Efficacy & Safety for LN144 With Pembrolizumab With High Risk Stage IIIb-dResectable Melanoma

NCT06190249 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: CASE4622
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the efficacy of adjuvant adoptive cell therapy (ACT) via infusion of LN-144 (autologous TIL) followed by interleukin-2 (IL-2) after a nonmyeloablative lymphodepletion (NMA-LD) preparative regimen, followed by Pembrolizumab.

Conditions

Stage IIIB Melanoma; Stage IIIC Melanoma; Stage IIID Melanoma

Keywords

Autologous Tumor Infiltrating Lymphocytes; LN144; Resectable Melanoma; Immunotherapy Naive

Outcome Measures

Primary Outcomes (2)

• LN-144 Efficacy

  measured as the rate of RFS (Relapse-Free Survival)

  1 year following TIL infusion

• LN-144 Safety Profile

  measured by the incidence Serous Adverse Events (SAE)

  Within 30 days of LN-144 administration

Secondary Outcomes (6)

• LN-144+ Pembrolizumab Efficacy Overall Survival (OS)

  1 year after initial treatment

• LN-144+ Pembrolizumab Efficacy Relapse-Free Survival (RFS)

  1 year after initial treatment

• LN-144+ Pembrolizumab Efficacy Distant Metastasis-Free Survival (DMFS)

  1 year after inital treatment

• LN-144 Safety Profile

  within 12 months of LN144 administration

• Location of relapse

  Up to 3 years

Study Arms (1)

LN-144 Therapy

EXPERIMENTAL

All patients will receive LN-144 therapy, consisting of these steps: 1. Harvest (surgical resection of tumor tissue) to provide the autologous tissue that serves as the source of LN-144. 2. Production of LN-144 investigational product (IP) at a central Good Manufacturing Practice (GMP) facility 3. A 5-day nonmyeloablative lymphodepletion (NMA-LD) preparative regimen 4. Infusion of the LN-144 product (Day 0) 5. Administration of IV interleukin-2 (IL-2) for ≤ 6 doses. 6. Infusion of pembrolizumab 200 mg (Week 12) every 3 weeks for up to 1 year (17 cycles)

Biological: LN-144; Drug: Cyclophosphamide; Drug: Mesna; Drug: Fludarabine; Biological: Interleukin-2 (IL-2); Drug: Pembrolizumab

Interventions

LN-144 BIOLOGICAL

A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepleting chemotherapy including cyclophosphamide and fludarabine, patient is infused with autologous TIL (LN-144), followed by IL-2.

Also known as: Autologous Tumor Infiltrating Lymphocytes (TIL)

LN-144 Therapy

Cyclophosphamide DRUG

Given by IV.

Also known as: Cytoxan

LN-144 Therapy

Mesna DRUG

Given by IV.

Also known as: Mesnex

LN-144 Therapy

Fludarabine DRUG

Given by IV.

Also known as: Fludara

LN-144 Therapy

Interleukin-2 (IL-2) BIOLOGICAL

Given by IV.

Also known as: Aldesleukin, Proleukin

LN-144 Therapy

Pembrolizumab DRUG

Given by IV.

Also known as: Keytruda

LN-144 Therapy

Eligibility Criteria

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

You may qualify if:

