CAR T-Cell Therapy for Small Cell Lung Cancer

Recruiting at 3 trial locations

Overseen By Adam Schoenfeld, MD

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. ^{1 2 3 4 5}

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. ^{1 2 6 7 8}

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. ^{1 2 3 5 9}

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

Treatment Details

Interventions

• LB2102 (CAR T-cell Therapy)

Trial Overview 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.

Participant Groups

Group I: Experimental LB2102 Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Legend Biotech USA Inc

Lead Sponsor

Trials

3

Recruited

150+

Findings from Research

A novel chimeric antigen receptor (CAR) targeting DLL3 has shown promising antitumor effects in small cell lung cancer (SCLC) models, addressing the urgent need for new therapies due to the poor prognosis of SCLC patients.

The addition of the proinflammatory cytokine IL-18 to CAR T cells significantly enhanced their effectiveness, leading to improved activation of both CAR T cells and other immune cells, suggesting a potential strategy for durable responses in treating DLL3-expressing tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-18-secreting CAR T cells targeting DLL3 are highly effective in small cell lung cancer models. Jaspers, JE., Khan, JF., Godfrey, WD., et al.[2023]

Long-term data from the KEYNOTE-604 trial suggest that using immune checkpoint inhibitors early in the treatment of small cell lung cancer can lead to lasting benefits for patients.

Emerging therapies, such as bispecific T-cell engagers and various combination treatments, show promise as effective options for patients in later stages of treatment for small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SCLC's Treatment Arsenal Improving. [2022]

Current treatment for limited small cell lung cancer primarily involves cisplatin and etoposide chemotherapy, which has not yet been replaced by newer drugs, indicating its continued efficacy in this setting.

Concurrent chemoradiotherapy offers a 25% chance of cure, but optimal treatment parameters are still being studied in ongoing phase III trials, highlighting the need for collaboration between oncologists to enhance treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of limited small cell lung cancer: an old or new challenge? Blackhall, F., Faivre-Finn, C.[2011]

In a pilot study of 58 small cell lung cancer (SCLC) patients, those receiving cellular immunotherapy (CIT) as maintenance therapy had a significantly longer overall survival (20 months) compared to the control group (11.5 months), indicating that CIT may enhance survival outcomes after initial chemotherapy.

CIT showed minimal adverse effects, suggesting it is a safe option for patients, and it may be a promising strategy to improve treatment for SCLC, although further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cellular immunotherapy as maintenance therapy prolongs the survival of the patients with small cell lung cancer. Ding, X., Cao, H., Chen, X., et al.[2018]

The bispecific T-cell engager BI 764532 targets DLL3, a protein found on poorly differentiated neuroendocrine carcinomas like small-cell lung cancer (SCLC), and has shown promising results in inducing complete tumor regression in preclinical models.

This ongoing phase I clinical trial aims to establish the maximum tolerated dose of BI 764532 while assessing its safety, tolerability, pharmacokinetics, and preliminary efficacy in patients with SCLC or other DLL3-positive neuroendocrine carcinomas.

NCBI (Pubmed)

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. Wermke, M., Felip, E., Gambardella, V., et al.[2022]

Combining immunotherapy with radiotherapy in patients with small-cell lung cancer (SCLC) shows promising efficacy, with median progression-free survival ranging from 4.5 to 12.5 months and overall survival from 8.4 months to not reached.

The safety profile of this combination treatment is acceptable, with incidences of severe adverse events such as grade 3 or higher pneumonitis (8.7%) and lung infections (6.7%) being relatively low.

NCBI (Pubmed)

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. Wang, Q., Liu, AH., Fan, HJ., et al.[2022]

In a study of 96 lung cancer patients who received thoracic radiotherapy (TRT) after PD-(L)1 inhibitor treatment, nearly 49% developed symptomatic treatment-related pneumonitis, indicating a significant safety concern with this treatment sequence.

Independent risk factors for developing pneumonitis included pulmonary emphysema and lung V20 exposure, highlighting the need for careful patient selection and monitoring when using TRT after PD-(L)1 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of thoracic radiotherapy after PD-(L)1 inhibitor treatment in patients with lung cancer. Chen, Y., Liu, X., Huang, Z., 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]

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]

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]

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

SCLC's Treatment Arsenal Improving. [2022]

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

Treatment of limited small cell lung cancer: an old or new challenge? [2011]

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

Cellular immunotherapy as maintenance therapy prolongs the survival of the patients with small cell lung cancer. [2018]

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]

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]

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

Safety of thoracic radiotherapy after PD-(L)1 inhibitor treatment in patients with lung cancer. [2022]

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

CAR-T Cells for the Treatment of Lung Cancer. [2022]