Neoadj Admin Autologous Tumor Infiltrating Lymphocytes & Pembrolizumab for Treatment of Adv Melanoma Patients

NCT05176470 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-21202NCI-2021-11063
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial tests the safety and side effects of LN-144 (Lifileucel) and pembrolizumab in treating patients with stage IIIB-D or stage IV melanoma that has spread to nearby tissue or lymph nodes. Biological therapies, such as LN-144 (Lifileucel), use substances made from living organisms that may attack specific tumor cells and stop them from growing or kill them. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving lifileucel and pembrolizumab may make the tumor smaller.

Conditions

Locally Advanced Melanoma; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Stage IV Melanoma

Keywords

Adoptive T-cell Therapy; Melanoma; Neoadjuvant; Tumor-infiltrating Lymphocytes; LN-144; Lifileucel

Outcome Measures

Primary Outcomes (2)

• Feasibility of neoadjuvant administration of MK-3475 and LN-144/Lifileucel in 3 stage IIIB-D melanoma patients (Phase 1)

  Success rate of tumor infiltrating lymphocyte (TIL) expansion from all screened eligible patients who have had tumor-involved lymph node(s) removed; percentage of all eligible patients who have completed the screening and treated with LN-144/lifileucel.

  Up to 2 years

• Incidence of grade >= 3 treatment-emergent adverse events (both immune and non-immune related) (Phase 2)

  The severity of AEs will be graded according to CTCAE version 5.0, and frequencies and percentages of patients with AEs will be tabulated by severity grade.

  Up to 2 years

Secondary Outcomes (2)

• Overall objective response rate

  Up to 2 years

• Relapse-free survival (RFS) rate

  At 24 months

Other Outcomes (5)

• Major pathologic response (MPR) rate

  Up to 2 years

• Immune correlates (as described above) with respect to response and 24-month relapse free survival, of the TIL/LN-144 + pembrolizumab neoadjuvant therapy

  Up to 2 years

• Success rate of TIL growth from tumor-involved lymph node(s)

  Up to 2 years

Study Arms (1)

Treatment (pembrolizumab, lifileucel)

EXPERIMENTAL

Patients receive pembrolizumab IV on day -14, cyclophosphamide IV QD on days -7 to -6, fludarabine IV over 30 minutes QD on days -5 to -1, and lifileucel IV infusion on day 0. Patients also receive pembrolizumab IV on day 28 and 70, and undergo surgery on day 80. MAINTENANCE: Patients receive pembrolizumab IV every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.

Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Lifileucel; Biological: Pembrolizumab; Procedure: Therapeutic Conventional Surgery

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (pembrolizumab, lifileucel)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (pembrolizumab, lifileucel)

Lifileucel BIOLOGICAL

Given by IV infusion

Also known as: Autologous TIL LN-144, Autologous Tumor Infiltrating Lymphocytes LN-144, Contego, LN-144

Treatment (pembrolizumab, lifileucel)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, lifileucel)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Treatment (pembrolizumab, lifileucel)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must be 18 to 75 years of age
• Must have a confirmed diagnosis of Stage IIIB-D locally advanced or Stage IV melanoma (American Joint Committee on Cancer \[AJCC\] 8th edition) with measurable disease in the lymph node(s) documented by computed tomography (CT) or ultrasound imaging (\>= 15 mm short axis) or by physical exam. Patients must also have measurable primary site of disease, including cutaneous and/or intransit metastases by imRECIST (\>= 20 mm chest x-ray \[CXR\], \>= 10 mm CT, or \>= 10 mm by exam)
• No prior therapy is allowed
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and an estimated life expectancy of \>= 3 months in the opinion of the investigator
• Patients must have at least one easily accessible measurable tumor-involved lymph node(s) documented by CT or ultrasound imaging for TIL harvest
• Patients must be amenable to have ultrasound examination of measurable lymph node(s) and have pathologic confirmation of melanoma metastases in the lymph node (fine needle aspiration \[FNA\] acceptable) in the 28 days preceding the first administration of the treatment
• Patients with and without BRAF V600E/K mutations are included.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
• Patients with a history of herpes simplex virus (HSV) infection must have been treated. Patients with a history of Epstein-Barr virus (EBV) or cytomegalovirus (CMV) infection must be asymptomatic and have low viral loads
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional classification. To be eligible for this trial, patients should be class 2B or better
• Women must not be pregnant or breast-feeding due to potential harm to an unborn fetus and possible risk of adverse events in nursing infants with the anti-PD-1 regimen(s) being used.
• All females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
• A female of childbearing potential is defined as any woman, regardless of sexual orientation, or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding consecutive months)

You may not qualify if:

• Ocular/uveal melanoma
• Chemotherapy or radiotherapy within 4 weeks before baseline (6 weeks for nitroso-urea and mitomycin C)
• Contraindication for the use of vasopressor agents
• Patients with HIV active infection or seropositivity are excluded. Patients with active Hep B or Hep C based on serology and viral load are excluded. Patients with active CMV or EBV based on serology and viral load are excluded.
• History or current manifestation of severe progressive heart disease (congestive heart failure with LVEF \< 50% by echocardiogram or MUGA scan, coronary artery disease, uncontrolled arterial hypertension, uncontrolled arrhythmia, or myocardial infarction in the past 6 months.
• Patients with active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids.
• Patients should be excluded if they had prior treatment with an anti- PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways.
• Patients who have a history of hypersensitivity to immune checkpoint therapy drug(s) or any component or excipient of LN-144 or other study drugs:
• Nivolumab, pembrolizumab, or related products
• Any monoclonal antibody
• NMA-LD preconditioning regimen (cyclophosphamide, mesna, and fludarabine)
• Proleukin, aldesleukin, IL-2
• Antibiotics (ABX) of the aminoglycoside group (i.e., streptomycin, gentamicin); except those who are skin-test negative for gentamicin hypersensitivity
• Any component of the LN-144 infusion product formulation including dimethyl sulfoxide (DMSO), human serum albumin (HSA), IL-2, and dextran-40
• History of chronic autoimmune disease (Addison's disease, multiple sclerosis, Graves' disease, rheumatoid arthritis, systemic lupus erythematosus, etc…) except patient with active vitiligo or a history of vitiligo. Patients with history of psoriasis is allowed

Sponsors & Collaborators

• Richard Wu: lead
• Iovance Biotherapeutics, Inc.: collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Melanoma

Interventions

Cyclophosphamide; fludarabine; lifileucel; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; 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

Study Officials

• Richard C Wu, M.D. Ph.D.

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 17, 2021
• First Posted: January 4, 2022
• Study Start: July 1, 2022
• Primary Completion: July 14, 2023
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)