5-Azacitidine Plus PD-1/PD-L1 Inhibitor With PD-1/PD-L1 Refractory Tumors

NCT07404332 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202511023
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I study to determine the optimal biological dose (OBD) of 5-Azacitidine in combination with PD-1/PD-L1 inhibitors in patients with tumors refractory to PD-1/PD-L1 inhibitors, for which such treatments have been approved.

Conditions

Solid Tumor; Locally Advanced Solid Tumor; Metastatic Tumor

Outcome Measures

Primary Outcomes (1)

• Incidence of dose-limiting toxicities and responses as defined by CTCAE v5.0

  Assess the safety and tolerability of 5-Azacitidine Plus PD-1/PD-L1 inhibitor

  Treatment initiation through 30 days +/- 7 days post completion of therapy

Secondary Outcomes (4)

• Proportion of participants with a complete response (CR)

  Treatment initiation through five years

• Proportion of participants with a partial response (PR)

  Treatment initiation through five years

• Overall Survival (OS)

  Treatment initiation through five years

• Progression Free Survival (PFS)

  Treatment initiation through five years

Study Arms (1)

5-Azacitidine Plus PD-1/PD-L1 inhibitor

EXPERIMENTAL

This Phase I study will assess 6 doses of 5-Azacitidine (5, 10, 15, 25, 50 and 75 mg/m2) in combination with a PD1/PD-L1 inhibitor. The PD1/PD-L1 inhibitor will be given at standard of care dosing approved by the FDA for this indication. Inhibitors approved for study indications include Pembrolizumab, Nivolumab, and Cemiplimab.

Drug: 5 Azacytidine; Drug: Pembrolizumab; Drug: Nivolumab; Drug: Cemiplimab

Interventions

5 Azacytidine DRUG

5-Azacitidine (Azacitidine) is a nucleoside analogue chemotherapy drug

5-Azacitidine Plus PD-1/PD-L1 inhibitor

Pembrolizumab DRUG

Pembrolizumab is a high-affinity humanized monoclonal antibody that functions as immune checkpoint inhibitor

5-Azacitidine Plus PD-1/PD-L1 inhibitor

Nivolumab DRUG

Nivolumab is a high-affinity humanized monoclonal antibody that functions as immune checkpoint inhibitor

5-Azacitidine Plus PD-1/PD-L1 inhibitor

Cemiplimab DRUG

Cemiplimab is a high-affinity humanized monoclonal antibody that functions as immune checkpoint inhibitor

5-Azacitidine Plus PD-1/PD-L1 inhibitor

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 for which PD-1 or PD-L1 therapy is already approved by the FDA. Locally advanced is defined as unresectable in the opinion of the treating physician. A repeat biopsy is required if previous biopsy tissue is unavailable.
• At least one Response Evaluation Criteria in Solid Tumors (RECIST 1.1) - defined target lesion.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 (fully active, able to carry on all pre-disease performance without restriction), 1 (restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, such as light housework or office work), or 2 (ambulatory and capable of self-care but unable to carry out any work activities, spending more than 50% of waking hours up and about).
• Documented progression on PD1 or PD-L1 inhibitors.
• Recovery from any acute toxicity associated with prior therapy to grade 1.
• Renal function (creatinine level within normal institutional limit, or creatinine clearance \>15 mL/min/1.73 m2 for patients with creatinine levels above institutional normal, calculated using the Cockcroft-Gault formula).
• Liver function (AST/ALT \<3.0 X institutional upper limit of normal OR \<5 X institutional upper limit of normal in cases of liver metastasis; total bilirubin ≤ 1.5 times upper limit of normal).
• Adequate hematological lab values including:
• Absolute Neutrophil Count (ANC) ≥ 1.0 X 109/L
• Platelets ≥ 100X109/L
• Hemoglobin ≥ 7.0 g/dL
• Female subjects of childbearing potential and non-sterilized male subjects who intend to be sexually active during the study must agree to use a highly effective method of contraception from time of screening, throughout the whole duration of the drug treatment, and during the 6-month post-treatment washout period.
• Patients may have previously received a hypomethylating agent, as long as it was not given in combination with ipilimumab.

You may not qualify if:

• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
• Patients with active, untreated metastases in the central nervous system.
• Patients who are pregnant or breastfeeding.
• Patients who have an active infection.
• Patients with significant hematologic, hepatic, and renal function impairment.
• Patients who are being treated for any concurrent medical condition requiring the use of systemic steroids or history of long-term use of systemic steroids.
• Patients who have a history of inflammatory bowel disease or a history of symptomatic autoimmune disease.
• Patients who have had any major surgical procedure or significant traumatic injury within 28 days prior to study enrollment.
• Patients who have received chemotherapy, immunosuppressive agents or any investigational drug within 28 days prior to starting the study drugs.
• Patients who have any underlying medical condition which, in the treating physician's opinion, will make the administration of study drugs hazardous or obscure the interpretation of adverse events.

Sponsors & Collaborators

• Mohammed Milhem: lead

Study Sites (1)

University of Iowa Health Care

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Azacitidine; pembrolizumab; Nivolumab; cemiplimab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Mohammed Milhem, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mohammed Milhem, MD

CONTACT

+1 319 356 2324; mohammed-milhem@uiowa.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: February 4, 2026
• First Posted: February 11, 2026
• Study Start: February 28, 2026
• Primary Completion (Estimated): February 28, 2028
• Study Completion (Estimated): February 28, 2031
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)