AzTrials
AzTrials

Non Small Cell Lung CancerPhase 1/2NCT06219174

Targeting ODC as an Immunotherapeutic Target in STK11 (LKB1) Pathway-Deficient NSCLC (DFMO)

A Phase 1/2 study testing Pembrolizumab and Difluoromethylornithine in people with Non Small Cell Lung Cancer and Lung Cancer, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
Search all trials

Trial summary

The purpose of this study is to establish the safety, toxicity, and tolerability of Difluoromethylornithine (DFMO) in combination with pembrolizumab in advanced/metastatic Non-Small Cell Lung Cancer (NSCLC). Researchers also want to investigate how effective DFMO is at treating patients with advanced/ metastatic NSCLC. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non Small Cell Lung Cancer, Lung Cancer
What is being tested?
Pembrolizumab and Difluoromethylornithine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
1 siteUnited States
Study dates
7 Aug 2024to Aug 2029
Phase
Phase 1/2
Are there results?
None posted in the registry

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must be willing and able to provide written informed consent/assent for the trial.
  • Patients must be ≥ 18 years of age on day of signing informed consent.
  • Patients must have measurable disease based on RECIST 1.1
  • Patients must have archival tissue where available. Patients enrolled on the phase 1 escalation trial where archival tissue is not available will undergo a fresh biopsy where clinically feasible after discussion with the sponsor.
  • Patients enrolled on the Phase II trial must be willing and able to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion.
  • Tumor proportional score of PD-L1 ≥1%
Show all 16Show fewer
  • Patients must have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  • Patients must demonstrate adequate organ function on all screening labs. Screening labs should be performed within 10 days of treatment initiation.
  • Histologically confirmed NSCLC that is at advanced/metastatic stage and for which there is no standard therapy option likely to convey clinical benefit. Advanced/metastatic is defined as unresectable or metastatic disease. Patients must have exhausted all approved available therapies.
  • Patients must harbor an STK11 mutation via CLIA-certified assay.
  • Phase I: Maybe treatment naïve or pretreated for advance or metastatic NSCLC. Patients whose tumors harbor an activating mutation (including but not limited to EGFR, ALK, ROS1) are eligible if they were previously treated with targeted therapy.
  • Phase II: Patients must be treatment naïve in the stage IV setting, with the exception of patients whose tumors harbor an activating mutation (including but not limited to EGFR, ALK, ROS1) and were previously treated with targeted therapy.
  • Female patients of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication.
  • Female patients of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication.
  • Male patients should agree to use an adequate method of barrier contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  • Patients cannot have clinically significant hearing loss that requires a hearing aid.

Who cannot join

  • Patients who are currently participating in and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
  • Patients that have a diagnosis of immunodeficiency or is receiving systemic steroid therapy at doses ≥ 10 mg prednisone or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  • Patients that have a known history of TB Disease (Mycobacterium tuberculosis).
  • Patients that have a hypersensitivity to pembrolizumab, DFMO or any of its excipients.
  • Patients enrolled on the phase II trial, who have had prior treatment with a PD1 or PDL1 inhibitor, anti-CTLA 4 antibody or any other antibody or drug that specifically targets immune checkpoint pathway in the stage IV setting (i.e. not "immune therapy naïve").
  • Patients who have received thoracic radiation >30Gy within six months of the first dose of pembrolizumab.
Show all 22Show fewer
  • Patients that had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Patients that have received major surgery must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Patients that have a known additional malignancy that is progressing or requires active treatment.
  • Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
  • Patients that have a known active central nervous system (CNS) metastasis and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they have stable CNS disease for at least 4 weeks prior to enrollment, have known treated and asymptomatic brain metastases and not using steroids in doses greater than 10 mg of prednisone daily (or equivalent). This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
  • Patients that have active autoimmune disease that has required systemic treatment in the past 2 years.
  • Patients that have an active infection requiring systemic therapy.
  • Patients that have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, that would substantially increase risk of incurring adverse events (AEs) from the study medications, that would interfere with the subject's participation for the full duration of the trial or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Patients that have a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial.
  • Patients that have a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Patients that have known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Patients that have received a live vaccine within 30 days of planned start of study therapy.
  • Patients that have a history of, or any evidence of active non-infectious pneumonitis that required or requires steriods.
  • Patients that have evidence of interstitial lung disease (ILD).
  • Patients that have a history of symptomatic (NYHA class II-IV) heart failure.
  • Patients harboring STK11 variants listed in ClinVAR as benign or likely-benign will be excluded from this study.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: Targeting ODC as an Immunotherapeutic Target in STK11 (LKB1) Pathway-Deficient NSCLC

The purpose of this study is to establish the safety, toxicity, and tolerability of Difluoromethylornithine (DFMO) in combination with pembrolizumab in advanced/metastatic Non-Small Cell Lung Cancer (NSCLC). Researchers also want to investigate how effective DFMO is at treating patients with advanced/ metastatic NSCLC.

