NCT07509034

Autologous B7-H3 Chimeric Antigen Receptor T Cells in Previously Treated Extensive-Stage Small Cell Lung Cancer With Recurrent or Refractory Disease

A Phase I Study to Assess the Safety and Antitumor Activity of Autologous B7-H3 Chimeric Antigen Receptor T Cells in Previously Treated Extensive-Stage Small Cell Lung Cancer With Recurrent or Refractory Disease

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

Background: Small cell lung cancer (SCLC) is the deadliest form of lung cancer. Extrapulmonary neuroendocrine cancer (EPNEC) is a similar type of cancer that develops anywhere other than the lungs. EPNEC is also deadly. B7-H3 is a protein often found in SCLC and EPNEC tumor cells. Researchers can modify a person s own T cells, or immune cells, to target B7-H3. When these modified T cells are returned to the body-a treatment called B7-H3 chimeric antigen receptor (CAR) T cell therapy-they may help kill cancer cells. Objective: To test B7-H3 CAR T cell therapy in people with SCLC or EPNEC. Eligibility: People aged 18 years and older with SCLC or EPNEC that either did not respond or returned after treatment. Design: Participants will be screened. They will have blood tests and tests of their heart function. They will have imaging scans. Participants will undergo apheresis: Blood will be taken from the body through a needle. The blood will pass through a machine that separates out the T cells. The remaining blood will be returned to the body through a different needle. The collected T cells will be altered to make them attack cells with B7-H3. Participants will be in the hospital for at least 15 days. They will receive chemotherapy drugs to prepare their body for the treatment. These drugs will be given through a tube attached to a needle inserted into a vein. The modified T cells will be infused through a vein. Participants will remain in the hospital until they are well enough to go home. Follow-up visits will continue for 15 years....

Detailed description

Background: * Small cell lung cancer (SCLC) is the most lethal form of lung cancer with an average life expectancy of 7 to 11 months. * Extrapulmonary neuroendocrine cancers (EP-NEC) are rare and aggressive orphan cancers that share morphological and transcriptomic similarities and potentially therapeutic vulnerabilities with SCLC, with no standard treatments at relapse. * Currently available therapies for patients who have disease progression after first-line chemotherapy-immunotherapy yield limited clinical benefit. Most patients with recurrent/refractory (R/R) SCLC or EP-NEC die within months of disease progression. * Chimeric antigen receptor (CAR) T cells recognize and kill target-expressing tumor cells. * B7 homolog 3 (B7-H3, also known as CD276) is a surface molecule highly expressed in multiple solid tumor types, including SCLC and EP-NEC, with minimal expression in normal human tissues. * B7-H3 targeted CAR T cells have shown preliminary evidence of safety and efficacy in B7-H3 expressing pediatric solid tumors and brain tumors. Objective: * Arm 1: To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of autologous B7-H3 CAR T cells in participants with previously treated recurrent/refractory (R/R) extensive-stage small cell lung cancer (ES-SCLC) or extrapulmonary neuroendocrine cancer (EP-NEC). * Arm 2: To determine Disease Control Rate (DCR). Eligibility: * Age \>=18 years. * Histologically confirmed SCLC or EP-NEC that has recurred following or refractory to first-line therapy. * At least 1 measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2. Design: * This is a Phase I dose escalation/de-escalation study evaluating autologous B7-H3 CAR T cells in participants with R/R SCLC or EP-NEC. * Participants will undergo apheresis for T cell selection. Collected T cells will be transduced with a lentivirus encoding the B7-H3 CAR construct. Participants will receive a lymphodepletion regimen with the intent of enhancing the activity and proliferation of the infused autologous B7-H3 CAR T cells. * During study treatment, participants will have clinical assessments, laboratory evaluations, and imaging studies for safety and response assessment. Blood and tumor samples will be collected for correlative studies at various timepoints. * After study treatment completion, follow-up will be performed for up to 15 years.

Conditions

• Extensive-Stage Small Cell Lung Cancer
• Extrapulmonary Neuroendocrine Carcinoma
• Recurrent or Refractory
• Solid Tumors

Interventions

Type	Name	Description
DRUG	Autologous B7-H3 CAR T	For both dose escalation and expansion phases, B7-H3 CAR T cell infusion will be performed following lymphodepleting therapy. Up to 2 years post the initial infusion, participants will be offered the option for an additional infusion of B7-H3 CAR T cells at the same dose level as the initial dose, with or without LD if eligible.
DRUG	Cyclophosphamide	For both dose escalation and expansion phases, FDA approved lymphodepleting agents, cyclophosphamide and fludarabine will be used on this study prior to the administration of T cells.
DRUG	Fludarabine	For both dose escalation and expansion phases, FDA approved lymphodepleting agents, cyclophosphamide and fludarabine will be used on this study prior to the administration of T cells.

Timeline

• Start date: 2026-04-22
• Primary completion: 2030-01-30
• Completion: 2031-01-30
• First posted: 2026-04-03
• Last updated: 2026-04-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study