TIL Therapy in cSCC and MCC

NCT ID: NCT07288073

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

14 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-31

Study Completion Date

2029-06-29

Brief Summary

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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:

* 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)

Detailed Description

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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.

Conditions

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Cutaneous Squamous Cell Carcinoma Merkel Cell Carcinoma Metastatic Cutaneous Squamous Cell Carcinoma Skin Cancer

Keywords

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Cutaneous Squamous Cell Carcinoma Merkel Cell Carcinoma Metastatic Cutaneous Squamous Cell Carcinoma Skin Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort A: CSCC Autologous TIL Therapy

10 participants with CSCC will complete:

* Screening visit
* Surgical procedure to collect tissue, called TIL harvest
* Baseline visit
* Days -5 through -1: Predetermined dose of Lymphodepleting Chemotherapy, Fludarabine, 1x daily
* Days -5 and -4: Predetermined dose of Lymphodepleting Chemotherapy, Cyclophosphamide, 1x daily
* Day 0: TIL infusion
* Days 0, 1, 2, 3, 4, and 14: Predetermined dose of IL-2 1x daily for up to 6 doses
* Imaging at weeks 6 and 12
* End of treatment visit with imaging
* Long term follow up every 3 months for up to 3 years

Group Type EXPERIMENTAL

LN-145

Intervention Type BIOLOGICAL

Autologous tumor-infiltrating lymphocytes via intravenous (into the vein) infusion per protocol

Cyclophosphamide

Intervention Type DRUG

Antineoplastic drug, multi-dose vial, per institutional standards

Fludarabine

Intervention Type DRUG

Nucleotide metabolic inhibitor, single-use vial, via intravenous infusion per institutional standards

Interleukin-2

Intervention Type BIOLOGICAL

Recombinant, human glycoprotein, single-use vial, via intravenous infusion per protocol

Cohort B: MCC Autologous TIL Therapy

4 participants with MCC will complete:

* Screening visit
* Surgical procedure to collect tissue, called TIL harvest
* Baseline visit
* Days -5 through -1: Predetermined dose of Lymphodepleting Chemotherapy, Fludarabine, 1x daily
* Days -5 and -4: Predetermined dose of Lymphodepleting Chemotherapy, Cyclophosphamide, 1x daily
* Day 0: TILs infusion
* Days 0, 1, 2, 3, 4, and 14: Predetermined dose of IL-2 1x daily for up to 6 doses
* Imaging at weeks 6 and 12
* End of treatment visit with imaging
* Long term follow up every 3 months for up to 3 years

Group Type EXPERIMENTAL

LN-145

Intervention Type BIOLOGICAL

Autologous tumor-infiltrating lymphocytes via intravenous (into the vein) infusion per protocol

Cyclophosphamide

Intervention Type DRUG

Antineoplastic drug, multi-dose vial, per institutional standards

Fludarabine

Intervention Type DRUG

Nucleotide metabolic inhibitor, single-use vial, via intravenous infusion per institutional standards

Interleukin-2

Intervention Type BIOLOGICAL

Recombinant, human glycoprotein, single-use vial, via intravenous infusion per protocol

Interventions

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LN-145

Autologous tumor-infiltrating lymphocytes via intravenous (into the vein) infusion per protocol

Intervention Type BIOLOGICAL

Cyclophosphamide

Antineoplastic drug, multi-dose vial, per institutional standards

Intervention Type DRUG

Fludarabine

Nucleotide metabolic inhibitor, single-use vial, via intravenous infusion per institutional standards

Intervention Type DRUG

Interleukin-2

Recombinant, human glycoprotein, single-use vial, via intravenous infusion per protocol

Intervention Type BIOLOGICAL

Other Intervention Names

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Autologous Tumor Infiltrating Lymphocytes Cytoxan Cyclophosphamide-OE Fludarabine Phosphate Aldesleukin Proleukin IL-2

Eligibility Criteria

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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:

* Lesions in a previously irradiated areas should not be selected as target lesions unless progression has been demonstrated in those lesions and the irradiation has been completed at least 6 months prior to enrollment.
* Patients who have only one site of disease may be enrolled if they have a lesion th can be partially resected for TIL harvest, and the remaining portion of the lesion is measurable or evaluable.
* Patients must have the following hematologic parameters:

* Absolute neutrophil count (ANC) ≥ 1000/mm3
* Hemoglobin ≥ 8.0 g/dL and have not received transfusion of packed red blood cells within 7 days.
* Platelet count ≥ 100,000/mm3
* Patients must have an adequate organ function with the following laboratory test values:

* Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal (ULN); and for patients with liver metastases ≤ to 5 times ULN.
* Total bilirubin ≤ 2 mg/dL; patients with Gilbert's Syndrome ≤ to 3 mg/dL.
* Estimated creatinine clearance (eCrCl) ≥ 40 mL/min using the Cockcroft-Gault formula at Screening.
* 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:

* History of cigarette smoking of ≥ 20 pack-years
* Ceased smoking within the past 2 years or still smoking.
* History of chronic obstructive pulmonary disease (COPD)
* Any signs or symptoms of significant respiratory dysfunction.

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%).

* Patients must have completed or discontinued systemic therapy ≥ 21 days prior to tumor harvest. Note: Patients are allowed to have palliative radiation or systemic therapy after tumor harvest and before NMA-LD but there should be at least 7 days between discontinuation of palliative treatment and start of NMA-LD.
* Patients must have recovered from all prior anticancer TRAEs to Grade ≤ 1 (per CTCAE v5.0) with the exceptions of vitiligo, alopecia or neuropathy. Patients with irreversible toxicity that are properly managed (such as with endocrinopathy treatment with hormone replacement therapy) may qualify for the study regardless of grade of TRAEs.
* 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 (Appendix C). Additionally, males may not donate sperm and females may not donate eggs during the required contraception period.

Approved methods of birth control include:

* Combined (estrogen- and progesterone- containing) hormonal birth control associated with inhibition of ovulation: oral, intravaginal, transdermal.
* Progesterone-only hormonal birth control associated with inhibition of ovulation:

oral, injectable, implantable.

* Intrauterine device (IUD)
* Intrauterine hormone-releasing system (IUS)
* Bilateral tubal occlusion
* Vasectomy
* True absolute sexual abstinence when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar ovulation, symptothermal, post-ovulation methods) is not acceptable.

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:

* 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).
* 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:

* NMA-LD (cyclophosphamide, mesna, and fludarabine)
* Proleukin, aldesleukin, IL-2
* Antibiotics of the aminoglycoside group. These patients may be eligible if current hypersensitivity has been excluded.
* Any component of the TIL product formulation, including dimethyl sulfoxide (DMSO), human serum albumin (HSA), IL-2, or dextran-40
* 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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Iovance Biotherapeutics, Inc.

INDUSTRY

Sponsor Role collaborator

Karam Khaddour

OTHER

Sponsor Role lead

Responsible Party

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Karam Khaddour

Sponsor-Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Karam Khaddour, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

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Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Countries

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United States

Central Contacts

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Karam Khaddour, MD

Role: CONTACT

Phone: 617-632-6571

Email: [email protected]

Facility Contacts

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Karam Khaddour, MD

Role: primary

Other Identifiers

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25-394

Identifier Type: -

Identifier Source: org_study_id