| Eligibility |
Inclusion Criteria:
- Patient must be 18 to 75 years of age
- Must have a confirmed diagnosis of Stage IIIB-D locally advanced or Stage IV melanoma
(American Joint Committee on Cancer [AJCC] 8th edition) with measurable disease in the
lymph node(s) documented by computed tomography (CT) or ultrasound imaging (>= 15 mm
short axis) or by physical exam. Patients must also have measurable primary site of
disease, including cutaneous and/or intransit metastases by imRECIST (>= 20 mm chest
x-ray [CXR], >= 10 mm CT, or >= 10 mm by exam)
- No prior therapy is allowed
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0 or 1 and an estimated life expectancy of >= 3 months in the opinion of the
investigator
- Patients must have at least one easily accessible measurable tumor-involved lymph
node(s) documented by CT or ultrasound imaging for TIL harvest
- Patients must be amenable to have ultrasound examination of measurable lymph node(s)
and have pathologic confirmation of melanoma metastases in the lymph node (fine needle
aspiration [FNA] acceptable) in the 28 days preceding the first administration of the
treatment
- Patients with and without BRAF V600E/K mutations are included.
- Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial.
- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better.
- Patients with a history of herpes simplex virus (HSV) infection must have been
treated. Patients with a history of Epstein-Barr virus (EBV) or cytomegalovirus (CMV)
infection must be asymptomatic and have low viral loads
- Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial
- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional classification. To be
eligible for this trial, patients should be class 2B or better
- Women must not be pregnant or breast-feeding due to potential harm to an unborn fetus
and possible risk of adverse events in nursing infants with the anti-PD-1 regimen(s)
being used.
- All females of childbearing potential must have a blood test or urine study
within 14 days prior to registration to rule out pregnancy.
- A female of childbearing potential is defined as any woman, regardless of sexual
orientation, or whether they have undergone tubal ligation, who meets the
following criteria: 1) has achieved menarche at some point, 2) has not undergone
a hysterectomy or bilateral oophorectomy, or 3) has not been naturally
postmenopausal for at least 24 consecutive months (i.e., has had menses at any
time in the preceding consecutive months)
- Women of childbearing potential and sexually active males must not conceive or father
children by using accepted and effective method(s) of contraception or by abstaining
from sexual intercourse from the time of study registration and continuing until at
least 5 months after the last dose of anti-PD-1 treatment for female patients and for
at least 7 months after the last dose of anti-PD-1 treatment for male patients who are
sexually active with a woman of childbearing potential (WOCBP).
- Patients must have adequate organ and marrow function as defined below at study
enrollment and prior to surgical resection. (these labs must be obtained = 4 weeks
prior to protocol registration and =1 week prior to surgery):
- Hemoglobin >= 10 g/dL
- Neutrophils >= 1500/ul
- Leukocytes >= 3000/ul
- Lymphocytes >= 700/ul
- Blood platelet >= 100,000/ul
- Serum creatinine =< 1.5 x upper limit of normal or creatinine clearance (CrCl) >= 40
mL/min (if using the Cockcroft-Gault formula)
- Serum bilirubin =< 2.0 mg/dL
- Total bilirubin =< 1.5 x upper limit of normal (except for patients with Gilbert
syndrome, who can have total bilirubin < 3 mg/dL)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2 x upper limit
of normal
- Lactate dehydrogenase (LDH) =< 1.5 x upper limit of normal
- Patients (or legally authorized representative) must have the ability to understand
the requirements of the study, have provided written informed consent as evidenced by
signature on an informed consent form (ICF) approved by an Institutional Review
Board/Independent Ethics Committee (IRB/IEC), and agree to abide by the study
restrictions and return to the site for the required assessments, including the RFS
Follow-up Period
Exclusion Criteria:
- Ocular/uveal melanoma
- Chemotherapy or radiotherapy within 4 weeks before baseline (6 weeks for nitroso-urea
and mitomycin C)
- Contraindication for the use of vasopressor agents
- Patients with HIV active infection or seropositivity are excluded. Patients with
active Hep B or Hep C based on serology and viral load are excluded. Patients with
active CMV or EBV based on serology and viral load are excluded.
- History or current manifestation of severe progressive heart disease (congestive heart
failure with LVEF < 50% by echocardiogram or MUGA scan, coronary artery disease,
uncontrolled arterial hypertension, uncontrolled arrhythmia, or myocardial infarction
in the past 6 months.
- Patients with active interstitial lung disease (ILD)/pneumonitis or a history of
ILD/pneumonitis requiring treatment with systemic steroids.
- Patients should be excluded if they had prior treatment with an anti- PD-1,
anti-PD-L1, anti-PD-L2, anti-CTLA4 antibody, or any other antibody or drug
specifically targeting T-cell costimulation or immune checkpoint pathways.
- Patients who have a history of hypersensitivity to immune checkpoint therapy drug(s)
or any component or excipient of LN-144 or other study drugs:
- Nivolumab, pembrolizumab, or related products
- Any monoclonal antibody
- NMA-LD preconditioning regimen (cyclophosphamide, mesna, and fludarabine)
- Proleukin, aldesleukin, IL-2
- Antibiotics (ABX) of the aminoglycoside group (i.e., streptomycin, gentamicin);
except those who are skin-test negative for gentamicin hypersensitivity
- Any component of the LN-144 infusion product formulation including dimethyl
sulfoxide (DMSO), human serum albumin (HSA), IL-2, and dextran-40
- History of chronic autoimmune disease (Addison's disease, multiple sclerosis, Graves'
disease, rheumatoid arthritis, systemic lupus erythematosus, etc…) except patient with
active vitiligo or a history of vitiligo. Patients with history of psoriasis is
allowed
- History of inflammatory bowel disease, celiac disease, or other chronic
gastrointestinal conditions associated with diarrhea.
- Patients who have had another primary malignancy within the previous 3 years (except
for those which do not require treatment or have been curatively treated >1 year ago,
and in the judgment of the Investigator, does not pose a significant risk of
recurrence including, but not limited to, non-melanoma skin cancer, DCIS, LCIS,
prostate cancer Gleason score =6).
- Any serious, acute or chronic illness (i.e., active infection) needing antibiotics
administration, coagulation's disorders, or any medical disorder requiring
unauthorized concomitant treatment described in this study.
- Positive serology for HTLV1/HTLV2, or syphilis.
- Patients should be excluded if they have a condition requiring systemic treatment with
either corticosteroids (> 10 mg daily prednisone equivalents) or other
immunosuppressive medications within 14 days before study drug administration. Inhaled
or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents
are permitted in the absence of active autoimmune disease. Patients are permitted to
use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids
(with minimal systemic absorption). Physiologic replacement doses of systemic
corticosteroids are permitted, even if > 10 mg/day prednisone equivalents. A brief
course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment
of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by
contact allergen) is permitted.
- Patients who have obstructive or restrictive pulmonary disease and have a documented
forced expiratory volume in 1 second (FEV1) of = 60% of predicted normal:
- If a patient is not able to perform reliable spirometry due to abnormal upper
airway anatomy (i.e., tracheostomy), a 6- minute walk test may be used to assess
pulmonary function.
- Patients who are unable to walk a distance of at least 80% predicted for age and
sex or demonstrates evidence of hypoxia at any point during the test (SpO2 < 90%)
are excluded.
- Active infections, including COVID-19, within 30 days, unless deemed fully
resolved/treated by the study PI.
- Participated in another clinical study with an investigational product within 21 days
of the initiation of treatment.
- Adults under a legal protection regime (i.e., guardianship, trusteeship).
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