CAR T-Cell Therapy for Small Cell Lung Cancer

Recruiting in Palo Alto (17 mi)

+3 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Legend Biotech USA Inc

Must not be taking: Immunomodulatory treatments, High-dose steroids

Disqualifiers: Immunodeficiency, Brain metastasis, Autoimmune, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests specially modified immune cells in patients with advanced lung cancers. These immune cells are designed to find and destroy cancer cells by targeting a specific protein on them.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on treatments like cellular immunotherapy or certain immunomodulatory drugs, you may not be eligible to participate.

What data supports the effectiveness of the treatment LB2102 for small cell lung cancer?

Research shows that CAR T-cell therapies targeting DLL3, like LB2102, have shown promise in treating small cell lung cancer by effectively attacking cancer cells in models and enhancing immune response. Additionally, similar treatments have demonstrated safety and potential effectiveness in clinical settings, suggesting LB2102 could be a promising option.

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Is CAR T-Cell Therapy safe for small cell lung cancer?

AMG 119, a CAR T-Cell Therapy targeting DLL3 for small cell lung cancer, has been shown to be safe and well tolerated in clinical trials, with no dose-limiting toxicities reported.

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How is the CAR T-Cell Therapy LB2102 different from other treatments for small cell lung cancer?

The CAR T-Cell Therapy LB2102 is unique because it targets a specific protein called DLL3 found on small cell lung cancer cells and includes a component that releases IL-18, a substance that boosts the immune response, making it potentially more effective than traditional treatments.

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Eligibility Criteria

This trial is for adults with extensive stage small cell lung cancer or large cell neuroendocrine lung cancer who've had prior treatment but didn't respond well, can't tolerate further standard treatments, or chose not to continue them. They must be in relatively good health (ECOG status of 0 or 1), have a life expectancy of at least 4 months, and agree to use effective contraception.

Inclusion Criteria

My lung cancer cannot be removed by surgery and fits specific types.

I can provide a tissue sample of my tumor for the study.

I have enough non-mobilized cells available for treatment creation.

Exclusion Criteria

I have had or am preparing for a stem cell or organ transplant.

Plans to become pregnant or breastfeed, or father a child within 1 year after receiving a LB2102 infusion

My cancer has spread to the lining of my brain and spinal cord.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pretreatment

Preparation and baseline assessments before treatment initiation

1-2 weeks

Treatment

Dose escalation and cohort expansion with DLL3-directed CAR T-cells

28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

Post-Progression Follow-up

Monitoring of participants after disease progression

Minimum of 2 years

Participant Groups

The study is testing LB2102, a new type of therapy involving T-cells engineered to target DLL3 on cancer cells. It's an early-phase trial designed to find the right dose and assess how safe it is for patients with specific types of lung cancer.

Group I: Experimental LB2102 Experimental Treatment 1 Intervention

DLL3-Directed Chimeric Antigen Receptor T-cells (CAR T)

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Moffitt Cancer Center Tampa, FL

University of Kentucky - Markey Cancer Center Lexington, KY

Memorial Sloan Kettering Cancer Center New York, NY

Dana-Farber Cancer Institute Boston, MA

Who Is Running the Clinical Trial?

Legend Biotech USA Inc Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

IL-18-secreting CAR T cells targeting DLL3 are highly effective in small cell lung cancer models. [2023] Patients with small cell lung cancer (SCLC) generally have a poor prognosis and a median overall survival of only about 13 months, indicating the urgent need for novel therapies. Delta-like protein 3 (DLL3) has been identified as a tumor-specific cell surface marker on neuroendocrine cancers, including SCLC. In this study, we developed a chimeric antigen receptor (CAR) against DLL3 that displays antitumor efficacy in xenograft and murine SCLC models. CAR T cell expression of the proinflammatory cytokine IL-18 greatly enhanced the potency of DLL3-targeting CAR T cell therapy. In a murine metastatic SCLC model, IL-18 production increased the activation of both CAR T cells and endogenous tumor-infiltrating lymphocytes. We also observed an increased infiltration, repolarization, and activation of antigen-presenting cells. Additionally, human IL-18-secreting anti-DLL3 CAR T cells showed an increased memory phenotype, less exhaustion, and induced durable responses in multiple SCLC models, an effect that could be further enhanced with anti-PD-1 blockade. All together, these results define DLL3-targeting CAR T cells that produce IL-18 as a potentially promising novel strategy against DLL3-expressing solid tumors.

2. England pubmed.ncbi.nlm.nih.gov

Clinical Pharmacology Profile of AMG 119, the First Chimeric Antigen Receptor T (CAR-T) Cell Therapy Targeting Delta-Like Ligand 3 (DLL3), in Patients with Relapsed/Refractory Small Cell Lung Cancer (SCLC). [2023] With the promise of a potentially single-dose curative regimen, CAR-T cell therapies have brought a paradigm shift in the treatment and management of hematological malignancies with 6 approved products in the USA. However, there are no approved CAR-T cell therapies for solid tumors. Herein, we report the clinical pharmacology profile of AMG 119, the first CAR-T cell therapy targeting delta-like ligand 3 (DLL3), in patients with relapsed/refractory (R/R) small cell lung cancer (SCLC). AMG 119 demonstrated robust cellular expansion with long-lasting cell persistence and a favorable exposure-response relationship. AMG 119 has been demonstrated to be clinically safe and well tolerated at the doses tested, with no dose-limiting toxicities (DLTs) reported. This is the first publication of the clinical pharmacology profile of a CAR-T cell therapy in SCLC, with encouraging cellular kinetics data supporting the potential for CAR-T cell therapy in solid tumor space.

