IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors

NCT07672483 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10002091002091-C
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Myeloid cells are a type of immune cell found in most tumors. Interleukin 12 (IL-12) is a protein that helps the immune system kill tumor cells. Researchers want to know if myeloid cells that have been genetically engineered to produce IL-12 (IL-12 GEMys) can activate the immune system to attack cancer cells in solid tumors. Objective: To test IL-12 GEMys in people with cancer. Eligibility People aged 18 years and older with cancer that returned or failed to respond to treatment. Design: Participants will be screened. They will have a physical exam with blood tests. They will have tests of their heart and lung function. They will have imaging scans of their tumors. A sample of tumor tissue may be taken. Participants will have daily injections for few days to prepare them to undergo leukapheresis: Blood will be taken from the body through a needle inserted into a vein. The blood will pass through a machine that separates out stem cells. The remaining blood will be returned to the body through a different needle. The collected stem cells will be modified in a lab to create IL-12 GEMys. Participants will check in to the hospital. They will receive drugs for 5 days to prepare their body for the treatment. Then they will have their own IL-12 GEMys infused through a needle inserted into a vein. They will stay in the hospital until they are well enough to go home. This may be 7 to 14 days or longer. Some participants may receive a second treatment with IL-12 GEMys within 2 years after the first. Participants will have follow-up visits for about 5 years. These will include imaging scans and blood tests. ...

Conditions

Refractory Solid Tumor Malignancies; Relapsed Solid Tumor Malignancies

Keywords

GEMys; Cd34+ Cells; Lymphodepletion; IFNy; Leukapheresis

Outcome Measures

Primary Outcomes (2)

• Part A (Escalation): Determine the recommended phase 2 dose (RP2D) of IL-12

  Maximum dosage of GEMys IL-12 with which no more than 1 participant experience dose limiting toxicity as assessed by grade of adverse event

  0-28 Days

• Part B (Expansion): Assess whether IL-12 or IFNy levels, or both increase in tumors post treatment at the RP2D

  Increased IL-12 and/or IFNy levels and IL-12 production as measured by ELISA, using a paired t-test or Wilcoxon signed rank test

  1 week

Secondary Outcomes (4)

• Determine the feasibility of manufacturing IL-12 GEMys that express a truncated epidermal growth factor receptor (EGFRt) meeting release criteria

  Time of cell infusion

• Determine the safety of IL-12 GEMys

  0-12 months

• Assess the antitumor activity of IL-12 GEMys

  0-5 years

• Assess the re-treatment utility of IL-12 GEMys

  0-5 years

Study Arms (2)

Arm 1

EXPERIMENTAL

Escalating/de-escalating doses of IL-12 GEMys with or without conditioning (cyclophosphamide and fludarabine)

Biological: IL-12 GEMys; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Cetuximab

Arm 2

EXPERIMENTAL

RP2D of IL-12 GEMys with or without conditioning (cyclophosphamide and fludarabine)

Biological: IL-12 GEMys; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Cetuximab

Interventions

IL-12 GEMys BIOLOGICAL

Cell therapy generated from autologous CD34+ cells. Administered on Day 0 as an IV infusion not to exceed 20ml/kg or 40ml/kg depending on DMSO levels.

Arm 1; Arm 2

Cyclophosphamide DRUG

Lymphodepletive chemotherapy administered as 30 mg/kg IV infusion over 1 hour daily on days -6 and -5.

Arm 1; Arm 2

Fludarabine DRUG

Lymphodeleptive chemotherapy administered as 25 mg/m\^2 IV infusion over 30 minutes on days -6 through -2.

Arm 1; Arm 2

Cetuximab DRUG

Administered as IV infusion at 500 mg/m\^2, if needed.

