Lifileucel and Pembrolizumab for the Treatment of Locally Advanced Stage IIIB-D Melanoma

• Status: Not yet recruiting
• Trial end date: 2025-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This phase I/II trial tests the safety and side effects of lifileucel and pembrolizumab in treating patients with stage IIIB-D melanoma that has spread to nearby tissue or lymph nodes (locally advanced). Biological therapies, such as 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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Richard Wu
• Collaborator: Iovance Biotherapeutics, Inc.
• Treatments: Cyclophosphamide; Fludarabine; Pembrolizumab

Criteria

Inclusion Criteria:

• Patient must be 18 to 75 years of age

• Must have a confirmed diagnosis of Stage IIIB-D locally advanced 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

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Patients with detectable viral loads are excluded due to the potential myelosuppression with the chemotherapy conditioning regimen

• Patients with a history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection must have been treated and cured. For patients with HBV/HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

• 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)

• Women of childbearing potential and sexually active males must not conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of study registration and continuing until at least 5 months after the last dose of anti-PD-1 treatment for female patients and for at least 7 months after the last dose of anti-PD-1 treatment for male patients who are sexually active with a woman of childbearing potential (WOCBP)

• Hemoglobin >= 10 g/dL (=< 4 weeks prior to protocol registration)

• Neutrophils >= 1500/ul (=< 4 weeks prior to protocol registration)

• Leukocytes >= 3000/ul (=< 4 weeks prior to protocol registration)

• Lymphocytes >= 700/ul (=< 4 weeks prior to protocol registration)

• Blood platelet >= 100,000/ul (=< 4 weeks prior to protocol registration)

• Serum creatinine =< 1.5 x upper limit of normal or creatinine clearance (CrCl) >= 40 mL/min (if using the Cockcroft-Gault formula) (=< 4 weeks prior to protocol registration)

• Serum bilirubin =< 2.0 mg/dL (=< 4 weeks prior to protocol registration)

• Total bilirubin =< 1.5 x upper limit of normal (except for patients with Gilbert syndrome, who can have total bilirubin < 3 mg/dL) (=< 4 weeks prior to protocol registration)

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2 x upper limit of normal (=< 4 weeks prior to protocol registration)

• Lactate dehydrogenase (LDH) =< 1.5 x upper limit of normal (=< 4 weeks prior to protocol registration)

• 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 informed consent form (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 RFS follow-up period

Exclusion Criteria:

• Ocular/uveal melanoma

• Contraindication for the use of vasopressor agents

• History or current manifestation of severe progressive heart disease (congestive heart failure, coronary artery disease, uncontrolled arterial hypertension, uncontrolled arrhythmia, or myocardial infarction) in the past 6 months

• 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

• History of inflammatory bowel disease, celiac disease, or other chronic gastrointestinal conditions associated with diarrhea

• Patients who have had another primary malignancy within the previous 3 years (except for those which do not require treatment or have been curatively treated > 1 year ago, and in the judgment of the Investigator, does not pose a significant risk of recurrence including, but not limited to, non-melanoma skin cancer, ductal carcinoma in situ [DCIS], lobular carcinoma in situ [LCIS], prostate cancer Gleason score =< 6). Unchecked thyroid dysfunction

• Any serious, acute or chronic illness (i.e., active infection) needing antibiotics administration, coagulation's disorders, or any medical disorder requiring unauthorized concomitant treatment described in this study

• Positive viral serology for HIV (human immunodeficiency virus) 1/2, p24 Ag, human T-lymphotropic virus (HTLV)1, HTLV2, B and C hepatitis or syphilis

• Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days before study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intraarticular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if > 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted

• Patients who have obstructive or restrictive pulmonary disease and have a documented forced expiratory volume in 1 second (FEV1) of =< 60% of predicted normal:

• If a patient is not able 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 who are unable to walk a distance of at least 80% predicted for age and sex or demonstrates evidence of hypoxia at any point during the test (SpO2 < 90%) are excluded

• Active infections, including coronavirus disease 2019 (COVID-19), within 30 days

• Participated in another clinical study with an investigational product within 21 days of the initiation of treatment

• Adults under a legal protection regime (i.e., guardianship, trusteeship)