B7-H3 CAR T-cell Therapy for Recurrent Small Cell Lung Cancer and Neuroendocrine Cancers
This study is testing a new treatment called autologous B7-H3 CAR T cells for people with extensive-stage small cell lung cancer (SCLC) or extrapulmonary neuroendocrine cancers (EP-NEC) that have returned or not responded to previous treatments. B7-H3 CAR T cells are your own immune cells (T cells) that have been specially modified to find and kill cancer cells that have a protein called B7-H3. Before receiving the B7-H3 CAR T cells, you will receive other medications called cyclophosphamide and fludarabine. The study aims to find the safest and most effective dose of B7-H3 CAR T cells and see how well it controls the cancer. You must be at least 18 years old and have SCLC or EP-NEC that has recurred or is refractory to first-line therapy to participate.
- Study design
- This is an interventional study with a planned enrollment of 40 participants. It is designed to determine the maximum tolerated dose of the B7-H3 CAR T cells.
- What's involved
- Participants will receive lymphodepleting therapy (cyclophosphamide and fludarabine) before the B7-H3 CAR T cell infusion. You may also be offered an additional infusion of B7-H3 CAR T cells up to two years after the initial infusion.
- Compensation
- Not stated in the trial record.
- Follow-up
- Your disease control rate will be monitored until disease progression or for up to 15 years, whichever comes first.
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NCT07509034
Autologous B7-H3 Chimeric Antigen Receptor T Cells in Previously Treated Extensive-Stage Small Cell Lung Cancer With Recurrent or Refractory Disease
Not Yet Recruiting
PHASE1Ages 18+InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~40 participants
Updated 2026-08-28 on ClinicalTrials.gov
What's tested:Autologous B7-H3 CAR TCyclophosphamideFludarabine
At a glance
Recruiting sites
0 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of autologous B7-H3 CAR T cells
Measured over Dose Limiting Toxicity (DLT) period (day 0 through day 28)
+1 more outcome measured
Conditions
Where it's being run
1 sites across 1 statesMaryland1
Study leadership
- Nicholas P Tschernia, M.D. · PRINCIPAL_INVESTIGATOR · National Cancer Institute (NCI)
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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.
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
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.
What this trial measures
- Determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of autologous B7-H3 CAR T cellsDose Limiting Toxicity (DLT) period (day 0 through day 28)
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.
- Determine disease control rate (DCR)Until disease progression or 15 years, whichever occurs first
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.