Actively Recruiting
Phase I Study of 5-Azacitidine Plus PD-1/PD-L1 Inhibitor in Patients With PD-1/PD-L1 Refractory Tumors
Led by Mohammed Milhem · Updated on 2026-05-28
35
Participants Needed
1
Research Sites
156 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the best biological dose of 5-Azacitidine combined with PD-1/PD-L1 inhibitors in patients whose tumors no longer respond to these immunotherapies. This Phase I study focuses on patients with locally advanced or metastatic solid tumors where PD-1 or PD-L1 treatments have already been approved. The goal is to find an optimal dose to improve treatment options for these resistant tumors. The study tests six different doses of 5-Azacitidine ranging from 5 to 75 mg/m2, given together with a PD-1/PD-L1 inhibitor such as Pembrolizumab, Nivolumab, or Cemiplimab. The PD-1/PD-L1 inhibitors are administered at standard FDA-approved doses for this purpose. Participants receive these treatments according to the assigned dose group during the study. Participants will be monitored for side effects and tumor response using clinical and laboratory assessments, including imaging scans and blood tests. The main outcome is to measure dose-limiting toxicities and treatment responses within about one month after therapy. Longer-term outcomes like survival and tumor progression will be followed for up to five years. This process helps researchers understand the safety and effects of the drug combination over time.
CONDITIONS
Brief Title
5-Azacitidine Plus PD-1/PD-L1 Inhibitor With PD-1/PD-L1 Refractory Tumors
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Provided written and voluntary informed consent
- At least 18 years of age or older
- Histologically and radiologically confirmed locally advanced or metastatic unresectable solid tumor malignancy approved for PD-1 or PD-L1 therapy
- At least one target lesion measurable by RECIST 1.1 criteria
- ECOG performance status of 0, 1, or 2
- Documented progression on PD-1 or PD-L1 inhibitors
- Recovery from prior therapy toxicity to grade 1
- Adequate renal function (creatinine clearance >15 mL/min/1.73 m2 or normal creatinine level)
- Adequate liver function (AST/ALT <3x normal or <5x with liver metastasis; total bilirubin ≤1.5x normal)
- Adequate blood counts (ANC ≥1.0 x 10^9/L, platelets ≥100 x 10^9/L, hemoglobin ≥7.0 g/dL)
- Use of effective contraception during and 6 months after treatment if of childbearing potential
- Prior hypomethylating agent allowed if not combined with ipilimumab
- Prior ipilimumab allowed if relapsed or progressed
- Adequate archival tissue available or willing to undergo repeat biopsy
You will not qualify if you...
- Prior or concurrent malignancy interfering with safety or efficacy assessment
- Active, untreated central nervous system metastases
- Pregnancy or breastfeeding
- Active infection
- Significant impairment of blood, liver, or kidney function
- Current or recent use of systemic steroids or history of long-term steroid use
- History of inflammatory bowel disease or symptomatic autoimmune disease
- Major surgery or significant injury within 28 days before enrollment
- Chemotherapy, immunosuppressive agents, or investigational drugs within 28 days before study start
- Any medical condition making study drug administration hazardous or affecting interpretation of adverse events
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 - Repeated cycles until disease progression or discontinuation
Participants receive 5-Azacitidine in combination with a PD-1/PD-L1 inhibitor at standard dosing to assess the optimal biological dose.
Multiple visits depending on treatment cycles
Duration - Up to 5 years
Participants are monitored for safety and treatment responses after completing therapy.
Periodic follow-up visits for up to 5 years
Trial Site Locations
Total: 1 location
1
University of Iowa Health Care
Iowa City, Iowa, United States, 52242
Actively Recruiting
Research Team
M
Mohammed Milhem, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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