Actively Recruiting
A Phase 1 and Randomized Phase 2 Trial of Pidnarulex (CX-5461) and Cemiplimab (REGN2810) in Refractory Microsatellite Stable Colorectal Cancer
Led by National Cancer Institute (NCI) · Updated on 2026-05-13
86
Participants Needed
1
Research Sites
N/A
Total Duration
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AI-Summary
What this Trial Is About
Researchers are studying the treatment of patients with microsatellite stable (MSS) colorectal cancer that does not respond to standard therapies. The trial aims to find the best dose and evaluate the safety and effects of pidnarulex combined with cemiplimab, an immunotherapy drug, in these patients. This phase I/II trial also explores how the drugs affect tumor growth and the immune system's ability to fight cancer. In the first phase, patients receive cemiplimab intravenously on days 1 and 15, and pidnarulex intravenously on days 1 and 8 of each 28-day cycle, for up to 26 cycles if no disease progression or unacceptable side effects occur. In the second phase, patients are randomly assigned to receive either pidnarulex alone on days 1 and 8 every 28 days, or the combination of cemiplimab and pidnarulex on the same schedule. Throughout the trial, patients undergo tumor biopsies, blood sample collections, and imaging scans such as CT, MRI, or PET/CT. Participants will be monitored closely with regular blood tests, imaging, and biopsies to assess tumor response and side effects. Researchers will measure progression-free survival and other outcomes like response rates and overall survival up to two years. After treatment ends, patients have follow-up visits at 30 days and then every three months for two years to track long-term effects and health status.
CONDITIONS
Brief Title
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
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patients must have pathologically confirmed colorectal adenocarcinoma that is unresectable and/or metastatic and for which standard curative or palliative measures do not exist or are no longer effective
- Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- Patients must have pathologically confirmed proficient mismatch repair proteins (pMMR) and/or non-microsatellite-high status (non-MSI-H)
- Phase 2 patients must have at least one liver metastasis at study entry
- Phase 2 patients must have tumor molecular testing showing MYC amplification or deleterious FBXW7 mutation
- Phase 2 patients must have at least one tumor lesion amenable to biopsy
- Patients must undergo a 28-day washout for epidermal growth factor receptor (EGFR) inhibitors
- Patients must have progressed on or be intolerant to standard treatments including fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and EGFR inhibitors
- Age 18 years or older
- Eastern Cooperative Oncology Group (ECOG) performance status 2 or less
- Adequate blood counts and organ function as specified
- HIV patients on effective therapy with undetectable viral load are eligible
- Patients with treated brain metastases with no progression for at least 1 month
- Patients with certain prior or concurrent malignancies without interference to study
- Patients with cardiac function class II or better
- Agreement to use effective contraception or abstinence during and after study participation
- Ability and willingness to sign informed consent
You will not qualify if you...
- Active autoimmune diseases requiring systemic treatment in past 2 years
- Prior treatment with RNA polymerase inhibitors, G quadruplex stabilizers, or immunotherapy including PD-1/PD-L1 inhibitors
- Known photosensitivity disorders or unwillingness to use sun protection
- History of cicatricial conjunctivitis or active ocular surface disease
- Unresolved side effects greater than grade 1 from prior anticancer therapy except alopecia
- Receiving other investigational agents
- History of allergic reactions to pidnarulex or cemiplimab
- Use of strong CYP3A4 inhibitors or inducers
- Taking corticosteroids above 10 mg prednisone daily or other immunosuppressive agents
- Uncontrolled illnesses or conditions making participation hazardous
- Pregnant or lactating women due to potential fetal risk
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 26 cycles of 28 days each
Participants receive intravenous pidnarulex and/or cemiplimab according to their assigned phase and treatment arm. Treatment cycles repeat every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Participants undergo blood sample collection, tumor biopsy (in Phase 2), and imaging scans throughout the treatment period.
2 infusions per cycle; imaging and blood sample collection throughout treatment; tumor biopsy in Phase 2 arms
Duration - 30 days then every 3 months for 2 years
After completing treatment, participants are followed up to monitor health status and any late effects of the treatment.
1 visit at 30 days post-treatment, then visits every 3 months for 2 years
Trial Site Locations
Total: 1 location
1
JHU Sidney Kimmel Comprehensive Cancer Center LAO
Baltimore, Maryland, United States, 21231
Actively Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
3
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