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)
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.
Have a history of allogenic organ transplant.
Patients with asymptomatic brain metastases that are treated and have been stable for at least 7 days may be enrolled.
Patients with historically or recently treated brain metastases will be considered for enrollment if the patient is clinically stable for ≥ 2 weeks, and the patient does not require ongoing corticosteroid treatment (>10 mg/day prednisone or its equivalent).
Patients who undergo tumor harvest prior to disease progression and develop symptomatic brain metastases after tumor harvest should have receive appropriate treatment for ≥ 2 weeks and not require corticosteroids (>10 mg/day or its equivalent) at the start of NMA-LD (Day -5).
Parallel
LN-145
Biological/VaccineAutologous tumor-infiltrating lymphocytes via intravenous (into the vein) infusion per protocol
Cyclophosphamide
DrugAntineoplastic drug, multi-dose vial, per institutional standards
Fludarabine
DrugNucleotide metabolic inhibitor, single-use vial, via intravenous infusion per institutional standards
Interleukin-2
Biological/VaccineRecombinant, human glycoprotein, single-use vial, via intravenous infusion per protocol
Tumor-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.
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).
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.
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.
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.
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.
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.
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Karam Khaddour, MD, MS
Lead sponsor
Dana-Farber Cancer Institute
Sponsor institution
Iovance Biotherapeutics, Inc.
Collaborator
