A clinical study to investigate if the investigational products, called LN-144, LN-145 and LN-145-S1 (also known as Tumour Infiltrating Lymphocytes), are safe and beneficial in the treatment of patients with Solid Tumours.
- Conditions
- Solid Tumours including advanced unresectable or metastatic melanoma (MM), advanced squamous cell carcinoma of the head and neck (HNSCC) and non-small cell lung cancer (NSCLC)MedDRA version: 21.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10027481Term: Metastatic melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-001608-12-GR
- Lead Sponsor
- Iovance Biotherapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 135
1. All patients must have a histologically or pathologically confirmed diagnosis of malignancy:
- Unresectable or metastatic melanoma Stage IIIC or Stage IV (Cohorts
1A and 1C)
- Advanced, recurrent or metastatic HNSCC (Cohort 2A)
- Stage III or Stage IV NSCLC (Cohorts 3A,3B and 3C)
2. Cohorts 1A, 2A, and 3A: If previously treated, patients must have
progressed on or after most recent therapy and must not have received
CPIs as part of one of the counted lines of prior therapy. Patients must
have radiologically documented disease progression while receiving or
after the completion of the most recent prior
treatment. Patients may have received up to 3 prior systemic anticancer
therapies, (except for Cohort 3A, where patients may have received up
to 4 prior systemic therapies)
3. Cohorts 1C, 3B, and 3C: Unresectable or metastatic melanoma patients in Cohorts 1C
must have previously received systemic therapy with a PD-1 blocking
antibody. NSCLC patients in Cohort 3B must have previously received
systemic therapy with any CPI (except for those patients with known
oncogene drivers who have mutations that are sensitive to targeted
therapies) as part of 1-3 prior lines of therapy. NSCLC patients in Cohort
3C must have received prior systemic therapy with an approved
monotherapy CPI as their single prior line of systemic therapy.
4. Patients must have at least 1 resectable lesion (or aggregate lesions)
of a minimum 1.5 cm in diameter post-resection for TIL investigational
product production. It is encouraged that tumor tissue be obtained from
multiple and diverse metastatic lesions, as long as the surgical resection
does not pose additional risks to the patient.
5. Patients must have a remaining measurable disease as defined by
RECIST 1.1 following tumor resection for TIL manufacturing
6. Patients must be =18 years at the time of consent in all cohorts.
Enrollment of patients > 70 years of age may be allowed after
consultation with the Medical Monitor.
7. Patients must have an Eastern Cooperative Oncology Group
performance status of 0 or 1, and an estimated life expectancy of =6
months in the opinion of the Investigator.
8. Patients of childbearing potential or those with partners of
childbearing potential must be willing to practice an approved method of
highly effective birth control during treatment and for 12 months after
receiving all protocol-related therapy
9. Patients must have the following hematologic parameters
independent of transfusion and/or blood product support for at least 5
days prior to laboratory testing:
• Absolute neutrophil count =1000/mm3
• Hemoglobin =9.0 g/dL
• Platelet count =100,000/mm3
10. Patients must have adequate organ function:
• ALT/ SGPT and AST/SGOT =3 times the upper limit of normal, patients
with liver metastasis =5 times ULN
• An estimated creatinine clearance =40 mL/min at Screening using the
Cockcroft-Gault formula
• Total bilirubin =2 mg/dL
• Patients with Gilbert's Syndrome must have a total bilirubin =3 mg/dL
11. Patients must be seronegative for HIV (HIV1 and HIV2). Patients
with positive serology for hepatitis B virus surface antigen, hepatitis B
core antibody, or hepatitis C virus indicating acute or chronic infection
may be enrolled if the viral load by PCR is undetectable with/without
active treatment
12. Patients must have a washout period from prior anticancer
therapy(ies) of a minimum duration as defined in the protocol (ie, start
of NMA LD or pembrolizumab or ipilimumab/nivolumab)
13. Patien
1.Patients with melanoma of uveal/ocular origin
2.Patients who have received an organ allograft or prior cell transfer
therapy that included a nonmyeloablative or myeloablative
chemotherapy regimen within the past 20 years. Note: This criterion is
applicable for patients undergoing retreatment with TIL, with the
exception that they will have had a prior NMA-LD regimen with their
prior TIL treatment.
3.Patients with symptomatic and/or untreated brain metastases.
•Patients with historically (prior to consenting for study participation)
treated brain metastases will be considered for enrollment if the patient
is clinically stable for = 2 weeks, there are no new brain lesions via
screening magnetic resonance imaging (MRI), and the patient does not
require ongoing corticosteroid treatment. If there are progressive or
new brain metastases on screening MRI, the patient should first receive
treatment for them prior to consideration of enrollment. Follow up
imaging post-treatment is not required to enroll.
• Patients with recently (during screening period or within 28 days prior
to enrollment) treated brain metastases may be considered for
enrollment if the patient is asymptomatic, clinically stable for = 2 weeks
and not requiring corticosteroid by the end of the screening period.
Follow up imaging post-treatment is not required to enroll. Medical
monitor approval is required.
4.Patients who are on systemic steroid therapy > 10 mg/day of
prednisone or other steroid equivalent..
5.Patients who are pregnant or breastfeeding.
6.Patients who have an active medical illness(es), which in the opinion
of the Investigator, would pose increased risks for study participation;
such as systemic infections (eg, syphilis or any other infection requiring
antibiotics), coagulation disorders, or other active major medical
illnesses of the cardiovascular, respiratory, or immune systems.
7. Cohort 1A, 2A, 3A, and 3C patients may not have a medical history of
autoimmune disorders (including pneumonitis) requiring treatment or
active management. The following are exceptions to this criterion:
•Patients with vitiligo or alopecia;
•Patients with thyroid dysfunction (eg, following Hashimoto syndrome)
stable on hormone replacement;
•Any chronic skin condition that does not require systemic therapy; or
•Patients with celiac disease controlled by diet alone.
8.Patients who have received a live or attenuated vaccination within 28
days prior to the start of treatment.
9.Patients who have any form of primary immunodeficiency (such as
severe combined immunodeficiency disease [SCID] and acquired
immune deficiency syndrome [AIDS]).
10.Patients with a history of hypersensitivity to any component of the
study drugs. TIL should not be administered to patients with a known
hypersensitivity to any component of TIL product formulation including,
but not limited to any of the following:
•NMA-LD (cyclophosphamide, mesna, and fludarabine)
•Proleukin®, aldesleukin, IL-2
•Antibiotics of the aminoglycoside group (ie, streptomycin, gentamicin
[excluding those who are skin-test negative for gentamicin
hypersensitivity])
•Any component of the TIL product formulation including dimethyl
sulfoxide [DMSO], HSA, IL-2, and dextran-40
•Pembrolizumab
•Ipilimumab
•Nivolumab
11.Patients who have a left ventricular ejection fraction (LVEF) <45% or
who are New York Heart Association Class II or higher. A cardiac stress
test demonstrating any irreversible wall movement abnormality in any
patients =60 year
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method