CAR T-Cell Therapy for Small Cell Lung Cancer

Recruiting at 3 trial locations

Overseen By Adam Schoenfeld, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Legend Biotech USA Inc

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

Disqualifiers: Immunodeficiency, Brain metastasis, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days

41 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called LB2102, a type of CAR T-cell therapy, for individuals with certain types of lung cancer, specifically extensive stage small cell lung cancer and large cell neuroendocrine lung cancer. The goal is to assess the safety of this treatment and its effects on the cancer. The trial seeks participants who have tried other treatments without success and are open to trying something new. Participants must have a lung cancer diagnosis that cannot be surgically removed and have undergone at least one previous treatment. 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 new therapy.

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.

Is there any evidence suggesting that LB2102 is likely to be safe for humans?

Research has shown that the treatment LB2102, a type of CAR T-cell therapy, appears safe. In one study, patients with small cell lung cancer generally tolerated LB2102 well, with most experiencing no severe side effects. Some patients also showed early signs of the treatment working against the cancer, which is encouraging.

However, as this research is in its early stages, scientists are still determining the best dose and monitoring for adverse reactions. Although the FDA has not yet approved the treatment for this type of cancer, testing it in humans suggests some confidence in its safety. Always discuss potential risks and benefits with a doctor before deciding to join a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for small cell lung cancer, which typically involve chemotherapy and radiation, LB2102 is unique because it uses a cutting-edge approach called CAR T-cell therapy. This therapy involves engineering a patient's own immune cells to specifically target and destroy cancer cells, focusing on the DLL3 protein found on these cancer cells. Researchers are excited about LB2102 because it offers a more targeted attack on cancer, potentially leading to fewer side effects and improved effectiveness compared to traditional treatments. This precision in targeting cancer cells could mean a significant advancement in how small cell lung cancer is treated.

What evidence suggests that LB2102 might be an effective treatment for small cell lung cancer?

Research has shown that LB2102, a type of CAR T-cell therapy under study in this trial, could be promising for treating small cell lung cancer and large cell neuroendocrine cancer. Studies have found that it is generally safe and shows early signs of stopping tumor growth in patients who have tried other treatments. LB2102 targets a protein called DLL3, often found on these cancer cells, helping the immune system recognize and attack the cancer. Initial findings suggest that patients handle the treatment well, with manageable side effects. While more research is needed, these early results are encouraging for those considering this therapy. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• LB2102

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

AMG 119, a CAR-T cell therapy targeting DLL3, shows promising results in patients with relapsed/refractory small cell lung cancer, demonstrating robust cellular expansion and long-lasting persistence.

The therapy has been found to be clinically safe and well tolerated, with no reported dose-limiting toxicities, marking a significant step towards CAR-T cell therapies for solid tumors.

NCBI (Pubmed)

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). Zhou, D., Byers, LA., Sable, B., et al.[2023]

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]

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]

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]

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]

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]

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.8104

Safety, tolerability, and preliminary efficacy results of a ... This ongoing, open-label, multicenter, phase 1 study evaluates LB2102 in patients with SCLC/LCNEC who are relapsed/refractory to ≥1 prior line of therapy.

2. asco.org asco.org/abstracts-presentations/ABSTRACT506978

Safety, tolerability, and preliminary efficacy results of a ... This ongoing, open-label, multicenter, phase 1 study evaluates LB2102 in patients with SCLC/LCNEC who are relapsed/refractory to ≥1 prior line of therapy.

3. onclive.com onclive.com/view/lb2102-car-t-cell-therapy-is-well-tolerated-yields-disease-control-in-r-r-sclc-and-lcnec

LB2102 CAR T-Cell Therapy Is Well Tolerated, Yields ... The DLL3-directed CAR T-cell therapy LB2102 was safe with preliminary antitumor activity in small cell lung cancer and large cell neuroendocrine carcinoma.

4. investors.legendbiotech.com investors.legendbiotech.com/news-releases/news-release-details/legend-biotech-announces-fda-clearance-ind-application-lb2102

Press Release Details Legend Biotech Announces FDA Clearance of IND Application for LB2102 in Extensive Stage Small Cell Lung Cancer · Legend Biotech Corporation (NASDAQ: LEGN) ( ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1556086425026759

EP.13.29 Safety and Efficacy of DLL3 CAR-T Cells ... LB2102 comprises autologous DLL3-targeted CAR-T cells armored with dominant-negative TGBFR2 to overcome tumor-mediated immunosuppression.