Treatment for relapsed small cell lung cancer using CAR-T therapy

Phase I Clinical Study on Safety and Feasibility of DLL3 Targeted α-PD-L1/4-1BB Modifying Chimeric Antigen Receptor T-cells in Patients With Relapsed or Refractory Small Cell Lung Cancer (SCLC)

This study is testing a new CAR-T therapy for people with relapsed small cell lung cancer to see if it can help them after other treatments have failed.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 28 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Sichuan University (Academic / other)
• Drugs / interventions: CAR-T, radiation, Chimeric Antigen Receptor, chemotherapy
• Locations: 1 site (Chengdu, Sichuan)
• Trial ID: NCT06348797 on ClinicalTrials.gov

What this trial studies

This phase I clinical study evaluates the safety and feasibility of α-PD-L1/4-1BB DLL3 CAR-T (BHP01) in patients with relapsed or refractory small cell lung cancer (SCLC) who have progressed after at least one platinum-based chemotherapy regimen. The study employs a 3+3 dose escalation design to determine the appropriate CAR-T cell dose, followed by a dose expansion phase where patients are assigned to groups with or without bridge radiotherapy. The study aims to enroll 12-21 patients initially, with an additional 16 patients in the expansion phase, focusing on the therapeutic potential of targeting DLL3, which is expressed on a majority of SCLC cells.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-70 with recurrent or refractory small cell lung cancer who have progressed after platinum-based chemotherapy.

Not a fit: Patients with small cell lung cancer who have not received prior platinum-based chemotherapy or those with significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with relapsed small cell lung cancer, potentially improving survival outcomes.

How similar studies have performed: While CAR-T therapies have shown promise in other cancers, this specific approach targeting DLL3 in SCLC is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

* Patients with recurrent or refractory small cell lung cancer (SCLC) confirmed by histology or cytology who have relapsed or progressed after treatment with one previous platinum-based regimen;
* Patients can provide sufficient tumor tissue (fresh or paraffin sections, etc.);
* Age 18 \~70 (including boundary), for both men and women;
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
* Life expectancy ≥3 months;
* At least one extracranial measurable lesion (RECIST v1.1) exists；for lesion after radiotherapy， must be confirmed that the lesion has progressed ;
* Patients in limited-stage at the initial diagnosis must undergo radical thoracic radiotherapy and the time of tumor progression is not less than 3 months from the end of radiotherapy, or radical thoracic dose radiotherapy cannot be performed for specific reasons;
* The test results of human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis C and syphilis were negative at screening;
* Female patients or male reproductive age patients and their partners should agree to effective contraception from sighing Informed Consent Form (ICF) to 6 months after the last BHP01 infusion.

Exclusion Criteria:

* Patients with known primary Central Nervous System (CNS) tumor, or meningeal metastasis, or patients with unstable CNS metastasis (symptomatic, requiring hormonal therapy within 4 weeks before investigational treatment, or no radiographic evidence of stabilization of the lesion for more than 4 weeks);
* Received major surgical procedures （except for diagnosis） within 4 weeks before PBMCs collection, or are expected to require major surgical procedures during the study;
* Received Chinese herbal medicine or Chinese patent medicine for anti-tumor indications within 7 days before Peripheral Blood Mononuclear Cells (PBMCs) collection;
* Patients with a history of idiopathic pulmonary fibrosis, mechanical pneumonia (such as bronchiolitis obliterans), drug-induced pneumonia or idiopathic pneumonia, or evidence of active pneumonia by chest computer tomography (CT) at screening \[a history of radiation pneumonia (fibrosis) in the irradiated field may participate in this study\];
* Poorly controlled pleural effusion, pericardial effusion, or ascites requiring repeated drainage procedures (once a month or more frequently);
* Poorly controlled or symptomatic hypercalcemia (ionic calcium\> 1.5 mmol/L, calcium\> 12 mg/dL or corrected calcium\> ULN);
* Presence of active or previous autoimmune diseases or immunodeficiencies, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, etc.;
* Severe infection within 4 weeks before the start of PBMCs collection, including but not limited to hospitalization due to infection, bacteremia, severe pneumonia, or any active infection that may affect the patient's safety;
* Serious cardiovascular and cerebrovascular diseases (such as heart disease ≥New York Heart Association class II, myocardial infarction or cerebrovascular accident), unstable arrhythmia or unstable angina pectoris within 3 months before PBMCs collection;
* Previous treatment with DLL 3 target drugs or CAR-T or other gene-modified T cells;
* Received any other Investigational drug within 28 days prior to PBMCs collection;
* A history of mental illness;
* Incapacitated persons or persons with limited capacity;
* pregnant or lactating females; Males or females who are unwilling to use adequate contraception; Females of childbearing potential are required to undergo a pregnancy study during the screening period;

Where this trial is running

Chengdu, Sichuan

• West China Hospital Sichuan University — Chengdu, Sichuan, China (Recruiting)

Study contacts

• Principal investigator: You Lu, MD — West China Hospital
• Study coordinator: Jianxin Xue, MD

Conditions Small Cell Lung Cancer Extensive Stage; Extensive Stage-SCLC; DLL3 CAR-T; Bridge Radiotherapy