Trial Title:
Clinical Trial of CD40L-Augmented TIL for Patients With EGFR, ALK, ROS1 or HER2-Driven NSCLC
NCT ID:
NCT05681780
Condition:
Non Small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Recurrent Non Small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Cyclophosphamide
Nivolumab
Fludarabine
Interleukin-2
Conditions: Keywords:
Lung Cancer
Tumor-Infiltrating Lymphocytes
EGFR Mutation
ALK Rearrangement
ROS1 Rearrangement
ERBB2 Mutation
HER2 Exon 20 Mutation
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Tumor-infiltrating Lymphocytes (TIL)
Description:
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.
Arm group label:
TIL+ Nivolumab
Other name:
TIL
Intervention type:
Drug
Intervention name:
Nivolumab
Description:
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.
Arm group label:
TIL+ Nivolumab
Other name:
Opdivo
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Cyclophosphamide will be administered on days -7 and -6.
Arm group label:
TIL+ Nivolumab
Other name:
Cytoxan
Intervention type:
Drug
Intervention name:
Fludarabine
Description:
Fludarabine will then be infused per institutional standard on Days -7 to -3.
Arm group label:
TIL+ Nivolumab
Other name:
Fludara
Intervention type:
Other
Intervention name:
Tumor-infiltrating Lymphocyte Therapy
Description:
On day 0, all patients will receive a dose infusion TIL cells.
Arm group label:
TIL+ Nivolumab
Other name:
TIL
Intervention type:
Drug
Intervention name:
Interleukin-2 (IL2)
Description:
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.
Arm group label:
TIL+ Nivolumab
Other name:
IL2
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.
Criteria for eligibility:
Criteria:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Moffitt Cancer Center
Address:
City:
Tampa
Zip:
33612
Country:
United States
Status:
Recruiting
Contact:
Last name:
Tanner Pearson
Phone:
813-745-6552
Email:
Tanner.Pearson@moffitt.org
Investigator:
Last name:
Ben Creelan, MD, MS
Email:
Principal Investigator
Investigator:
Last name:
Daniel Abate Daga, PhD
Email:
Principal Investigator
Start date:
January 23, 2023
Completion date:
February 2027
Lead sponsor:
Agency:
H. Lee Moffitt Cancer Center and Research Institute
Agency class:
Other
Source:
H. Lee Moffitt Cancer Center and Research Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05681780
https://moffitt.org/clinicaltrialssearch?DiseaseSite=&q=21971
