TIL Therapy in cSCC and MCC

NCT07288073 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 25-394
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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)

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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.

  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).

  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.

  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.

Secondary Outcomes (4)

• objective response rate (ORR)

  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)

  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)

  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)

  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.

Study Arms (2)

Cohort A: CSCC Autologous TIL Therapy

EXPERIMENTAL

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

Biological: LN-145; Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Interleukin-2

Cohort B: MCC Autologous TIL Therapy

EXPERIMENTAL

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

Biological: LN-145; Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Interleukin-2

Interventions

LN-145 BIOLOGICAL

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

Also known as: Autologous Tumor Infiltrating Lymphocytes

Cohort A: CSCC Autologous TIL Therapy; Cohort B: MCC Autologous TIL Therapy

Cyclophosphamide DRUG

Antineoplastic drug, multi-dose vial, per institutional standards

Also known as: Cytoxan, Cyclophosphamide-OE

Cohort A: CSCC Autologous TIL Therapy; Cohort B: MCC Autologous TIL Therapy

Fludarabine DRUG

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

Also known as: Fludarabine Phosphate

Cohort A: CSCC Autologous TIL Therapy; Cohort B: MCC Autologous TIL Therapy

Interleukin-2 BIOLOGICAL

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

Also known as: Aldesleukin, Proleukin, IL-2

Cohort A: CSCC Autologous TIL Therapy; Cohort B: MCC Autologous TIL Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• Iovance Biotherapeutics, Inc.: collaborator
• Karam Khaddour, MD, MS: lead

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Merkel Cell; Skin Neoplasms

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Interleukin-2; aldesleukin

Condition Hierarchy (Ancestors)

Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• Karam Khaddour, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karam Khaddour, MD

CONTACT

617-632-6571; karam_khaddour@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: December 15, 2025
• First Posted: December 17, 2025
• Study Start: February 10, 2026
• Primary Completion (Estimated): September 29, 2028
• Study Completion (Estimated): June 29, 2029
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (1)