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: 20.0 Level: PT Classification code 10027480 Term: Metastatic malignant melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-000760-15-FR
- Lead Sponsor
- Iovance Biotherapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 60
a. Patients with unresectable metastatic melanoma (Stage IIIc or
Stage IV) who progressed following =1 line of prior systemic therapy,
including immune checkpoint inhibitor (e.g., anti-PD-1), and if BRAF
mutation-positive, after BRAF inhibitor systemic therapy
- At least one measurable target lesion as defined by RECIST version
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 progression in the lesion
- At least one resectable lesion to generate TILs of a minimum 1.5 cm
in diameter post-resection
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 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 4 months after receiving all protocol
related therapy
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 ALT/SGPT and AST/SGOT < 3 times the upper limit of normal
ULN), patients with liver metastasis < 5 times ULN
- an estimated creatinine clearance (eCCr) = 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 HIV antibody, hepatitis B
antigen, and hepatitis C antibody or antigen
i. Patients must have recovered from all prior therapy-related AEs to
Grade 1 or less (per CTCAE v4.03), except for alopecia or vitiligo, prior
to enrollment (tumor resection)
- A minimal washout period of 4 weeks is required prior to enrollment (tumor resection)
- Palliative radiation therapy is permitted between biopsy and
nonmyeloablative lymphodepletion if it does not involve lesions being
selected as target or non-target lesions
- Patients may undergo pre-planned procedures if within 2-3 weeks
prior to the start of nonmyeloablative lymphodepletion
j. Patients with documented Grade 2 or greater 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 start of nonmyeloablative lymphodepletion
a. Patients with melanoma of uveal/ocular origin
b. Patients who have received 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, will be considered for enrollment after discussion with Medical Monitor, and must be stable for 2-4 weeks prior to the start of treatment nonmyeloablative lymphodepletion)
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, such as systemic 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 and AIDS)
h. Patients who have a history of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or IL-2
i. Patients who have a left ventricular ejection fraction (LVEF) < 45% at Screening
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 non-melanoma skin cancer that has been adequately treated)
l. Patients with known allergic reaction to antibiotics of aminoglycoside group (i.e. streptomycin, gentamicin)
m. Patients who have been shown to be BRAF mutation positive (V600), but have not received prior systemic therapy with a BRAF-directed kinase inhibitor
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> Main Objective: To evaluate the efficacy of LN-144 in patients with metastatic<br> melanoma using the objective response rate (ORR)<br> ;<br> Secondary Objective: To further evaluate efficacy of LN-144 in patients with metastatic<br> melanoma such as complete response (CR) rate, duration of response<br> (DOR), disease control rate (DCR), progression-free survival (PFS), and<br> overall survival (OS)<br> To characterize the safety profile of LN-144 in patients with metastatic<br> melanoma<br> ;Primary end point(s): Objective response rate (ORR);<br> Timepoint(s) of evaluation of this end point: After last patient in Cohort 2 reach the 6-month tumor assessment,<br> and final analysis at end of 2-year post-treatment follow up.<br>
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): Complete response (CR) rate, duration of response (DOR), disease<br> control rate (DCR), progression free survival (PFS) and overall survival<br> (OS) per RECIST 1.1 criteria 2 by independent and Investigator review<br><br> Incidence, severity, seriousness, relationship to study treatment,<br> and characteristics of treatment-emergent AEs (TEAEs), including AEs<br> leading to early discontinuation from treatment or withdrawal from the study, and AEs resulting in deaths<br> ;<br> Timepoint(s) of evaluation of this end point: After last patient in Cohort 2 reach the 6-month tumor assessment,<br> and final analysis at end of 2-year post-treatment follow up.<br>