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
National Cancer Institute (NCI)
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....
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 mon…
Eligibility
- Age range
- 18–120 years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: * Age \>=18 years old. * Histologically confirmed small cell lung cancer (SCLC) or extrapulmonary neuroendocrine cancers (EP-NEC) that has recurred following or is refractory to first-line therapy. Note: small cell cancers of non-lung primary sites are also eligible. * Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2. * Pulse oximetry \>= 90 percent on room air. * Aspartate Transferase (AST) \< 3 X institutional upper limit of normal (ULN). Note: in case of liver metastases 5 X ULN is acceptable. * Alanine Aminotransferase (ALT) \< 3 X institutional ULN…
Interventions
- DrugAutologous 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.
- DrugCyclophosphamide
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.
- DrugFludarabine
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.
Location
- National Institutes of Health Clinical CenterBethesda, Maryland