A clinical study to investigate if the investigational products, called LN-144 and LN-145 (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-GB
- 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
- 48
1. All patients must have a histologically or pathologically confirmed diagnosis of malignancy:
- Unresectable or metastatic melanoma (Cohort 1A)
- Advanced, recurrent or metastatic squamous cell carcinoma of the head and neck (Cohort 2A)
- Stage III or Stage IV NSCLC (Cohorts 3A and 3B)
2. Cohorts 1A, 2A, and 3A may have received up to 3 prior systemic anticancer therapies, specifically:
- In Cohort 1A: Patients with unresectable or metastatic melanoma; if BRAF mutation-positive, patients may have received a BRAF inhibitor.
- In Cohort 2A: Patients with unresectable or metastatic HNSCC. Those who may have received initial chemo-radiotherapy are allowed.
- Cohort 3A only: Patients with Stage III or Stage IV NSCLC (squamous, nonsquamous, adenocarcinoma, or large cell carcinoma) and who are immunotherapy naive and progressed after = 3 lines of prior systemic therapy in the locally advanced or metastatic setting.
3. Cohort 3B only: Patients with Stage III or Stage IV NSCLC (squamous, nonsquamous, adenocarcinoma, or large cell carcinoma) who have previously received systemic therapy with CPIs (eg, anti-PD-1/anti-PDL1) as part of = 3 prior lines of systemic therapy. Patients must have
radiographically confirmed progression on or after most recent therapy.
4. Patients must have at least 1 resectable lesion (or aggregate lesions) of a minimum 1.5 cm in diameter 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.
7. Patients must have an Eastern Cooperative Oncology Group performance status of 0 or 1, and an estimated life expectancy of =3 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:
•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 using the Cockcroft Gault formula at Screening;
•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,
• prior targeted therapy with EGFR, MEK, BRAF, ALK, ROS1 or other-targeted agents is allowed provided the washout is a minimum of 14 days prior to the start of treatment;
•Chemotherapy: adjuvant, neoadjuvant or definitive chemotherapy/chemoradiation is allowed provided the washout is a minimum of 21 days prior to the start of treatment
• Immunotherapy for Cohort 3B only;
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 LN-144/ LN145, 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 definitively-treated brain metastases will be considered for enrollment after discussion with Medical Monitor; if, prior to the start of treatment the patient is clinically stable for =2 weeks, there are no new brain lesions via magnetic resonance imaging (MRI) posttreatment, and the patient does not require ongoing corticosteroid treatment.
4. Patients who are on a systemic steroid therapy within 21 days of enrollment.
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. Patients may not have active or prior documented autoimmune or inflammatory disorders (including pneumonitis, inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:
•Patients with vitiligo or alopecia;
•Patients with hypothyroidism (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. LN-144/LN-145 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
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 years of age or in patients who have a history of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias.
•Patients with an abnormal cardiac stress test may be enrolled if they have adequate ejection fraction and cardiology clearance with approval of the Sponsor's Medical Mo
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