CAR T-Cell Therapy for Lung Cancer

Overseen By Caroline Babinec

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: UNC Lineberger Comprehensive Cancer Center

Disqualifiers: Less than 12 weeks expectancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 4 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with advanced lung cancer who have not responded well to certain standard therapies. The treatment modifies a person's own immune cells, specifically T cells, to better target and attack cancer cells, a method known as CAR T-cell therapy. The main goal is to determine the safety of this treatment and the maximum dosage that can be administered without causing excessive side effects. Individuals with lung cancer who have already tried platinum-based chemotherapy and PD-1/PD-L1 therapies, without success, might be suitable candidates for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking systemic corticosteroids at doses less than 10 mg of prednisone daily, you may still be eligible to participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that scientists are studying the safety of using specially modified immune cells to treat lung cancer. These cells, called iC9.GD2.CAR.IL-15 T cells, combine antibodies and T cells, both of which help the immune system fight diseases. While antibodies and T cells have been used separately to combat cancer, this study combines them for a potentially stronger effect.

Previous studies have shown that treatments with similar modified T cells can be well-tolerated by patients. However, since the iC9.GD2.CAR.IL-15 T cell therapy remains experimental, researchers are testing it to fully understand its safety. The study aims to find a dose that is safe and causes minimal side effects. As this is an early-stage trial, the main goal is to learn about the treatment's safety and any possible side effects.

Prospective participants can be assured that the therapy is closely monitored to ensure safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for lung cancer, which often include chemotherapy, radiation, and PD-1 or PD-L1 inhibitors, the iC9.GD2.CAR.IL-15 T-cell therapy takes a novel approach by reprogramming a patient’s own immune cells to specifically target cancer cells. This therapy is unique because it uses genetically modified T-cells to hunt and destroy cancer cells, potentially offering a more precise attack on the tumor. Researchers are excited about this treatment because it includes an innovative mechanism: the addition of IL-15, which could enhance the persistence and effectiveness of the T-cells, possibly leading to better outcomes for patients with advanced lung cancer that has become resistant to traditional treatments.

What evidence suggests that iC9.GD2.CAR.IL-15 T cells might be an effective treatment for lung cancer?

Research shows that the iC9.GD2.CAR.IL-15 T cells therapy, which participants in this trial will receive, could be a promising way to treat lung cancer. This treatment modifies a patient's own T cells to enhance their ability to attack cancer cells. It specifically targets the GD2 antigen, often found on cancer cells, including those in lung cancer. Early studies suggest that GD2 is an effective target for this therapy. By combining T cells with antibodies, the treatment aims to strengthen the immune system's ability to fight cancer. Although still experimental, these early results support further research into its potential effectiveness. ^{1 2 4 6 7}

Who Is on the Research Team?

Jared Weiss

Principal Investigator

[e-mail]

Are You a Good Fit for This Trial?

This trial is for adults with advanced lung cancer that's resistant to platinum chemotherapy and has been treated with PD-1/PD-L1 inhibitors. Participants must be in good enough health, have a life expectancy of at least 12 weeks, and women able to have children need a negative pregnancy test before cell collection.

Inclusion Criteria

My organs are functioning well.

I am taking less than 10 mg of prednisone daily or its equivalent.

I am resistant to platinum-based cancer treatment and have been treated with a PD1/PDL1 inhibitor. I am currently on low-dose steroids or none at all.

Exclusion Criteria

You are expected to live for less than 12 weeks.

My organs are not functioning properly.

I have not had platinum-based chemotherapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

T Cell Preparation

Blood is collected from subjects to prepare the iC9-GD2.CAR.IL-15 T cells. T cells are isolated and modified.

2-4 weeks

Treatment

Administration of iC9-GD2.CAR.IL-15 T cells to subjects.

Up to 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events, cytokine release syndrome, and neurotoxicity.

4 weeks

Long-term Follow-up

Monitoring of progression-free survival, overall survival, and duration of response.

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• iC9.GD2.CAR.IL-15 T cells

Trial Overview The study tests autologous T lymphocyte chimeric antigen receptor cells targeting GD2 (iC9.GD2.CAR.IL-15 T cells). It aims to find the safe dosage levels of these modified immune cells designed to fight lung cancer more effectively than antibodies or T cells alone.

How Is the Trial Designed?

