WCLC 2025 - Posters & ePosters-EP.13.29 Safety and Efficacy of DLL3 CAR-T Cells Armored With dnTGFBR2 in a Patient With Recurrent Small-Cell Lung Cancer

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This report presents the safety and efficacy outcomes of LB2102, an autologous DLL3-targeted CAR-T cell therapy armored with dominant-negative TGFBR2 (dnTGFBR2) designed to overcome tumor-induced immune suppression, in a single patient with recurrent small-cell lung cancer (SCLC). The subject, a 51-year-old female diagnosed with extensive SCLC exhibiting thoracic, liver, and bone metastases, initially responded to standard chemotherapy and immunotherapy but later developed symptomatic brain metastases treated with whole-brain radiation.<br /><br />Enrolled in a phase 1 LB2102 trial, the patient received bridging irinotecan chemotherapy achieving a partial response (PR). However, due to repeated episodes of opioid-induced delirium and concerns about medication compliance leading to removal from the trial, treatment continued under a single-patient investigational new drug protocol. Following lymphodepletion with fludarabine and cyclophosphamide, the patient was infused once with LB2102 at a dose of 2 x 10^6 CAR-T cells/kg.<br /><br />The therapy was well tolerated without dose-limiting toxicities, cytokine release syndrome, or neurotoxicity. Some transient hematologic toxicities (Grade 2 anemia, Grade 4 neutropenia) resolved promptly. Biomarkers such as CRP and ferritin peaked early post-infusion and normalized by six months. Imaging showed stabilization of brain metastases with no new lesions. Importantly, the primary tumor demonstrated significant shrinkage: a 45% reduction by week 12 and 76% reduction at six months post-treatment.<br /><br />Peripheral CAR-T cells expanded (2710/mL, 0.86% of CD3 T cells), circulating tumor cells decreased from 27/mL at baseline to zero, and the patient maintained an ECOG performance status of 1 with ongoing partial response and absence of pain or additional treatment eight months after infusion.<br /><br />In summary, a single infusion of LB2102 demonstrated a favorable safety profile, durable tumor response, and effective CAR-T cell expansion in a patient with recurrent SCLC, supporting further clinical evaluation of DLL3-targeted CAR-T therapy armored with dnTGFBR2 in neuroendocrine lung cancers. The study was funded by Legend Biotech, Novartis, and UK Healthcare.

Asset Subtitle

Zhonglin Hao

Meta Tag

Speaker Zhonglin Hao

Topic Small Cell Lung Cancer and Neuroendocrine Tumors

Keywords

LB2102

DLL3-targeted CAR-T therapy

dominant-negative TGFBR2

small-cell lung cancer

recurrent SCLC

brain metastases

lymphodepletion

cytokine release syndrome

tumor response

clinical trial