Trials / Recruiting

RecruitingNCT07147231

Testing the Effectiveness of the Anti-cancer Drug Pidnarulex (CX-5461), in Combination With Another Anti-cancer Drug Cemiplimab (REGN2810), in Treating Refractory Microsatellite Stable Colorectal Cancer

A Phase 1 and Randomized Phase 2 Trial of Pidnarulex (CX-5461) and Cemiplimab (REGN2810) in Refractory Microsatellite Stable Colorectal Cancer

Status: Recruiting
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 86 (estimated)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the side effects and best dose of pidnarulex when given together with cemiplimab and to see how well it works in treating patients with microsatellite stable (MSS) colorectal cancer (CRC) that does not respond to treatment (refractory). Pidnarulex may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving pidnarulex with cemiplimab may be safe, tolerable and/or effective in treating patients with refractory MSS CRC.

Detailed description

PRIMARY OBJECTIVES: I. To establish the recommended phase 2 dose of pidnarulex (CX-5461) with anti-programmed cell death protein 1 (PD-1) in phase 1, and to determine safety and tolerability of pidnarulex (CX-5461) alone, and in combination with anti-PD-1 in phases 1 and 2. II. To determine the progression-free survival (PFS) of pidnarulex (CX-5461) alone and in combination with anti-PD-1 in patients with refractory liver metastatic microsatellite stable (MSS) colorectal cancer (CRC) associated with replication stress in phase 2. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To compare the objective response rate (ORR) and disease control rate (DCR) of patients treated with pidnarulex (CX-5461) alone and in combination with anti-PD-1 in phase 2. III. To compare the duration of response (DoR) of patients treated with pidnarulex (CX-5461) alone and in combination with anti-PD-1 in phase 2. IV. To compare the overall survival (OS) of patients treated with pidnarulex (CX-5461) alone and in combination with anti-PD-1 in phase 2. V. To evaluate plasma pharmacokinetic (PK) profiles of pidnarulex (CX-5461) alone and in combination with anti-PD-1. VI. To evaluate the plasma PK profile of cemiplimab. VII. To explore gene signature patterns at baseline or following treatment that may suggest, response to pidnarulex (CX-5461) alone or in combination with anti-PD-1, by whole exome sequencing (WES) and ribonucleic acid (RNA) sequencing in tumor tissue and cell-free deoxyribonucleic acid (DNA) in peripheral blood in phase 2. EXPLORATORY OBJECTIVES: I. To evaluate the baseline expression of MYC and CCNE1 in tumor tissue and its association with response to treatment, as identified by immunohistochemistry in phase 2. II. To evaluate the stimulator of interferon genes (STING) pathway activation and immune cell profile in the tumor at baseline and after treatment with pidnarulex (CX-5461) alone or in combination with anti-PD-1, and its association with response to treatment, as identified by immunohistochemistry in phase 2. III. To evaluate replication stress at baseline and after treatment, and its association with response to treatment, as identified by immunohistochemistry in phase 2. IV. To explore pidnarulex (CX-5461) target engagement, as identified by 47S pre-ribosomal ribonucleic acid (rRNA) in-situ hybridization in phase 2. V. To explore DNA alterations in circulating-tumor deoxyribonucleic acid (ctDNA) and their potential correlation with response to treatment in phase 2. OUTLINE: This is a phase I, dose-escalation study of pidnarulex in combination with cemiplimab followed by a phase II study. PHASE I: Patients receive cemiplimab intravenously (IV) over 30 minutes on days 1 and 15 of each cycle and pidnarulex IV over 60 minutes on days 1 and 8 of each cycle. Cycles repeat every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection on study and computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET)/CT throughout the trial. PHASE II: Patients are randomized to 1 of 2 arms. ARM I: Patients receive pidnarulex IV over 60 minutes on days 1 and 8 of each cycle. Cycles repeat every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsy and CT, MRI, or PET/CT throughout the trial. Additionally, patients undergo blood sample collection on study. ARM II: Patients receive cemiplimab IV over 30 minutes on days 1 and 15 of each cycle and pidnarulex IV over 60 minutes on days 1 and 8 of each cycle. Cycles repeat every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsy and CT, MRI, or PET/CT throughout the trial. Additionally, patients undergo blood sample collection on study. After completion of study treatment, patients are followed up at 30 days and then every 3 months for 2 years.

Conditions

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo tumor biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
BIOLOGICAL	Cemiplimab	Given IV
PROCEDURE	Computed Tomography	Undergo CT or PET/CT
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
DRUG	Pidnarulex	Given IV
PROCEDURE	Positron Emission Tomography	Undergo PET/CT

Timeline

Start date: 2026-12-21
Primary completion: 2027-09-30
Completion: 2027-09-30
First posted: 2025-08-29
Last updated: 2026-04-13

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT07147231. Inclusion in this directory is not an endorsement.