Solid TumorPhase 1NCT07404332
5-Azacitidine Plus PD-1/PD-L1 Inhibitor With PD-1/PD-L1 Refractory Tumors
A Phase 1 study testing 5 Azacytidine, Pembrolizumab and Nivolumab in people with Solid Tumor and Locally Advanced Solid Tumor, run by Mohammed Milhem at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Solid Tumor, Locally Advanced Solid Tumor, Metastatic Tumor
- What is being tested?
- 5 Azacytidine, Pembrolizumab and Nivolumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Feb 2026to 28 Feb 2031
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- Patients may have previously received ipilimumab but must have relapsed or progressed while on therapy.
- Patients must have adequate archival tissue available for the purpose of downstream methylation status assessment, immunohistochemistry, RNA expression (10 slides at 5µM). If archival tissue is not available, a repeat biopsy is required.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Iowa Health Care
Iowa City, Iowa, 52242
Mohammed Milhem, MD, +1 319 356 2324, mohammed-milhem@uiowa.edu
Milhem
About this study
Official title: Phase I Study of 5-Azacitidine Plus PD-1/PD-L1 Inhibitor in Patients With PD-1/PD-L1 Refractory Tumors
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.
Read the detailed description
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.
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.
- Conditions
- Solid Tumor, Locally Advanced Solid Tumor, Metastatic Tumor
- Being tested
- 5 Azacytidine, Pembrolizumab, Nivolumab, Cemiplimab
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5 AzacytidineDrug
5-Azacitidine (Azacitidine) is a nucleoside analogue chemotherapy drug
PembrolizumabDrug
Pembrolizumab is a high-affinity humanized monoclonal antibody that functions as immune checkpoint inhibitor
NivolumabDrug
Nivolumab is a high-affinity humanized monoclonal antibody that functions as immune checkpoint inhibitor
CemiplimabDrug
Cemiplimab is a high-affinity humanized monoclonal antibody that functions as immune checkpoint inhibitor
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: 5 Azacytidine; Drug: Pembrolizumab; Drug: Nivolumab; Drug: Cemiplimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Treatment initiation through 30 days +/- 7 days post completion of therapy
Secondary outcomes (4)
Proportion of participants with a complete response (CR)
The proportion of patients with a pathologic complete response, defined as disappearance of all target lesions, disappearance of all non-target lesions and normalization of tumor marker level
Measured: Treatment initiation through five years
Proportion of participants with a partial response (PR)
At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD
Measured: Treatment initiation through five years
Overall Survival (OS)
Time from study treatment initiation to death due to any cause
Measured: Treatment initiation through five years
Progression Free Survival (PFS)
Time from study treatment initiation to disease progression or death due to any cause
Measured: Treatment initiation through five years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2026
- Study start11 Feb 2026
- Primary completion28 Feb 2028 (estimated)
- Study completion28 Feb 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mohammed Milhem
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Mohammed Milhem, University of Iowa
- Investigators
- Mohammed Milhem, MD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07404332
- Sponsor's protocol ID
- 202511023
- Status last verified
- May 2026
- First submitted
- 4 Feb 2026
- Last updated
- 28 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of 5-Azacitidine Plus PD-1/PD-L1 Inhibitor in Patients With PD-1/PD-L1 Refractory Tumors
- ClinicalTrials.gov ID
- NCT07404332
- Acronym / sponsor ID
- 202511023
- Conditions
- Solid Tumor, Locally Advanced Solid Tumor, Metastatic Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Mohammed MilhemUniversity, hospital or other
- Study start
- 11 Feb 2026 (actual)
- Primary completion
- 28 Feb 2028 (estimated)
- Study completion
- 28 Feb 2031 (estimated)
- First posted
- 11 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 5-Azacitidine Plus PD-1/PD-L1 inhibitor | Experimental | Drug: 5 Azacytidine, Drug: Pembrolizumab, Drug: Nivolumab, Drug: CemiplimabThis 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. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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).
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 5 Azacytidine5-Azacitidine (Azacitidine) is a nucleoside analogue chemotherapy drug | Drug | 5-Azacitidine Plus PD-1/PD-L1 inhibitor |
| PembrolizumabPembrolizumab is a high-affinity humanized monoclonal antibody that functions as immune checkpoint inhibitor | Drug | 5-Azacitidine Plus PD-1/PD-L1 inhibitor |
| NivolumabNivolumab is a high-affinity humanized monoclonal antibody that functions as immune checkpoint inhibitor | Drug | 5-Azacitidine Plus PD-1/PD-L1 inhibitor |
| CemiplimabCemiplimab is a high-affinity humanized monoclonal antibody that functions as immune checkpoint inhibitor | Drug | 5-Azacitidine Plus PD-1/PD-L1 inhibitor |
Primary outcome
Incidence of dose-limiting toxicities and responses as defined by CTCAE v5.0
Time frame: Treatment initiation through 30 days +/- 7 days post completion of therapy
Assess the safety and tolerability of 5-Azacitidine Plus PD-1/PD-L1 inhibitor
4 secondary outcomes
Proportion of participants with a complete response (CR)
Time frame: Treatment initiation through five years
Proportion of participants with a partial response (PR)
Time frame: Treatment initiation through five years
Overall Survival (OS)
Time frame: Treatment initiation through five years
Progression Free Survival (PFS)
Time frame: Treatment initiation through five years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mohammed Milhem, MD principal investigator
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 5 Azacytidine, Pembrolizumab and Nivolumab in people with Solid Tumor and Locally Advanced Solid Tumor, run by Mohammed Milhem at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mohammed Milhem, MD (+1 319 356 2324, mohammed-milhem@uiowa.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose-limiting toxicities and responses as defined by CTCAE v5.0 (time frame: Treatment initiation through 30 days +/- 7 days post completion of therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2026.