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The purpose of this research study is to test the safety and effectiveness of a tumor-infiltrating lymphocyte (TIL) cellular therapy, also called LN-145 or lifileucel, and chemotherapy in combination with Interleukin-2 (IL-2) to find out what effects, if any, the combination has on participants with Cutaneous squamous cell carcinoma (CSCC) or Merkel Cell Carcinoma (MCC) who were previously treated with immunotherapy.
The names of the study interventions involved in this study are:
Full description
This is an open-label, multi-cohort, non-randomized, single-center, phase 2 clinical trial testing the safety and effectiveness of a tumor-infiltrating lymphocyte (TIL) cellular therapy, also called LN-145 or lifileucel, and chemotherapy in combination with Interleukin-2 (IL-2) to find out what effects, if any, the combination has on participants with Cutaneous squamous cell carcinoma (CSCC) or Merkel Cell Carcinoma (MCC) who were previously treated with immunotherapy.
Lymphocytes are a part of the immune system that help fight infection and prevent and fight cancers. TIL cells are grown in a specialized laboratory with the goal of making more of them so that the TIL cells better recognize and kill cancer cells when administered again into the body.
The U.S. Food and Drug Administration (FDA) has approved Fludarabine and Cyclophosphamide as standard-of-care lymphodepleting chemotherapy medications.
The U.S. FDA has not approved TIL therapy, Lifileucel plus IL-2, for CSCC or MCC, but it has been approved for the treatment of another type of skin cancer, advanced melanoma.
The research study procedures include screening for eligibility, in-clinic visits, blood tests, urine tests, Computerized Tomography (CT) scans, Magnetic Resonance Imaging (MRI) scans, or Positron Emission (PET) scans, X-rays, electrocardiograms (ECGs), echocardiograms (ECHOs), Cardiac stress test, lung function test, bone marrow biopsies and aspirations.
It is expected that about 14 people will take part in this research study.
Iovance Biotherapeutics, Inc. is supporting this research study by providing the study therapy, IL-2 and funding.
Enrollment
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Volunteers
Inclusion criteria
Provide written informed consent, which includes understanding that there may be a need for intensive supportive care measures during the study and assessing willingness to undergo such measures, and written authorization for use and disclosure of protected health information.
Patients must be ≥ than 18 years of age at the time of signing the informed consent form.
Patients must have histologically or pathologically confirmed diagnosis of CSCC or MCC. Note: Mixed histology is allowed. Note: Neuroendocrine cancer that is clinically considered to be related to a cutaneous primary (MCC) or induced by sun damage (per investigator assessment) is allowed.
Patients must have unresectable, recurrent, or metastatic disease.
Patients must have a documented radiographic or clinical disease progression after treatment with ICI (including anti-PD-1 and anti-PD-L1) if it is used in the palliative setting. In patients who received ICI in the neoadjuvant or adjuvant setting, recurrence should have occurred within 6 months from the last treatment with ICI.
Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 in the investigator's opinion (Appendix B).
Patients must have at least 1 resectable lesion (or aggregate lesions) with an expected minimum of 1.5 cm diameter in the short axis for TIL production. Note: If a lesion that is considered for TIL harvest is within a previously irradiated field, the lesion must have demonstrated radiographic or clinical progression prior to harvest, and the irradiation must have been completed at least 6 months prior to enrollment.
Patients must be expected to have at least 1 remaining measurable lesion as defined by RECIST v1.1 or evaluable (radiographically or on clinical examination) following tumor harvest for TIL manufacturing and production that is documented at screening with the following considerations:
Patients must have the following hematologic parameters:
Patients must have an adequate organ function with the following laboratory test values:
Patients must have a left ventricular ejection fraction (LVEF) ≥ 45% and be New York Heart Association (NYHA) Class 1 or 2. A cardiac stress test is required for patients who have significant ischemic heart disease, or clinically significant unstable arrythmias; the cardiac stress test must demonstrate no irreversible wall movement abnormality. Patients with an abnormal cardiac stress test may be enrolled if they have adequate ejection fraction and cardiology clearance.
Patients must have adequate pulmonary function within 2 months from enrollment.
Patients require pulmonary function testing (PFT) if they have any of the following:
Post-bronchodilator required pulmonary test results:
Forced expiratory volume (FEV1)/ forced vital capacity (FVC) > 70%. Or
FEV1 > 50% of predicted normal value. Note: If a patient is unable to perform reliable spirometry due to abnormal upper airway anatomy (i.e., tracheostomy), a 6-minute walk test may be used to assess pulmonary function. Patients must be able to walk a distance at least 80% of predicted for age and sex with no evidence of hypoxia at any point during the test (i.e., saturation of peripheral oxygen [SpO2] must remain ≥ 89%).
Approved methods of birth control include:
oral, injectable, implantable.
Exclusion criteria
Have a history of allogenic organ transplant.
Have symptomatic untreated brain metastases. Patients with brain metastases may be enrolled with the following considerations:
Require systemic steroid therapy >10 mg/day prednisone or its equivalent. Patient receiving steroids as replacement therapy for adrenocortical insufficiency are not excluded.
Have evidence of any active viral, bacterial, or fungal infection requiring ongoing systemic treatment.
Are pregnant or breastfeeding. Female patients of childbearing potential must have a negative beta human chorionic gonadotropin (B-HCG) test at Screening (Appendix C).
Have active medical illness that in the opinion of the investigator would pose increased risk for study participation, such as systemic infections, coagulation disorders, or other active major medical illnesses of the cardiovascular, respiratory, or immune system.
Have received a live or attenuated vaccination within 28 days prior to the start of NMALD.
Have any form of primary immunodeficiency (e.g., severe combined immunodeficiency disease [SCID] or acquired immune deficiency syndrome [AIDS]).
Have a history of allogenic stem cell transplant, or active hematological malignancy (such as chronic lymphocytic leukemia or lymphoma).
Have 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 the autologous TIL product formulation including, but not limited to, any of the following:
Have had another primary malignancy within the previous 1 year (except for malignancies that do not require treatment or have been curatively treated, and do not pose a significant risk of recurrence including, but not limited to in situ carcinoma of the cervix, early stage skin cancer, including non-melanoma skin cancer; ductal carcinoma in situ (DCIS) or lobular carcinoma in the situ (LCIS) of the breast; intraductal carcinoma of the breast that has been treated with curative intent including patients who are on adjuvant hormonal treatment, prostate cancer with Gleason score ≤ to 6; or superficial bladder cancer).
Primary purpose
Allocation
Interventional model
Masking
14 participants in 2 patient groups
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Central trial contact
Karam Khaddour, MD
Data sourced from clinicaltrials.gov
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