Being tested
Pembrolizumab, Difluoromethylornithine
Keywords
Pembrolizumab, Difluoromethylornithine
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Also called Keytruda

    200 mg IV Q3 weeks

  • DifluoromethylornithineDrug

    Also called DFMO

    Dose Level -1: 4500 mg/m2 by mouth (PO) daily Dose Level 1: 6750 mg/m2 by mouth (PO) daily Dose Level 2: 9000 mg/m2 by mouth (PO) daily

Study groups in NCT06219174
Study groupRoleWhat they receive
Phase 1: Dose Escalation for Pembrolizumab and Difluoromethylornithine (DFMO)ExperimentalDifluoromethylornithine (DFMO) + Pembrolizumab Pre-treated or treatment naive advanced or metastatic NSCLC. The phase I dose escalation will include a fixed dose of Pembrolizumab IV every 3 weeks and escalating doses of DFMO (three dose levels) to determine the maximum tolerated dose (MTD) to be used in the phase II portion of the trial. DFMO level -1: Dose Level -1: 4500 mg/m2 by mouth (PO) once a day (QD). DFMO Level 1: (start): 6750 mg/m2 PO QD Dose Level 2: 9000 mg/m2 PO QD
Receives: Drug: Pembrolizumab; Drug: Difluoromethylornithine
Phase II: Pembrolizumab and Difluoromethylornithine (DFMO)Active comparatorDifluoromethylornithine (DFMO) + Pembrolizumab Advanced/metastatic NSCLC who are immunotherapy naïve. Pembrolizumab IV flat dose every 3 weeks DFMO dose to be determined (TBD) based on maximum tolerated dose (MTD) and dose limiting toxicities (DLT) in Phase I dose escalation.
Receives: Drug: Pembrolizumab; Drug: Difluoromethylornithine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I- Maximum Tolerated Dose (MTD)

    To determine the maximum tolerated dose (MTD) and recommended phase II dose (R2PD) of DFMO in combination with pembrolizumab. The MTD will be declared if 1 or fewer patients have a Dose limiting toxicity (DLT) in that dose level.

    Measured: Up to 12 Months

  2. Phase II- Objective Response Rate (ORR)

    To determine the efficacy of DFMO in combination with pembrolizumab. Objective response is defined as confirmed complete response (CR) or confirmed partial response (PR) based on modified RECIST guidelines version 1.1.

    Measured: Up to 5 Years

Secondary outcomes (2)

  1. Phase II- Progression Free Survival (PFS)

    Progression-free survival will be measured from the start of treatment with pembrolizumab and DFMO until the documentation of disease progression or death due to any cause, whichever occurs first. For subjects who are alive and progression-free at the time of data cut-off for analysis, PFS will be censored at the last tumor assessment date.

    Measured: Up to 5 Years

  2. Phase II- Overall Survival (OS)

    Overall survival will be determined as the time from the start of treatment with pembrolizumab and DFMO until death due to any cause. For subjects who are alive at the time of data cut-off, OS will be censored on the last date when subjects are known to be alive.

    Measured: Up to 5 Years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jan 2024
  2. Study start7 Aug 2024
  3. Primary completionAug 2029 (estimated)
  4. Study completionAug 2029 (estimated)

Why it stopped: Drugs unavailable

Resources

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
45 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06219174
Sponsor's protocol ID
MCC-20386
Status last verified
Mar 2026
First submitted
12 Jan 2024
Last updated
6 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Pembrolizumab and Difluoromethylornithine in people with Non Small Cell Lung Cancer and Lung Cancer, run by H. Lee Moffitt Cancer Center and Research Institute 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 16 inclusion and 22 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: paused, as of the sponsor's last update on 6 Mar 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I- Maximum Tolerated Dose (MTD) (time frame: Up to 12 Months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06219174.

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 6 Mar 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in