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)
| Registry | NCT06348797 |
|---|---|
| Status | Recruiting |
| Phase | Phase 1 |
| Study type | Interventional; na, single group, masking: none, treatment |
| Enrollment | 30 (Estimated) |
| Sponsor | Sichuan University (Other); collaborators: Chengdu Brilliant Pharmaceutical Co., Ltd. |
| Conditions | Small Cell Lung Cancer Extensive Stage |
| Interventions | α-PD-L1/4-1BB DLL3 CAR-T (BHP01) (Drug) |
| Dates | start 2025-04-03, primary completion 2026-12-30 (estimated), completion 2026-12-31 (estimated), first posted 2024-04-05, last updated 2026-07-21 |
| Locations | 1 site in China |
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All trials for Small Cell Lung Cancer Extensive Stage All trials of α-PD-L1/4-1BB DLL3 CAR-T (BHP01)
A study to evaluate the safety and feasibility of α-PD-L1/4-1BB DLL3 Chimeric Antigen Receptor (CAR)-T (BHP01) in patients with Relapsed/Refractory Small Cell Lung Cancer (SCLC) and determine the appropriate CAR-T cell dose. Next, In dose expansion phase, patients were assign two groups with/without bridge radiotherapy.
Small cell lung cancer (SCLC) accounts for about 15% of lung cancers, and two-thirds of cases are metastatic at the time of diagnosis. The inhibitory notch ligand delta-like ligand 3 (DLL3) is aberrantly expressed on the surface of up to 85% of SCLC cells and minimally expressed in normal tissues, making it a compelling therapeutic target. This is a phase I, first-in-human, 3+3 dose escalation study to evaluate the safety and feasibility of BHP01 in patents with relapsed/refractory SCLC who progressed after at least 1 platinum based chemotherapy regimen.This is a dose escalation and dose expansion study. 12-21 patients with relapsed/refractory SCLC are planned to be enrolled (Group Pre-A/A/B/C). After the Dose-limiting toxicity (DLT) observation period of the related dose group finished.16 patients are planned to enroll in dose expansion phase who was assign two groups with/without bridge radiotherapy.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| α-PD-L1/4-1BB DLL3 CAR-T (BHP01) Treatment | Experimental | Drug: α-PD-L1/4-1BB DLL3 CAR-T (BHP01) | The Patients enrolled will be sequentially assigned to the corresponding dose level, BHP01 was administered intravenous infusion at different cell dose levels. The patients were received multiple-dose infusion according to investigator's evaluation. |
Sex: All, ages: 18 Years to 70 Years
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 1 months from the end of radiotherapy, or radical thoracic dose radiotherapy cannot be performed for specific reasons; The time elapsed since the completion of radiotherapy for brain metastases shall be no less than 1 months； * The test results of human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis C and syphilis were negative at screening (If hepatitis B core antibody (HBcAb) is positive, additional HBV DNA testing is required, and subjects whose test result is less than the reference value can be included in the study) ; * 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;
| Facility | City | Country | Status |
|---|---|---|---|
| West China Hospital Sichuan University | Chengdu, Sichuan | China | Recruiting |