3. United States pubmed.ncbi.nlm.nih.gov

SCLC's Treatment Arsenal Improving. [2022] Although the treatment landscape for small cell lung cancer has hardly changed in decades, new possibilities are emerging. Long-term data from KEYNOTE-604 support incorporating immune checkpoint inhibition up front, as this provides durable benefit. A bispecific T-cell engager and other combination therapies also show signs of potential as second- or later-line therapies.

4. United States pubmed.ncbi.nlm.nih.gov

Treatment of limited small cell lung cancer: an old or new challenge? [2011] This review highlights how progress has been made in treating limited small cell lung cancer and outlines current challenges to overcome for improved cure rates.

5. England pubmed.ncbi.nlm.nih.gov

Cellular immunotherapy as maintenance therapy prolongs the survival of the patients with small cell lung cancer. [2018] Small cell lung cancer (SCLC) relapses rapidly after the initial response to chemotherapy and shows drug-resistance. This study was to investigate the efficacy and safety of cellular immunotherapy (CIT) with autologous natural killer (NK), γδT, and cytokine-induced killer (CIK) cells as maintenance therapy for SCLC patients.

6. England pubmed.ncbi.nlm.nih.gov

Phase I trial of the DLL3/CD3 bispecific T-cell engager BI 764532 in DLL3-positive small-cell lung cancer and neuroendocrine carcinomas. [2022] Poorly differentiated neuroendocrine carcinomas such as small-cell lung cancer (SCLC) have poor survival and high relapse rates. DLL3 is found on these carcinomas and has become a target of increasing interest in recent years. The bispecific DLL3/CD3 T-cell engager BI 764532 has been shown to induce complete tumor regression in a human T cell-engrafted mouse model. Here, we describe the study design of a first-in-human, phase I, multicenter, open-label, non-randomized, dose-escalation study in patients with SCLC or other DLL3-positive neuroendocrine carcinomas. The study will determine the maximum tolerated dose and evaluate safety, tolerability, pharmacokinetics and preliminary efficacy of BI 764532 monotherapy.

7. Italy pubmed.ncbi.nlm.nih.gov

The incidences of adverse events in small-cell lung cancer patients after radiotherapy and immunotherapy treatment: a systematic review and meta-analysis. [2022] Immunotherapy is important in treating small-cell lung cancer (SCLC), and its anti-tumor effects are better when combined with radiotherapy. However, the toxicity of this combination is little known. This study assessed the incidences of adverse events when adding radiotherapy to ICIs in patients with SCLC. We searched the online databases to identify eligible studies and included nine references. For extensive-stage SCLC patients, the median PFS ranged from 4.5 to 12.5 months, and median OS ranged from 8.4 to NR months, respectively. The incidences of grade 3 or higher pneumonitis, lung infection, diarrhea, and fatal adverse events were 8.7% (95% CI: 5%-14.7%), 6.7% (95% CI: 2.5%-16.5%), 12.6% (95% CI: 7.6%-20%), and 5.1% (95% CI: 2.1%-11.6%), respectively. Our findings suggest that radiotherapy plus ICIs may provide acceptable safety and favorable efficacy for SCLC patients.

8. United States pubmed.ncbi.nlm.nih.gov

Safety of thoracic radiotherapy after PD-(L)1 inhibitor treatment in patients with lung cancer. [2022] The safety of thoracic radiotherapy (TRT) after programmed death 1/programmed death ligand 1 (PD-(L)1) inhibitor treatment in patients with lung cancer was scarcely reported. This retrospective study was conducted to evaluate the incidence, severity, and risk factors of symptomatic treatment-related pneumonitis in patients with lung cancer who received this sequential combination.

9. Switzerland pubmed.ncbi.nlm.nih.gov

CAR-T Cells for the Treatment of Lung Cancer. [2022] Adoptive cell therapy with genetically modified T lymphocytes that express chimeric antigen receptors (CAR-T) is one of the most promising advanced therapies for the treatment of cancer, with unprecedented outcomes in hematological malignancies. However, the efficacy of CAR-T cells in solid tumors is still very unsatisfactory, because of the strong immunosuppressive tumor microenvironment that hinders immune responses. The development of next-generation personalized CAR-T cells against solid tumors is a clinical necessity. The identification of therapeutic targets for new CAR-T therapies to increase the efficacy, survival, persistence, and safety in solid tumors remains a critical frontier in cancer immunotherapy. Here, we summarize basic, translational, and clinical results of CAR-T cell immunotherapies in lung cancer, from their molecular engineering and mechanistic studies to preclinical and clinical development.