Group I: iC9.GD2.CAR.IL-15 T Therapy Experimental Treatment 1 Intervention

Experimental: Single Arm Subjects with extensive stage lung cancer or stage IV non-small cell lung cancer that is platinum-refractory and received PD-1 and/or PD-L1 therapy will receive iC9.GD2.CAR.IL-15 T cells were manufactured from their collected blood sample.

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Bellicum Pharmaceuticals

Industry Sponsor

Trials

28

Recruited

1,400+

Published Research Related to This Trial

IL-15 modification significantly enhances the expansion, survival, and antitumor activity of CLDN18.2-targeting CAR-T cells in murine models, leading to improved tumor suppression compared to standard CAR-T cells.

In vivo studies showed that IL-15-expressing CAR-T cells not only infiltrated tumors more effectively but also provided a survival advantage in certain tumor models, highlighting their potential for clinical evaluation in patients with CLDN18.2-positive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-15 armoring enhances the antitumor efficacy of claudin 18.2-targeting CAR-T cells in syngeneic mouse tumor models. Shi, H., Li, A., Dai, Z., et al.[2023]

CAR-T cells engineered to overexpress IL-15 showed improved viability and anti-tumor effects, but also led to serious liver injuries and lower survival rates in mouse models, indicating potential toxicity issues.

Combining IL-15 with IL-15 receptor alpha (IL-15Ra) in CAR-T cells reduced cytokine release and improved mouse survival while still effectively inhibiting tumor growth, suggesting a way to enhance the safety and efficacy of CAR-T therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Co-expression IL-15 receptor alpha with IL-15 reduces toxicity via limiting IL-15 systemic exposure during CAR-T immunotherapy. Zhang, Y., Zhuang, Q., Wang, F., et al.[2022]

CAR-T cell therapy has shown remarkable success in treating blood cancers, but its effectiveness against solid tumors is limited due to the immunosuppressive environment of these tumors.

There is a pressing need for the development of next-generation personalized CAR-T cells targeting solid tumors, focusing on improving their efficacy, survival, persistence, and safety, particularly in lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cells for the Treatment of Lung Cancer. Chocarro, L., Arasanz, H., Fernández-Rubio, L., et al.[2022]

The second-generation GD3-specific chimeric antigen receptor (CAR) T cells, which include a CD28 costimulation domain, demonstrated improved antitumor activity, including better cytokine secretion and cytotoxicity, compared to first-generation CAR T cells.

In a mouse model of established GD3+ melanoma, the combination of these second-generation CAR T cells with systemic interleukin-2 (IL2) led to a 50% complete remission rate, highlighting the importance of IL2 for enhancing the efficacy of designer T-cell therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-GD3 chimeric sFv-CD28/T-cell receptor zeta designer T cells for treatment of metastatic melanoma and other neuroectodermal tumors. Lo, AS., Ma, Q., Liu, DL., et al.[2017]

CAR T-cell therapy, which involves engineering a patient's T cells to target cancer cells, has shown impressive success in treating leukemia and lymphoma, particularly with the CD19 target.

Research is ongoing to adapt CAR T-cell therapy for solid tumors like lung cancer and esophageal cancer, but there are significant challenges that need to be addressed to improve its effectiveness in these types of cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor (CAR) T-Cell Therapy for Thoracic Malignancies. Kiesgen, S., Chicaybam, L., Chintala, NK., et al.[2022]

Interleukin 15 (IL-15) enhances the effectiveness of cell-based cancer immunotherapies, such as CAR T and NK cell therapies, by boosting T and NK cell immune responses and supporting the persistence of CD8+ memory T cells.

IL-15 not only improves long-term anti-tumor immunity by preventing T cell death but also presents both advantages and challenges in its integration into current immunotherapy strategies, highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin 15 in Cell-Based Cancer Immunotherapy. Zhou, Y., Husman, T., Cen, X., et al.[2022]

Infusion of GD2-specific fourth-generation safety-designed chimeric antigen receptor (4SCAR)-T cells in eight patients with GD2-positive glioblastoma (GBM) was found to be safe and well tolerated, with no severe adverse events reported.

