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

March 26, 2026 updated by: H. Lee Moffitt Cancer Center and Research Institute

Clinical Trial of CD40L-augmented Tumor Infiltrating Lymphocytes (CD40L TIL) for Patients With Oncogene-Driven Advanced Non-Small Cell Lung Cancer (NSCLC)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt Cancer Center
        • Principal Investigator:
          • Ben Creelan, MD, MS
        • Contact:
        • Principal Investigator:
          • Daniel Abate Daga, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Biological: 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.
Other Names:
  • TIL
Drug: 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.
Other Names:
  • Opdivo
Drug: Cyclophosphamide
Cyclophosphamide will be administered on days -7 and -6.
Other Names:
  • Cytoxan
Drug: Fludarabine
Fludarabine will then be infused per institutional standard on Days -7 to -3.
Other Names:
  • Fludara
Other: Tumor-infiltrating Lymphocyte Therapy
On day 0, all patients will receive a dose infusion TIL cells.
Other Names:
  • TIL
Drug: 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.
Other Names:
  • IL2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Events (AE)
Time Frame: Up to 18 Months
To characterize the safety profile of CD40L-augmented TIL administered with nivolumab.
Up to 18 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: Up to 5 Years
Proportion of patients with complete response + partial response (CR+PR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Up to 5 Years
Duration of Response (DOR)
Time Frame: Up to 5 years
The time from the date of the first documentation of initial response (CR or PR) to the date of the first documentation of progressive disease (PD) or death due to any cause.
Up to 5 years
Overall Survival (OS)
Time Frame: Up to 5 Years
The time length of patients living from the date of TIL infusion
Up to 5 Years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Investigators

  • Principal Investigator: Ben Creelan, MD, MS, Moffitt Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 10, 2023

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

December 28, 2022

First Submitted That Met QC Criteria

December 28, 2022

First Posted (Actual)

January 12, 2023

Study Record Updates

Last Update Posted (Actual)

March 31, 2026

Last Update Submitted That Met QC Criteria

March 26, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCC-21971

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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