Arm 1; Arm 2

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Relapsed or refractory solid tumor malignancies for whom standard measures do not exist or are no longer effective. Must have histologic confirmation of original diagnosis or relapse.
• Participants must have evaluable (measurable or not measurable) disease.
• Part B only: Participants must:
• be willing to undergo mandatory pre- and post-treatment tumor biopsies. Tumor tissue should either be taken from non-target lesions or from target lesions where sampling can be done without impacting lesion measurement
• and
• have disease amenable to biopsy to allow to perform pre- and post-tumor biopsies.
• Participants with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy and close monitoring for over 3 months shows no active progression.
• At least one prior cancer treatment when upfront standard therapy exists. Note: There is no limit to the number or type of prior treatment regimens.
• The indicated time must have elapsed since any systemic anti-cancer therapy prior to leukapheresis.
• Age \>= 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status \<= 2.
• Note: Participants who are unable to walk because of paralysis, but who are able to maintain supine position independently in a wheelchair, will be considered ambulatory for the purpose of performance status.
• Participants must have adequate organ and marrow function as defined below:
• Peripheral absolute neutrophil count (ANC) \>= 1000/mm\^3
• Platelet count \>= 100,000/mm\^3

You may not qualify if:

• Participants with history of primary CNS tumors or leptomeningeal disease.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide, fludarabine, IL-12, or other agents used in the study.
• Concurrent untreated opportunistic infections as evidenced by history, blood test or imaging at screening.
• Active systemic infections requiring anti-infective treatment.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease) or secondary/acquired immunodeficiency requiring steroids or other non-steroid immunosuppressive agents.
• History of clonal hematopoiesis of indeterminate potential (CHIP) or myelodysplasia/myelodysplastic syndrome (MDS) or monoclonal gammopathy of undetermined significance (MGUS).
• Participants with symptomatic pleural effusions requiring intervention or with recent history (within 3 months) of pleural effusions that required intervention.
• Participants with ischemic symptoms (may include chest pain/pressure, shortness of breath, nausea, vomiting, sweating, and/or pain in the neck, shoulder, jaw or arm) confirmed by stress test OR a history of coronary revascularization (unless the participant has a normal cardiac stress test after revascularization and within 12 months prior to leukapheresis).
• Any form of diagnosed autoimmune disease requiring immune suppression as well as participants with active autoimmune skin diseases such as psoriasis or any history of active systemic autoimmune disease (e.g., Crohn's, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression/systemic disease-modifying agents within the last 2 years. Exceptions will be allowed for vitiligo and hypothyroidism that has been stable on thyroid replacement medications for \> 6 weeks prior to leukapheresis.
• Any participant who developed autoimmunity (\>= grade 3 per CTCAE v. 6.0) with checkpoint inhibitor use. Note: Exceptions will be allowed for vitiligo and hypothyroidism that has been stable on thyroid replacement medications for \> 6 weeks prior to leukapheresis.
• Participants who have a major surgical procedure, other than for diagnosis, within 4 weeks prior to leukapheresis or anticipated to need a major surgical procedure during the study.
• History of prior solid organ transplantation.
• Participants that require urgent therapy due to tumor mass effects or spinal cord compression within 2 weeks prior to leukapheresis.
• Any investigational therapy within 2 weeks prior to leukapheresis.
• Pregnancy confirmed with Beta-human chorionic gonadotropin (Beta-HCG) serum or urine pregnancy test in WOCBP at screening. Note: In case of a suspected false-positive serum or urine test result, additional evaluation must be done to rule out pregnancy.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

Cyclophosphamide; fludarabine; Cetuximab

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Rosandra N Kaplan, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NCI POB Solid Tumor Referral Team

CONTACT

(240) 858-7013; ncipobstreferrals@mail.nih.gov

Rosandra N Kaplan, M.D.

CONTACT

(240) 760-6198; kaplanrn@mail.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2026
• First Posted: June 29, 2026
• Study Start (Estimated): August 5, 2026
• Primary Completion (Estimated): January 15, 2028
• Study Completion (Estimated): January 15, 2029
• Last Updated: July 31, 2026

Record last verified: 2026-07-28

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available as soon as possible or at the time of associated publication. Data not published in a manuscript will be shared via public source once the data set completes QC.
• Access Criteria: Clinical data will be made available upon request and with the permission of the study PI. Genomic data are made available via dbGAP through requests to the data custodians.

Locations

US (1)