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

NCT07509034 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10001973001973-C
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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....

Conditions

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

Keywords

B7-H3; CAR-T; Phase I; Immunotherapy

Outcome Measures

Primary Outcomes (2)

• Determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of autologous B7-H3 CAR T cells

  The MTD/MAD is the dose level at which no more than 1 of up to 6 participants experience DLT during autologous B7-H3 CAR T cell treatment, and the dose below that at which at least 2 (of \<=6) participants have DLT as a result of treatment.

  Dose Limiting Toxicity (DLT) period (day 0 through day 28)

• Determine disease control rate (DCR)

  DCR will be reported as a percentage of participants who achieve a complete response, partial response, or stable disease following autologous B7-H3 CAR T cells treatment.

  Until disease progression or 15 years, whichever occurs first

Secondary Outcomes (6)

• Assess safety of autologous B7-H3 CAR T cells infusion

  Study duration

• Objective Response Rate (ORR)

  Until disease progression or 15 years, whichever occurs first

• Duration of Response (DOR)

  Until disease progression or 15 years, whichever occurs first

• Progression Free Survival (PFS)

  Until disease progression or 15 years, whichever occurs first

• Overall Survival (OS)

  Until death or 15 years, whichever occurs first

Study Arms (2)

Dose Escalation

EXPERIMENTAL

Escalating doses of autologous B7-H3 CAR T cells.

Drug: Autologous B7-H3 CAR T; Drug: Cyclophosphamide; Drug: Fludarabine

Dose Expansion

EXPERIMENTAL

Maximum tolerated dose (MTD) or maximum administered dose (MAD) of autologous B7-H3 CAR T cells.

Drug: Autologous B7-H3 CAR T; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

Fludarabine DRUG

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.

Dose Escalation; Dose Expansion

Cyclophosphamide DRUG

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.

Dose Escalation; Dose Expansion

Autologous B7-H3 CAR T DRUG

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.

Dose Escalation; Dose Expansion

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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. Note: in case of liver metastases \<= 5 X ULN is acceptable.
• Total bilirubin \<=2 X institutional ULN.
• Creatinine \<=1.5 X institutional ULN.
• Absolute Neutrophil Count (ANC) \>= 750/mcL.
• Platelet count \>= 75,000/mcL.
• An absolute lymphocyte count (ALC) \>=300/mcL and CD3 plus cell count \>=150/mcL.
• Normal cardiac ejection fraction as defined by \>= 45 percent by echocardiogram (ECHO) at screening.
• At least 1 measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 that has not been previously irradiated.
• Recovered from acute toxic effects of all prior cancer therapy to Grade \<2 per Common Terminology Criteria for Adverse Events (CTCAE) v.6.0 at least one week before apheresis.
• The following criteria must be met prior to apheresis:

You may not qualify if:

• History of anaphylactic reactions attributed to anti-B7-H3 antibodies or compounds of similar chemical or biologic composition to autologous B7-H3 CAR T cells, cyclophosphamide, fludarabine, or other agents used in this study.
• Infection exposure with the human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) as defined below:
• Positive serology for HIV.
• Active HBV infection as demonstrated by test for hepatitis B surface antigen (HBsAg).
• Positive serology for HCV.
• Prior gene therapy using an integrating vector (except for autologous B7-H3 CAR T cells retreatment).
• History of any previous allogeneic hematopoietic stem cell transplant.
• Presence of fungal, bacterial, viral, or other infection is permitted if responding to active treatment.
• Central Nervous System (CNS) disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or autoimmune disease with CNS involvement that may impair the ability to evaluate neurotoxicity.
• Pregnancy confirmed with beta-human chorionic gonadotropin (beta-HCG) serum or urine pregnancy test in IOCBP at screening.
• Uncontrolled intercurrent illness or medical condition(s) evaluated by medical history, physical exam, electrocardiogram (ECG) or situations that would unacceptably increase risk for the participant or impair the ability to evaluate the endpoints of the study.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Recurrence

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Anish Thomas, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Danielle F Pinkiert, R.N.

CONTACT

(240) 858-7566; danielle.pinkiert@nih.gov

Anish Thomas, M.D.

CONTACT

(240) 760-7343; anish.thomas@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2026
• First Posted: April 3, 2026
• Study Start (Estimated): June 17, 2026
• Primary Completion (Estimated): January 30, 2030
• Study Completion (Estimated): January 30, 2031
• Last Updated: June 12, 2026

Record last verified: 2026-05-14

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available as soon as possible or at the time of associated publication. Data not published in a manuscript will be shared via public source once the data set completes QC.
• Access Criteria: Clinical data will be made available upon request and with the permission of the study PI. Genomic data are made available via dbGAP through requests to the data custodians.

Locations

US (1)