Phase I Clinical Trial of Autologous Hematopoietic Stem Cell Transplantation-Supported Dose-Intensified Chemotherapy With Adebrelimab as First-Line Treatment for Extensive-Stage Small Cell Lung Cancer.

BACKGROUND

Small cell lung cancer (SCLC) is initially highly sensitive to chemotherapy, which often leads to significant tumor reduction. However, the majority of patients eventually develop resistance, and the disease is further complicated by its "cold" tumor microenvironment, characterized by low tumor immunogenicity and limited CD8+ T cell infiltration. These factors contribute to the poor response to immunotherapy in many cases of extensive-stage SCLC (ES-SCLC). High-dose chemotherapy has shown potential in enhancing tumor cytoreduction, but its use is often limited by severe hematologic toxicity. Combining chemotherapy with immune checkpoint inhibitors (ICIs) can create a synergistic effect by promoting immunogenic cell death and enhancing immune activation. Autologous hematopoietic stem cell transplantation (auto-HSCT) provides a means to support hematopoietic recovery, mitigate chemotherapy-induced myelosuppression, and contribute to immune reconstitution. In this context, the integration of auto-HSCT with dose-intensified chemotherapy and ICIs aims to both protect the bone marrow and enhance antitumor immune responses, potentially overcoming resistance to immunotherapy in ES-SCLC.

METHODS

A phase I, single-center, single-arm trial was designed to evaluate the safety and efficacy of auto-HSCT-supported dose-intensified chemotherapy combined with adebrelimab in treatment-naive ES-SCLC patients. Participants will receive induction chemotherapy followed by stem cell mobilization, apheresis, and cryopreservation. After successful mobilization, consolidation chemotherapy with stem cell reinfusion and granulocyte colony-stimulating factor (G-CSF) support will be performed. Maintenance therapy with adebrelimab continues until disease progression or unacceptable toxicity. Safety and efficacy data, including adverse events, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), will be analyzed.

RESULTS

The study aims to enhance treatment outcomes by overcoming resistance to immuno-chemotherapy and promoting immune reconstitution. The trial is ongoing at the First Affiliated Hospital of Guangzhou Medical University.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT06597513.