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: * Tumor Infiltrating Lymphocytes (a type of cellular therapy) * Fludarabine and Cyclophosphamide (types of standard of care chemotherapy drugs) * Interleukin-2 (a type of recombinant, human glycoprotein)
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
14
Autologous tumor-infiltrating lymphocytes via intravenous (into the vein) infusion per protocol
Antineoplastic drug, multi-dose vial, per institutional standards
Nucleotide metabolic inhibitor, single-use vial, via intravenous infusion per institutional standards
Recombinant, human glycoprotein, single-use vial, via intravenous infusion per protocol
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITINGTumor-infiltrating lymphocyte (TIL) Production
Tumor-infiltrating lymphocyte (TIL) production is defined by the successful tumor harvest that leads to a manufacturing of a TIL product that contains ≥ 1 x 10\^9 cells.
Time frame: TIL infusion will be performed at day 0 of the study.
Tumor-infiltrating lymphocyte (TIL) Administration
TIL administration is defined by the administration of NMA-LD, complete infusion of TIL therapy and at least 1 dose of interleukin-2 (IL-2).
Time frame: Evaluated up to 24 hours from TIL infusion (day 0) as IL-2 first dose will be administered with in 12-24 hours from TIL infusion.
Incidence of Grade ≥3 treatment-emergent adverse events (TEAEs)
TEAEs will determined on the Common Toxicity Criteria for Adverse Events Version 5.0 (CTCAEv5) as reported on case report forms.
Time frame: Adverse events will be collected until 30 days post treatments. The study does not have a fixed treatment duration as defined in the protocol section 5.5.
objective response rate (ORR)
ORR is defined as the proportion of participants receiving TIL therapy who achieve a best response of either complete response (CR) or partial response (PR) based on RECIST 1.1. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Time frame: Participants will be followed throughout the course of the trials for 3 years from the time of the end of treatment visit. The study does not have a fixed treatment duration as defined in the protocol section 5.5.
progression-free survival (PFS)
PFS based on Kaplan-Meier method is defined as the time from study enrollment to the earlier of disease progression (RECIST 1.1) or death. The follow-up of participants who neither progress nor die will be censored at the date of the last follow-up. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.
Time frame: Participants will be followed for 3 years from the end-of-treatment visit. The study does not have a fixed treatment duration, as specified in Section 5.5 of the protocol.
duration of response (DoR)
DOR is defined as the time from the first documentation of an objective response, either complete response (CR) or partial response (PR), to the time of disease progression or death, whichever occurs first. The follow-up of participants who have neither progressed nor died will be censored at the date of last follow-up. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.
Time frame: Participants will be followed for 3 years from the end-of-treatment visit. The study does not have a fixed treatment duration, as specified in Section 5.5 of the protocol.
overall survival (OS)
Overall survival (OS) based on the Kaplan-Meier method is defined as the time from randomization to death. Participants alive are censored at the last date of contact (including lost-to-follow-up) or at the date of withdrawal of consent, if relevant.
Time frame: Participants will be followed for 3 years from the end-of-treatment visit. The study does not have a fixed treatment duration, as specified in Section 5.5 of the protocol.
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