Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
Prospective, interventional multicenter study evaluating adoptive cell therapy (ACT) via
infusion of LN-144 (autologous TIL) followed by interleukin 2 (IL-2) after a nonmyeloablative
lymphodepletion (NMA LD) preconditioning regimen.
Phase
Phase 2
Funding Agency/Sponsor
Industrial
Disease
Cutaneous Malignancies
Enrollment Eligibility
Patients must meet all of the following inclusion criteria to be eligible for participation
in the study:
Criteria for Inclusion:
1. Patients with unresectable or metastatic melanoma (Stage IIIc or Stage IV)
2. Patients must have progressed following ≥ one prior systemic therapy including a
programmed cell death protein-1 (PD-1) blocking antibody; and if proto-oncogene B-Raf
(BRAF) V600 mutation-positive, a BRAF inhibitor or BRAF inhibitor in combination with
mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor
3. At least one measurable target lesion, as defined by RECIST v1.1
- Lesions in previously irradiated areas (or other local therapy) should not be
selected as target lesions, unless treatment was ≥ 3 months prior to Screening,
and there has been demonstrated disease progression in that particular lesion
4. At least one resectable lesion (or aggregate of lesions resected) of a minimum 1.5 cm
in diameter post-resection to generate TIL; surgical removal with minimal morbidity
(defined as any procedure for which expected hospitalization is ≤ 3 days)
5. Patients must be ≥ 18 years of age at the time of consent. Enrollment of patients > 70
years of age may be allowed after consultation with the Medical Monitor
6. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0 or 1 and an estimated life expectancy of ≥ 3 months
7. In the opinion of the Investigator, patients must be able to complete all
study-required procedures
8. Patients must have the following hematologic parameters:
- Absolute neutrophil count (ANC) ≥ 1000/mm3
- Hemoglobin (Hb) ≥ 9.0 g/dL
- Platelet ≥ 100,000/mm3
9. Patients must have adequate organ function:
- Serum alanine transaminase (ALT)/serum glutamic-pyruvic transaminase (SGPT) and
aspartate transaminase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) ≤ 3
times the upper limit of normal (ULN); patients with liver metastasis ≤ 5 times
ULN
- Estimated creatinine clearance (eCrCl) ≥ 40 mL/min using the Cockcroft-Gault
formula
- Total bilirubin ≤ 2 mg/dL
- Patients with Gilbert's syndrome must have a total bilirubin ≤ 3 mg/dL
10. Patients must have recovered from all prior therapy-related adverse events (AEs) to ≤
Grade 1 (per Common Terminology Criteria for Adverse Events [CTCAE] v4.03), except for
alopecia or vitiligo, prior to Enrollment (tumor resection)
- Patients with documented ≥ Grade 2 diarrhea or colitis as a result of previous
treatment with immune checkpoint inhibitor(s) must have been asymptomatic for at
least 6 months and/or had a normal colonoscopy post-immune checkpoint inhibitor
treatment, by visual assessment, prior to tumor resection
11. Patients must have a washout period ≥ 28 days from prior anticancer therapy(ies) to
the start of the planned NMA-LD preconditioning regimen:
- Targeted therapy: MEK/BRAF or other targeted agent
- Chemotherapy
- Immunotherapy: anti-cytotoxic T lymphocyte-associated antigen 4
(CTLA-4)/anti-PD-1, other monoclonal antibody (mAb), or vaccine
- Palliative radiation therapy is permitted so long as it does not involve lesions
being selected for TIL, or as target or non-target lesions. Washout is not
required if all related toxicities have resolved to ≤ Grade 1 as per CTCAE v4.03
12. Patients of childbearing potential or their partners of childbearing potential must be
willing to take the appropriate precaution to avoid pregnancy or fathering a child for
the duration of the study and practice an approved, highly effective method of birth
control during treatment and for 12 months after receiving the last protocol-related
therapy
- Approved methods of birth control are as follows:
- Combined (estrogen and progesterone containing) hormonal birth control associated
with inhibition of ovulation: oral, intravaginal, transdermal
- Progesterone-only hormonal birth control associated with inhibition of ovulation:
oral, injectable, implantable
- Intrauterine device (IUD)
- Intrauterine hormone-releasing system (IUS)
- Bilateral tubal occlusion
- Vasectomized partner
- True sexual abstinence when this is in line with the preferred and usual
lifestyle of the patient. Periodic abstinence (eg, calendar ovulation,
symptothermal, post-ovulation methods) is not acceptable
13. 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 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 OS Follow-up Period
14. Patients have provided written authorization for use and disclosure of protected
health information
Criteria for Exclusion:
Patients who meet any of the following criteria are not eligible for participation in this
study:
1. Patients who have been shown to be BRAF mutation positive (V600), but have not
received prior systemic therapy with a BRAF inhibitor alone or a BRAF inhibitor in
combination with a MEK inhibitor
2. Patients who have received an organ allograft or prior cell transfer therapy
3. Patients with melanoma of uveal/ocular origin
4. Patients who have a history of hypersensitivity to any component or excipient of
LN-144 or other study drugs:
- NMA-LD preconditioning regimen (cyclophosphamide, mesna, and fludarabine)
- Antibiotics (ABX) of the aminoglycoside group (ie, 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
5. Patients with symptomatic and/or untreated brain metastases (of any size and any
number)
- Patients with definitively treated brain metastases may be considered for
Enrollment, and must be stable for ≥ 14 days prior to beginning the NMA LD
preconditioning regimen
6. Patients who are on chronic systemic steroid therapy for any reason
7. Patients who have active medical illness(es) that would pose increased risk for study
participation, including: active systemic infections requiring systemic ABX,
coagulation disorders, or other active major medical illnesses of the cardiovascular,
respiratory, or immune system
8. Patients who have any form of primary immunodeficiency (such as severe combined
immunodeficiency disease [SCID] and acquired immunodeficiency syndrome [AIDS])
9. Patients who have a left ventricular ejection fraction (LVEF) < 45% or New York Heart
Association (NYHA) functional classification > Class 1
- Patients ≥ 60 years of age and who have a history of ischemic heart disease,
chest pain, or clinically significant atrial and/or ventricular arrhythmias must
have a cardiac stress test. Patients with any irreversible wall movement
abnormalities are excluded
10. Patients who have a documented forced expiratory volume in 1 second (FEV1) of ≤ 60%
11. Patients who have had another primary malignancy within the previous 3 years (with the
exception of carcinoma in situ of the breast, cervix, or bladder; localized prostate
cancer; and non-melanoma skin cancer that has been adequately treated)
12. Patients who have received a live or attenuated vaccine within 28 days of beginning
the NMA-LD preconditioning regimen
13. Patients who are pregnant or breastfeeding
14. Patients whose cancer requires immediate attention or who would otherwise suffer a
disadvantage by participating in this trial
15. Patients protected by the following constraints:
- Hospitalized persons without consent or persons deprived of liberty because of a
judiciary or administrative decision
- Adult persons with a legal protection measure or persons who cannot express their
consent
- Patients in emergency situations who cannot consent to participate in the trial