Non Small Cell Lung CancerPhase 1NCT05681780
Clinical Trial of CD40L-Augmented TIL for Patients With EGFR, ALK, ROS1 or HER2-Driven NSCLC
A Phase 1 study testing Tumor-infiltrating Lymphocytes (TIL), Nivolumab and Cyclophosphamide in people with Non Small Cell Lung Cancer and Stage IV Non-small Cell Lung Cancer, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer, Recurrent Non Small Cell Lung Cancer
- What is being tested?
- Tumor-infiltrating Lymphocytes (TIL), Nivolumab and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Mar 2023to Dec 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
Tanner Pearson, 813-745-6552, Tanner.Pearson@moffitt.org
Ben Creelan, MD, MS
About this study
Official title: 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.
- Conditions
- Non Small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer, Recurrent Non Small Cell Lung Cancer
- Being tested
- Tumor-infiltrating Lymphocytes (TIL), Nivolumab, Cyclophosphamide, Fludarabine, Tumor-infiltrating Lymphocyte Therapy
- Keywords
- Lung Cancer, Tumor-Infiltrating Lymphocytes, EGFR Mutation, ALK Rearrangement, ROS1 Rearrangement, ERBB2 Mutation, HER2 Exon 20 Mutation
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tumor-infiltrating Lymphocytes (TIL)Biological
Also called 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.
NivolumabDrug
Also called Opdivo
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.
CyclophosphamideDrug
Also called Cytoxan
Cyclophosphamide will be administered on days -7 and -6.
FludarabineDrug
Also called Fludara
Fludarabine will then be infused per institutional standard on Days -7 to -3.
Tumor-infiltrating Lymphocyte TherapyOther
Also called TIL
On day 0, all patients will receive a dose infusion TIL cells.
Interleukin-2 (IL2)Drug
Also called 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.
| Study group | Role | What they receive |
|---|---|---|
| TIL+ Nivolumab | Experimental | 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. Receives: Biological: Tumor-infiltrating Lymphocytes (TIL); Drug: Nivolumab; Drug: Cyclophosphamide; Drug: Fludarabine; Other: Tumor-infiltrating Lymphocyte Therapy; Drug: Interleukin-2 (IL2) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events (AE)
To characterize the safety profile of CD40L-augmented TIL administered with nivolumab.
Measured: Up to 18 Months
Secondary outcomes (3)
Objective Response Rate (ORR)
Proportion of patients with complete response + partial response (CR+PR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Measured: Up to 5 Years
Duration of Response (DOR)
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.
Measured: Up to 5 years
Overall Survival (OS)
The time length of patients living from the date of TIL infusion
Measured: Up to 5 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2023
- Study start10 Mar 2023
- Primary completionJun 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ben Creelan, MD, MS, Principal investigator, Moffitt Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05681780
- Sponsor's protocol ID
- MCC-21971
- Status last verified
- Sep 2026
- First submitted
- 28 Dec 2022
- Last updated
- 16 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Creelan BC, Wang C, Teer JK, Toloza EM, Yao J, Kim S, Landin AM, Mullinax JE, Saller JJ, Saltos AN, Noyes DR, Montoya LB, Curry W, Pilon-Thomas SA, Chiappori AA, Tanvetyanon T, Kaye FJ, Thompson ZJ, Yoder SJ, Fang B, Koomen JM, Sarnaik AA, Chen DT, Conejo-Garcia JR, Haura EB, Antonia SJ. Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial. Nat Med. 2021 Aug;27(8):1410-1418. doi: 10.1038/s41591-021-01462-y. Epub 2021 Aug 12.
PubMed 34385708
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Trial of CD40L-augmented Tumor Infiltrating Lymphocytes (CD40L TIL) for Patients With Oncogene-Driven Advanced Non-Small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT05681780
- Acronym / sponsor ID
- MCC-21971
- Conditions
- Non Small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer, Recurrent Non Small Cell Lung Cancer
- Keywords
- Lung Cancer, Tumor-Infiltrating Lymphocytes, EGFR Mutation, ALK Rearrangement, ROS1 Rearrangement, ERBB2 Mutation, HER2 Exon 20 Mutation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Study start
- 10 Mar 2023 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 12 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TIL+ Nivolumab | Experimental | Biological: Tumor-infiltrating Lymphocytes (TIL), Drug: Nivolumab, Drug: Cyclophosphamide, Drug: Fludarabine, Other: Tumor-infiltrating Lymphocyte Therapy, Drug: Interleukin-2 (IL2)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tumor-infiltrating Lymphocytes (TIL)Also: TILTumor 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. | Biological | TIL+ Nivolumab |
| NivolumabAlso: OpdivoNivolumab (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. | Drug | TIL+ Nivolumab |
| CyclophosphamideAlso: CytoxanCyclophosphamide will be administered on days -7 and -6. | Drug | TIL+ Nivolumab |
| FludarabineAlso: FludaraFludarabine will then be infused per institutional standard on Days -7 to -3. | Drug | TIL+ Nivolumab |
| Tumor-infiltrating Lymphocyte TherapyAlso: TILOn day 0, all patients will receive a dose infusion TIL cells. | Other | TIL+ Nivolumab |
| Interleukin-2 (IL2)Also: IL2Participants 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. | Drug | TIL+ Nivolumab |
Primary outcome
Adverse Events (AE)
Time frame: Up to 18 Months
To characterize the safety profile of CD40L-augmented TIL administered with nivolumab.
3 secondary outcomes
Objective Response Rate (ORR)
Time frame: Up to 5 Years
Duration of Response (DOR)
Time frame: Up to 5 years
Overall Survival (OS)
Time frame: Up to 5 Years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2026.
- Results publication: PubMed 34385708Creelan BC, Wang C, Teer JK, Toloza EM, Yao J, Kim S, Landin AM, Mullinax JE, Saller JJ, Saltos AN, Noyes DR, Montoya LB, Curry W, Pilon-Thomas SA, Chiappori AA, Tanvetyanon T, Kaye FJ, Thompson ZJ, Yoder SJ, Fang B, Koomen JM, Sarnaik AA, Chen DT, Conejo-Garcia JR, Haura EB, Antonia SJ. Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial. Nat Med. 2021 Aug;27(8):1410-1418. doi: 10.1038/s41591-021-01462-y. Epub 2021 Aug 12.
- Moffitt Cancer Center Clinical Trial SearchLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ben Creelan, MD, MS principal investigator
Moffitt Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tumor-infiltrating Lymphocytes (TIL), Nivolumab and Cyclophosphamide in people with Non Small Cell Lung Cancer and Stage IV Non-small Cell Lung Cancer, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ben Creelan (813-745-4541, Ben.Creelan@moffitt.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Events (AE) (time frame: Up to 18 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05681780, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2026; AzTrials last refreshed its copy on 26 Oct 2026.