Of the eight patients, four experienced a partial response lasting between 3 to 24 months, indicating that 4SCAR-T cells can exert anti-GBM activity, with a median overall survival of 10 months post-infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of GD2-Specific 4SCAR-T cells in patients with glioblastoma. Liu, Z., Zhou, J., Yang, X., et al.[2023]

CAR-T cell therapy is a promising new immunotherapy that has shown success against both blood cancers and solid tumors, despite facing challenges in treating thoracic malignancies.

Key issues affecting CAR-T cell effectiveness include the lack of specific tumor antigens and an immunosuppressive environment, but ongoing research aims to address these challenges and improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor (CAR)-T Cell Immunotherapy Against Thoracic Malignancies: Challenges and Opportunities. Chen, L., Chen, F., Niu, H., et al.[2022]

In a phase 1 trial involving 12 children with neuroblastoma, GD2-CAR.15 NKTs were found to be safe, with no dose-limiting toxicities and only one case of mild cytokine release syndrome that was manageable with treatment.

The treatment showed an objective response rate of 25%, including one complete response, suggesting that GD2-CAR.15 NKTs can effectively target neuroblastoma, and their anti-tumor activity may be further improved by targeting the BTG1 protein.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-GD2 CAR-NKT cells in relapsed or refractory neuroblastoma: updated phase 1 trial interim results. Heczey, A., Xu, X., Courtney, AN., et al.[2023]

Murine GD2 CAR-T cells can cause severe neurotoxicity, which is influenced by the costimulatory domain used, highlighting the need for careful evaluation of CAR designs in preclinical models.

The newly developed SynNotch gated CAR-T, GD2-B7H3, shows improved efficacy and specificity against neuroblastoma in mouse models, benefiting from enhanced metabolic fitness and reduced exhaustion compared to traditional CAR-T cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical assessment of the efficacy and specificity of GD2-B7H3 SynNotch CAR-T in metastatic neuroblastoma. Moghimi, B., Muthugounder, S., Jambon, S., et al.[2021]

Interleukin-15 (IL-15) is a promising cytokine in cancer immunotherapy that enhances the immune response by activating natural killer (NK) cells, natural killer T (NKT) cells, and memory CD8+ T cells, potentially leading to the destruction of cancer cells in the tumor microenvironment.

IL-15-based therapies, including CAR T and CAR NK cell treatments, show encouraging results in preclinical and early clinical trials, suggesting that they could be effectively combined with other therapies like checkpoint inhibitors for improved cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological effects of IL-15 on immune cells and its potential for the treatment of cancer. Zhang, S., Zhao, J., Bai, X., et al.[2021]

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-04525

Genetically Modified Immune Cells for Cancer Treatment Genetically Modified Immune Cells (iC9-GD2.CAR.IL-15 T Cells) for the Treatment of Extensive Stage Small Cell Lung Cancer or Stage IV Non-small Cell Lung Cancer.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05620342

Autologous CAR T-Cells Targeting the GD2 Antigen for ... The purpose of this study is to test the safety of using a new treatment called autologous T lymphocyte chimeric antigen receptor cells against the GD2 antigen ...

3. trialx.com trialx.com/clinical-trials/listings/221988/autologous-car-t-cells-targeting-the-gd2-antigen-for-lung-cancer/?&radius=50

Autologous CAR T-Cells Targeting the GD2 Antigen for Lung ... The short name for this treatment is iC9.GD2.CAR.IL-15 T cells therapy is an experimental therapy and has not been approved by the Food and Drug Administration.

4. unclineberger.org unclineberger.org/cellular-immunotherapy/clinical-trials/

Clinical Trials - Adult and Pediatric Trials The purpose of this study is to test the safety of using a new treatment called autologous T lymphocyte chimeric antigen receptor cells against the GD2 antigen ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8756261/

Targeting GD2 with CAR T cells in lung cancer GD2 is a promising target for CAR-T cell therapy in lung cancer. Tazemetostat treatment could be used to upregulate GD2 expression in tumor cells, enhancing ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05620342/autologous-car-t-cells-targeting-the-gd2-antigen-for-lung-cancer

Autologous CAR T-Cells Targeting the GD2 Antigen for Lung ... The purpose of this study is to test the safety of using a new treatment called autologous T lymphocyte chimeric antigen receptor cells against the GD2 antigen ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03721068

NCT03721068 | Study of CAR T-Cells Targeting the GD2 ... This multicenter study is designed to combine both T cells and antibodies in order to create a more effective treatment. The treatment that is being researched ...