Clinical Trial of CD40L-Augmented TIL for EGFR, ALK, ROS1 or HER2-Driven NSCLC
This study is testing a special preparation of your own immune cells, called tumor-infiltrating lymphocytes (TIL), which are stimulated with CD40L. These cells are given along with the drug nivolumab (Opdivo®) to patients with advanced non-small cell lung cancer (NSCLC) that has specific genetic changes (EGFR, ALK, ROS1, or HER2). Before receiving the TIL, you would also receive cyclophosphamide and fludarabine. The main goal is to see how safe this treatment is by tracking any side effects for up to 18 months. You may be eligible if you have Stage IV or recurrent NSCLC with one of these genetic changes, are at least 18 years old, and have had your cancer progress after at least one prior treatment.
- Study design
- This is an interventional study planning to enroll 20 participants. It is not specified if it is randomized or blinded.
- What's involved
- You would have a tumor sample collected for TIL growth. You would receive nivolumab infusions, cyclophosphamide, fludarabine, and a single infusion of TIL cells.
- Compensation
- Not stated in the trial record.
- Follow-up
- Your safety will be monitored for up to 18 months after treatment.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT05681780
Clinical Trial of CD40L-Augmented TIL for Patients With EGFR, ALK, ROS1 or HER2-Driven NSCLC
Recruiting
PHASE1Ages 18+InterventionalTreatmentH. Lee Moffitt Cancer Center and Research InstituteInvestigator-initiated
~20 participants
Updated 2026-03-31 on ClinicalTrials.gov
What's tested:Tumor-infiltrating Lymphocytes (TIL)NivolumabCyclophosphamideFludarabineTumor-infiltrating Lymphocyte TherapyInterleukin-2 (IL2)
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Adverse Events (AE)
Measured over Up to 18 Months
Conditions
Where it's being run
1 sites across 1 statesFlorida1
Study leadership
- Ben Creelan, MD, MS · PRINCIPAL_INVESTIGATOR · Moffitt Cancer Center
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 greater than or equal to 18 years
Diagnosis of stage IV or recurrent non-small cell lung cancer (NSCLC) with an activating genomic alteration within either: EGFR, ALK, ROS1, or ERBB2 receptor tyrosine kinase domains
ECOG performance status of 0 or 1
Expected survival ≥ 4 months
Participants must have had disease progression after at least one prior line of systemic therapy for NSCLC, including appropriate prior targeted therapy for cases in which a targeted therapy is conventionally used for this genomic alteration, prior to initiating nivolumab trial therapy
Measurable disease, not including any lesion that is used for TIL harvest, prior to initiation of nivolumab trial therapy
In accordance with the criteria above, safely accessible tumor for TIL harvest by excisional biopsy expected to yield 1.5 cm3 of tissue, in aggregate
Participants with known brain metastases are eligible for study enrollment if the brain metastases have received appropriate central nervous system-directed therapy or are found to be clinically stable ≤ 10 mm when comparing scans obtained during the screening period with a scan obtained ≥28 days prior, or if the treating physician determines that immediate CNS-specific treatment is not required prior to the first cycle of therapy. Please also refer to eligibility section on corticosteroids below.
Adequate normal organ and marrow function as defined below:
a. Hemoglobin ≥ 9.0 g/dL, with transfusions permissible;
b. Absolute neutrophil count (ANC) ≥ 1000 per mm3);
c. Platelet count ≥ 75,000 per mm3, without platelet transfusions for 7 days;
d. Prothrombin Time ≤ 1.7x the institutional upper limit of normal (ULN), unless participant is receiving intended anticoagulant therapy.
e. Serum bilirubin ≤ 2.0x the institutional ULN, or ≤ 4.0x ULN if confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology) with PI approval.
f. AST/ALT ≤ 2.5x institutional ULN unless liver metastases are present, in which case it must be ≤ 5x ULN
g. Serum creatinine of ≤ 1.5x institutional ULN, or ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN
h. Albumin ≥ 2.0 g/dl
Pulmonary function tests within past 4 months showing DLCO ≥45% of predicted. Adjusted DLCO based on hemoglobin concentration should be used, if available.
Human immunodeficiency virus (HIV)-infected participants must be receiving on effective antiretroviral therapy for past 6 months with undetectable viral load and normal CD4 count
Participants with history of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy, if indicated, and no overt cirrhosis
Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they must have an undetectable HCV viral load and no overt cirrhosis
Participants with a prior or concurrent malignancy must have a natural history which does not have the potential to interfere with safety or efficacy assessment of the investigational regimen
Exclusion
No more than six prior lines of systemic therapy for NSCLC
No prior PD-1 or PD-L1 inhibitor treatment for metastatic NSCLC. Examples of inhibitors include: nivolumab, atezolizumab, pembrolizumab, avelumab, cemplimumab, spartalizumab, or durvalumab.
Participants with rapidly progressing tumors, as judged by the investigator
Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects with vitiligo, Grave's disease, limited site eczema, or limited site plaque psoriasis not requiring systemic treatment (within the past 2 years), or other autoimmune conditions which are not expected to recur, are allowed after approval from the medical monitor or PI
Active leptomeningeal or pachymeningeal metastases, or carcinomatous meningitis. This is due to prognostic implications and timeline for cell therapy
Has a diagnosis of primary immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment.
a. Oral hydrocortisone, only for the purposes of a documented adrenal insufficiency diagnosis, is permitted if ≤ 25 mg daily total dose
b. Inhaled, intranasal, or topical corticosteroids are permitted
Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (other than atrial fibrillation or supraventricular tachycardia), and significant ≥85% carotid artery stenosis
Unresolved toxicity (grade 2) from previous anti-cancer therapy. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripheral neuropathy)
Mean QT interval corrected for heart rate (QTc) ≥480 ms calculated from electrocardiograms (EKGs) using Bazett's Correction
Participants with active systemic infections requiring intravenous antibiotics within 1 week prior to nivolumab. Prophylactic, empiric, or suppressive antibiotics are permitted with sponsor approval
History of allogeneic organ transplant
Participants with psychiatric illness/social situations that would limit compliance with study requirements
Participants with a history of anaphylaxis to beta-lactam antibiotics. Patients may be evaluated for reported history by conducting a history and physical, and a skin test/challenge where appropriate under medical guidance
What this trial measures
- Adverse Events (AE)Up to 18 Months
To characterize the safety profile of CD40L-augmented TIL administered with nivolumab.