A study to find out if an investigational product, called LN-144 (also called tumour infiltrating lymphocytes) is safe and beneficial in the treatment of patients with metastatic melanoma
- Conditions
- Metastatic melanomaMedDRA version: 21.1Level: PTClassification code 10027480Term: Metastatic malignant melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-000760-15-IT
- Lead Sponsor
- IOVANCE BIOTECHNOLOGIES, INC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 85
a. Patients with unresectable or metastatic melanoma (Stage IIIc or
Stage IV) who progressed following = 1 lines of prior systemic
therapy, including immune checkpoint inhibitor (eg, anti-PD-1), and
if BRAF mutation-positive, after BRAF inhibitor systemic therapy.
Patients must have no other therapy options that are expected to have
significant benefit in the opinion of the Investigator and must have:
• At least 1 measurable target lesion, as defined by RECIST 1.1.
Lesions in previously irradiated areas should not be selected as
target lesion, unless treatment was = 3 months prior, and there
has been demonstrated disease progression in the lesion
• At least 1 resectable target lesion to generate TIL of a minimum
1.5 cm in diameter post-resection; surgical removal with minimal
morbidity (defined as any procedure for which expected
hospitalization is = 3 days)
b. Patients must be = 18 years and = 70 years of age at the time of
consent. Enrollment of patients > 70 years of age may be allowed
after consultation with the Medical Monitor
c. Patients must have an Eastern Cooperative Oncology Group (ECOG)
performance status of 0 or 1 and an estimated life expectancy of
= 3 months
d. In the opinion of the Investigator, patient must be able to complete all
study-required procedures
e. Patients of childbearing potential or their partners of childbearing
potential must be willing to practice an approved method of birth
control during treatment and for 12 months after receiving last
protocol-related therapy
Approved methods of birth control are as follows:
• Combined (estrogen and progestogen containing) hormonal birth
control associated with inhibition of ovulation: oral; intravaginal;
transdermal
• Progestogen-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.
f. Patients must have the following hematologic parameters:
• Absolute neutrophil count (ANC) = 1000/mm3
• Hemoglobin = 9.0 g/dL
• Platelet count = 100,000/mm3
g. 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
• An estimated creatinine clearance (eClCr) = 40 mL/min using the
Cockcroft-Gault formula at Screening
• Total bilirubin = 2 mg/dL
o Patients with Gilbert’s syndrome must have a total
bilirubin = 3 mg/dL
h. Patients must be seronegative for the human immunodeficiency virus
(HIV) antibody, hepatitis B antigens, and hepatitis C antibody or
antigen
i. 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), with a washout period from
prior anticancer therapy(ies) to the start of planned NMA-LD of a
minimum duration detailed as follows:
• Targeted therapy: prior targeted therapy with a MEK/BRAF or
other-directed agent, is allowed provided the washout period is a
= 21 days or 5 half-lives, whichever is lon
a. Patients with melanoma of uveal/ocular origin
b. Patients who have received an organ allograft or prior cell transfer
therapy that included a nonmyeloablative or myeloablative
chemotherapy regimen (not applicable for patients in the retreatment
Cohort 3)
c. 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 after discussion with the Medical
Monitor, and must be stable for = 2 weeks prior to the start of
NMA-LD
d. Patients who are pregnant or breastfeeding
e. Patients who are on a systemic steroid therapy at a dose of > 10 mg
of prednisone or equivalent per day
• A short course of higher-dose steroid therapy is allowed in cases
of exacerbation of known disease or for treatments of new acute
symptoms
f. Patients who have active medical illness(es) that in the opinion of the
Investigator would pose increased risk for study participation that
may include active systemic infections, such as syphilis, or any other
infections requiring antibiotics, coagulation disorders, or other active
major medical illnesses of the cardiovascular, respiratory, or immune
system
g. Patients who have any form of primary immunodeficiency (such as
severe combined immunodeficiency disease [SCID] or acquired
immunodeficiency syndrome [AIDS])
h. Patients who have a history of hypersensitivity to any component or
excipient of the TIL therapy and other study drugs:
• NMA-LD (cyclophosphamide, mesna, and fludarabine)
• IL-2
• Antibiotics of the aminoglycoside group (ie, streptomycin,
gentamicin)
• Any component of the TIL infusion product formulation
including dimethyl sulfoxide [DMSO], human serum albumin
[HSA], IL-2, and dextran-40
i. Patients who have a left ventricular ejection fraction (LVEF) < 45%
or New York Heart Association (NYHA) functional classification
> Class 1 at Screening. All patients must have echocardiogram
(ECHO) or multiple gated acquisition scan (MUGA) at Screening.
For patients = 60 years or patients who have a history of ischemic
heart disease, chest pain, or clinically significant atrial and/or
ventricular arrhythmias, a cardiac stress tests must be performed
showing LVEF =45%, and if any wall movement abnormalities,
they must be reversible.
j. Patients who have obstructive or restrictive pulmonary disease and
have a documented FEV1 (forced expiratory volume in 1 second) of = 60%
k. 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 nonmelanoma
skin cancer that has been adequately treated)
l. Patients who have been shown to be BRAF mutation positive (V600),
but have not received prior systemic therapy with a BRAF-directed
kinase inhibitor
m. Patients who have received a live or attenuated vaccine within
28 days of the start of NMA-LD
n. Patients whose cancer requires immediate attention or who would
otherwise suffer a disadvantage by participating in this trial
o. 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of LN-144 in patients with metastatic melanoma using the ORR as assessed by the Investigator per RECIST 1.1;Secondary Objective: - To evaluate the efficacy endpoints of duration of response (DOR), disease control rate (DCR), and progression free survival (PFS) as assessed by the Investigator per RECIST 1.1<br>- To further evaluate efficacy of LN-144 therapy in patients with metastatic melanoma by assessing ORR, DOR, DCR, and PFS as assessed by the Independent Review Committee (IRC) per RECIST 1.1<br>- To evaluate overall survival (OS)<br>- To characterize the safety profile of LN-144 in patients with metastatic melanoma;Primary end point(s): Objective response rate (ORR) as assessed by the Investigator per RECIST 1.1 criteria;Timepoint(s) of evaluation of this end point: After last patient in Cohort 2 reach the 6-month tumor assessment, and final analysis at end of 2-year post-treatment follow up.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): •DOR, DCR and PFS per RECIST 1.1, as assessed by the BIRC<br>•ORR, DOR, DCR and PFS per RECIST 1.1, as assessed by the Investigator<br>•Overall survival (OS)<br>•Incidence, severity, seriousness, relationship to study treatment, and characteristics of treatment-emergent adverse events (TEAEs), including<br>AEs leading to early discontinuation from treatment or withdrawal from the Assessment Period, and AEs resulting in deaths;Timepoint(s) of evaluation of this end point: Every 6 weeks for 6 months, then every 3 months for a maximum of 54 months;<br>OS: Time Frame: Until death or up to 60 months; adverse events: Time Frame: Maximum 60 months