Clinical trial Recruiting at 1 site Phase 1 Interventional Ages 18 to 120

Autologous B7-H3 CAR T Cells in Advanced Small Cell Lung Cancer and Extrapulmonary Neuroendocrine Cancer

Official title: 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

Run by National Institutes of Health Clinical Center (CC) · NCT07509034 · Data updated 2026-11-12

This study tests a patient’s own B7-H3 CAR T cells to see if they can help people 18 and older whose small cell lung cancer or EPNEC has come back or hasn’t responded to prior treatment.

More Small Cell Lung Cancer trials

Quick facts

PhasePhase 1
Study typeInterventional
Ages18 Years to 120 Years
SexAll
Enrollment40 (estimated)
SponsorNational Institutes of Health Clinical Center (CC)
NIH
Drugs / interventionsCAR T, Chemotherapy, radiation, methotrexate, cyclophosphamide, fludarabine, prednisone, chimeric antigen receptor, immunotherapy
Locations1 site (Bethesda, Maryland)
StatusRecruiting
StartedOctober 16, 2026
Main results expectedJanuary 30, 2030
Study endsJanuary 30, 2031
Registry record updatedOctober 29, 2026
Trial IDNCT07509034 on ClinicalTrials.gov

Is this trial a fit for you?

Likely a good fit

Adults (≥18 years) with recurrent or refractory extensive-stage SCLC or EPNEC that progressed after or is resistant to first-line therapy and who meet organ-function criteria.

Probably not a fit

Patients with significant comorbidity, abnormal organ function, or tumors not expressing B7-H3 may not benefit from this therapy.

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase 1 trial uses autologous B7-H3 CAR T cells along with lymphodepleting chemotherapy (cyclophosphamide and fludarabine) to target tumors expressing B7-H3. Participants with recurrent or refractory extensive-stage SCLC or EPNEC will be screened and receive treatment if eligible, with monitoring for safety and signals of activity. The study has two arms: determining the maximum tolerated or administered dose and assessing disease control rate. Eligibility requires adequate organ function, ECOG 0-2, and sufficient blood counts, with disease confirmed histologically.

Why it matters

Potential benefit: If successful, patients could experience tumor control or delayed progression from a therapy tailored to their cancer.

How similar studies have gone: Preliminary evidence suggests B7-H3 CAR T cells can be safe and show activity in similar solid tumors, but data in SCLC/EPNEC are limited.

Who can join: the full rules

Show full inclusion / exclusion criteria
* 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% 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 OR creatinine clearance (CrCl) \>= 50 mL/min/1.73m\^2 (calculated by the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula or calculated eGFR provided by a laboratory).
* Absolute Neutrophil Count (ANC) \>= 750/mcL.
* Platelet count \>= 75,000/mcL.
* An absolute lymphocyte count (ALC) \>=300/mcL and CD3+ cell count \>=150/mcL.
* Normal cardiac ejection fraction as defined by \>= 45% 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 excluding the parameters for ANC and ALC mentioned above.
* The following criteria must be met prior to apheresis:

  * Chemotherapy and biologic/targeted agents:

    * \>=14 days since the last dose of standard myelosuppressive chemotherapy.
    * \>= 7 days since the completion of biologic agent, targeted agent, or tyrosine kinase inhibitor therapy.
    * \>= 3 weeks or 5 half-lives (whichever is shorter) since prior therapy with a monoclonal antibody.
  * Radiotherapy:

    * \>= 1 week since the last radiotherapy session.
    * No washout period required for palliative radiation to non-target lesions.
    * \>= 3 weeks since hepatic radiation, chemoembolization, and/or radiofrequency ablation.
  * Steroids and immunosuppressive therapy:

    * Corticosteroids: \>= 2 weeks since the therapeutic doses (\> 0.5 mg/kg/day prednisone or equivalent). Note: Inhaled or topical steroids are not exclusionary.
    * Physiologic replacement doses (up to 5 mg/day prednisone equivalent) are allowed and can be adjusted based on participant's BMI if warranted.
    * \>= 2 weeks since the other immunosuppressive medication (e.g., calcineurin inhibitors, methotrexate, rapamycin, thalidomide, etc.).
  * Anti-PD-1 and any investigational therapies:

    * \>= 2 weeks since Anti-PD-1 monoclonal antibody therapy.
    * \>= 2 weeks or 5 half-lives of the investigational product (whichever is shorter) since any investigational treatment or clinical trial participation.
  * Other criteria:

    * 72 hours since small molecule tyrosine kinase inhibitors (e.g., EGFR inhibitors), PARP inhibitors, or KRAS G12C inhibitors.
* Individuals of childbearing potential (IOCBP) must agree to use highly effective contraception (hormonal, intrauterine device \[IUD\], abstinence, surgical sterilization) at the study entry and up to 12 months after the last dose of combined chemotherapy.

Note: IOCBP is defined as any individual who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal.

* Individuals able to father a child must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) at the study entry and up to 7 months after the last dose of study drugs. We also will recommend individuals able to father a child with partners of childbearing potential ask partners to be on highly effective birth control (hormonal, IUD, surgical sterilization). Individuals able to father a child must not freeze or donate sperm within the same period.
* Nursing participants must be willing to discontinue nursing from study treatment initiation through 6 months after the last dose of the study drug(s).
* Ability of the participant to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

* 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.

Where it's running

  • National Institutes of Health Clinical Center
    Bethesda, Maryland, United States
    Recruiting

Study contacts

  • Principal investigator: Nicholas P Tschernia, M.D. — National Cancer Institute (NCI)
  • Study coordinator: Stephanie N Hicks
  • Email: hickssn2@nih.gov
  • Phone: (240) 760-6159

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How to take part

  1. Review the eligibility criteria above with your treating physician.
  2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
  3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.
Last reviewed 2026-11-14 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.