• Must have a confirmed diagnosis of resectable, Stage III, High-Risk melanoma defined by AJCC v8 as Stage IIIB, IIIC, or IIID.
• Disease must be resected to no evidence of disease on imaging and no gross disease residually with the exception of positive microscopic margin. No prior treatment with immunotherapy.
• One (1) lesion at least 1.5cm in size (solitary or aggregate) available for TIL harvesting that has not undergone prior embolization or RT in prior 3 months unless subsequent growth is demonstrated.
• Palliative radiation therapy is permitted so long as it does not involve lesions being selected for TIL. Washout is not required if all related toxicities have resolved to ≤ Grade 1 as per CTCAE v 5.0
• Previous surgical procedure(s) is/are permitted provided that wound healing has occurred, all complications have resolved, and at least 14 days have elapsed (for major operative procedures) prior to the tumor resection.
• Patients must have a washout period ≥ 21 days from prior anti-cancer therapy(ies) to the start of the planned NMA-LD pre-conditioning regimen.
• Patients must be ≥ 18 years of age at the time of consent.
• 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 the following hematologic parameters:• Absolute neutrophil count (ANC) ≥ 1000/mm3, •Hemoglobin (Hb) ≥ 9.0 g/dL, •Platelet ≥ 100,000/mm3
• Patients must have adequate organ function: •Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal (≤ 3 × ULN); patients with liver metastasis ≤ 5 × ULN, •Estimated creatinine clearance (eCrCl) ≥ 40 mL/min using the Cockcroft-Gault formula at Screening, •Total bilirubin ≤ 2 mg/dL, •Patients with Gilbert's syndrome must have a total bilirubin ≤ 3 mg/dL
• Patients of childbearing potential (or female partners of male participants) must be willing to take the appropriate precaution to avoid pregnancy or fathering a child for the duration of the study and practice an approved, highly effective method of birth control during treatment and for 12 months after their last dose of IL-2.
• Approved methods of birth control are as follows: 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, Vasectomized partner, True sexual abstinence when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar ovulation, symptothermal, post-ovulation methods) is not acceptable
• Patients (or legally authorized representative) must have the ability to understand the requirements of the study, have provided written informed consent as evidenced by signature on an ICF approved by an Institutional Review Board/Independent Ethics Committee (IRB/IEC), and agree to abide by the study restrictions and return to the site for the required assessments, including the OS Follow-up Period.

You may not qualify if:

• Patients who have received an organ allograft or prior cell transfer therapy within the past 20 years that included a non-myeloablative or myeloablative chemotherapy regimen.
• Patients with melanoma of uveal/ocular origin.
• Patients who have a history of hypersensitivity to any component or excipient of LN-144 or other study drugs:
• NMA-LD preparative regimen (cyclophosphamide, mesna, and fludarabine),
• Proleukin®, aldesleukin, IL-2,
• Pembrolizumab,
• 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.
• Patients with symptomatic and/or untreated brain metastases (of any size and any number).
• Patients who are on chronic systemic steroid therapy except for those requiring steroid therapy for management of adrenal insufficiency; these patients may receive no more than 10 mg of prednisone or its equivalent daily.
• Patients who are pregnant or breastfeeding.
• Patients who have active medical illness(es) that would pose increased risk for study participation, including: active systemic infections requiring systemic ABX, coagulation disorders, or other active major medical illnesses of the cardiovascular, respiratory, or immune systems.
• Patients must have a negative syphilis assay (per local standard, e.g., rapid plasma reagin \[RPR\], venereal disease research laboratory \[VDRL\]) and be seronegative for the human immunodeficiency virus (HIV1 and HIV2 antibody titers). Patients with positive serology for hepatitis B virus surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) or hepatitis C virus (anti-HCV) indicating acute or chronic infection must have the corresponding polymerase chain reaction (PCR) assay; patients may be enrolled if the viral load by PCR is undetectable with/without active treatment. Additional serology testing may be required depending on local prevalence of certain viral exposures
• Patients who have any form of primary immunodeficiency (e.g., severe combined immunodeficiency disease \[SCID\] and acquired immunodeficiency syndrome \[AIDS\])
• Patients who have received a live or attenuated vaccination within 28 days prior to the start of NMA-LD pre-conditioning regimen.

Sponsors & Collaborators

• James Isaacs, MD: lead
• Iovance Biotherapeutics, Inc.: collaborator

MeSH Terms

Conditions

Melanoma

Interventions

lifileucel; Cyclophosphamide; Mesna; fludarabine; fludarabine phosphate; Interleukin-2; aldesleukin; 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; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• James Isaacs, MD

  Cleveland Clinic Taussig Cancer Institute, Case 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: MD

Study Record Dates

• First Submitted: December 14, 2023
• First Posted: January 5, 2024
• Study Start: December 2, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: June 5, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share