Recruiting

Phase 1

CD40L-Augmented TILClinical Trial of CD40L-Augmented TIL for Patients With EGFR, ALK, ROS1 or HER2-Driven NSCLC

Sponsor:

H. Lee Moffitt Cancer Center and Research Institute

Code:

NCT05681780

Conditions

Non Small Cell Lung Cancer

Stage IV Non-small Cell Lung Cancer

Recurrent Non Small Cell Lung Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Tumor-infiltrating Lymphocytes (TIL)

Nivolumab

Cyclophosphamide

Fludarabine

Tumor-infiltrating Lymphocyte Therapy

Study Details

Brief summary:

To determine the effect of a special preparation of cells, called tumor-infiltrating lymphocytes (TIL) stimulated with CD40L, when given with the drug nivolumab, for patients with EGFR, ALK, ROS1, or HER2-genomically altered lung cancer.

Conditions

Non Small Cell Lung Cancer

Stage IV Non-small Cell Lung Cancer

Recurrent Non Small Cell Lung Cancer

Study ID

NCT05681780

Start date

Mar 10, 2023

Status verified date

Mar, 2026

Completion date

Dec, 2027

Anticipated

Primary completion date

Jun, 2026

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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 Criteria:

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

Study Design

Enrollment

20 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: TIL+ Nivolumab

Nivolumab infusion every 3 weeks prior to lymphodepletion chemotherapy with cyclophosphamide/fludarabine, TIL infusion and interleukin-2. Then nivolumab infusion every 4 weeks up to 12 months.

Interventions

Tumor-infiltrating Lymphocytes (TIL)

Tumor harvest for TIL growth in the lab: A sample of the participant's tumor will be collected and sent to the lab for TIL growth. TIL will be prepared and cryopreserved.

Nivolumab

Nivolumab (Opdivo®), 360 mg, IV infusion every 3 weeks prior to TIL infusion, and then after TIL infusion 480 mg ever 4 weeks for up to 12 months.

Cyclophosphamide

Cyclophosphamide will be administered on days -7 and -6.

Fludarabine

Fludarabine will then be infused per institutional standard on Days -7 to -3.

Tumor-infiltrating Lymphocyte Therapy

On day 0, all patients will receive a dose infusion TIL cells.

Interleukin-2 (IL2)

Participants will receive IL-2 for up to 6 doses, based on participants tolerance and investigator judgement. This will be given after the infusion of the T-cells.

Primary outcome measure

Adverse Events (AE) [ Time Frame: Up to 18 Months ]

Central Contacts and Locations

Central contacts

Ben Creelan

813-745-4541 Ben.Creelan@moffitt.org

Locations

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33612

Contacts

Tanner Pearson

813-745-6552 Tanner.Pearson@moffitt.org

Principal Investigator:

Ben Creelan, MD, MS

More Information

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Last update posted

Mar 31, 2026

Last verified

Mar, 2026

Keywords

Lung Cancer
Tumor-Infiltrating Lymphocytes
EGFR Mutation
ALK Rearrangement
ROS1 Rearrangement
ERBB2 Mutation
HER2 Exon 20 Mutation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by H. Lee Moffitt Cancer Center and Research Institute on 2026-03-31.