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: 20.0 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-001608-12-ES
- 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
- 36
1. All patients must have a histologically confirmed unresectable or metastatic melanoma (Cohort 1), recurrent or metastatic squamous cell carcinoma of the head and neck (Cohort 2, primary tumor histologic diagnosis confirmation required via pathology report), or recurrent or metastatic non-small cell lung cancer (Cohort 3).
2. Cohort 1 and Cohort 2 only: patients who have not received prior immunotherapy, including checkpoint inhibitors.With the excluded prior therapies cited, patients may have received from 1 to 3 prior systemic anticancer therapies:
• In Cohort 1: Patients with unresectable or metastatic melanoma; if BRAF mutation-positive, patients may have received a BRAF inhibitor.
• In Cohort 2: Patients with unresectable or metastatic HNSCC. Those who may have received initial chemo-radiotherapy are allowed.
3. Cohort 3 only: Patients with Stage III or Stage IV NSCLC (squamous, nonsquamous, adenocarcinoma, or large cell carcinoma) who have received from 1 to 3 prior systemic anticancer therapies including checkpoint inhibitors in the locally advanced or metastatic setting.
4. Patients must have at least 1 resectable lesion of a minimum 1.5 cm in diameter postresection 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 it 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 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.
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 their partners of childbearing potential must be willing to practice an approved method of 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. 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 detailed below prior to the first study treatment (ie, start of NMA LD)
• Targeted therapy: prior targeted therapy with EGFR, MEK, BRAF, A
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. Note: this criterion is not applicable for patients undergoing retreatment with TIL LN-144/LN-145.
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 NMA-LD the patient is clinically stable for =2 weeks, there are no new brain lesions via magnetic resonance imaging (MRI) post-treatment, and the patient does not require corticosteroid treatment >10 mg prednisone or equivalent per day.
4. Patients who are on a systemic steroid therapy at a dose of >10 mg of prednisone or equivalent per day.
• Short course of higher-dose steroid therapy is allowed in cases of exacerbation of a known disease or for treatment of new acute symptoms not related to brain metastases.
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 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 NMA-LD.
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:
• NMA-LD (cyclophosphamide, mesna, and fludarabine);
• Proleukin®, aldesleukin, IL-2;
• Antibiotics of the aminoglycoside group (ie, streptomycin, gentamicin);
• Any component of the TIL product formulation including dimethyl sulfoxide [DMSO], human serum albumin [HSA], IL-2, and dextran-40; or
• Pembrolizumab.
11. Patients who have a left ventricular ejection fraction (LVEF) <45% or who are New York Heart Association (NYHA) Class II or higher. A cardiac stress test demonstrating any irr
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