phase i clinical study of α-pd-l1/dll3 car-t in patients with r/r sclc

Conditions: Small Cell Lung Cancer Extensive Stage

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.

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.

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;

Keywords: extensive stage-sclc dll3 car-t bridge radiotherapy