Phase I Clinical Study of α-PD-L1/DLL3 CAR-T in Patients With R/R SCLC

NCT ID: NCT06348797

Last Updated: 2025-05-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-03
• Study Completion Date: 2026-12-31

Brief Summary

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.

Detailed Description

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.

Conditions

Small Cell Lung Cancer Extensive Stage

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

α-PD-L1/4-1BB DLL3 CAR-T (BHP01) Treatment

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.

Group Type: EXPERIMENTAL

α-PD-L1/4-1BB DLL3 CAR-T (BHP01)

Intervention Type: DRUG

Preconditioning with fludarabine, cyclophosphamide, based chemotherapy regimen at sub-clinical doses; Bridge radiotherapy with 15 Gray (Gy)/5 fractions; α-PD-L1/4-1BB DLL3 CAR-T (BHP01): the first dose was 5x10\^5/kg.

Interventions

α-PD-L1/4-1BB DLL3 CAR-T (BHP01)

Preconditioning with fludarabine, cyclophosphamide, based chemotherapy regimen at sub-clinical doses; Bridge radiotherapy with 15 Gray (Gy)/5 fractions; α-PD-L1/4-1BB DLL3 CAR-T (BHP01): the first dose was 5x10\^5/kg.

Intervention Type: DRUG

Other Intervention Names

Bridge radiotherapy

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;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chengdu Brilliant Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Sichuan University

OTHER

Sponsor Role: lead

Responsible Party

You Lu

Chair of Department of Thoracic Cancer

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

You Lu, MD

Role: PRINCIPAL_INVESTIGATOR

West China Hospital

Locations

West China Hospital Sichuan University

Chengdu, Sichuan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jianxin Xue, MD

Role: CONTACT

killercell@163.com

18982251798

Zhuoran Yao, MD

Role: CONTACT

yaozhuoran@outlook.com

13261660839

Facility Contacts

Li Li

Role: primary

tracy.li_2010@hotmail.com

+086-02885424619

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Other Identifiers

BHP01-01

Identifier Type: -

Identifier Source: org_study_id