
Unexpected Clinical Benefit: CIPN
During the Phase 1a trial, symptomatic clinical benefit was observed in patients affected by chemotherapy-induced peripheral neuropathy (CIPN), a debilitating side effect with no current FDA-approved treatment. Among 13 patients who experienced CIPN, improvement was documented on the PGC neurological assessment scale.
What's Next
Path to Phase 1b/2a
The excellent safety profile and promising anti-tumor activity support advancement into a confirmatory dose optimization and expansion trial as a single agent and/or combination in advanced HCC and CRC.
Primary Endpoints
Safety and tolerability.
Secondary Endpoints
PK/PD and immunogenicity.
Exploratory Endpoints
Disease Control Rate (DCR), Objective Response Rate (ORR), Progression-Free Survival (PFS), biomarker profile, and CIPN.