Reduced Dose Fludarabine/Cyclophosphamide Lymphodepletion Before Tumor-Infiltrating Lymphocyte Therapy With Lifileucel in Metastatic Melanoma
This phase II trial tests how well lifileucel, with reduce dose fludarabine and cyclophosphamide for lymphodepletion and interleukin-2, work for treating patients with melanoma that cannot be removed by surgery (unresectable) or that has spread from where it first started (primary site) to other places in the body (metastatic).Lifileucel is made up of specialized immune cells called lymphocytes or T cells that are taken from a patient's tumor, grown in a manufacturing facility and infused back into the preconditioned patient to attack the tumor. Giving Lifileucel with a reduced dose of fludarabine and cyclophosphamide for lymphodepletion and interleukin -2 is being studied in patients with unresectable or metastatic melanoma.
• Males and females age ≥ 18 years Enrollment of patients ≥ 70 years of age may be allowed at principal investigator discretion.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
• At least one measurable target lesion, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
‣ Lesions in previously irradiated areas (or other local therapy) should not be selected as target lesions, unless treatment was ≥ 3 months prior to Screening, and there has been demonstrated disease progression in that lesion
• Women of childbearing potential must have a negative serum pregnancy test 48 hours prior to initiating treatment
• Patients with unresectable or metastatic melanoma (stage IIIc or stage IV)
• Patients must have progressed following 1-3 prior systemic therapy including a programmed cell death protein-1 (PD-1) blocking antibody; and if proto-oncogene B-Raf (BRAF) V600 mutation positive, a BRAF inhibitor or BRAF inhibitor in combination mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor
• At least one resectable lesion (or aggregate of lesions resected) of a minimum 1.5 cm in diameter post-resection to generate TIL; surgical removal with minimal morbidity (defined as any procedure for which expected hospitalization is ≤ 3 days)
• Adequate hematologic and organ function
• Patients must have recovered from all prior therapy-related adverse events (AEs) to ≤ grade 1 (per Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 5.0), except for alopecia or vitiligo, prior to enrollment (tumor resection)
‣ Patients with documented ≥ grade 2 diarrhea or colitis because of previous treatment with immune checkpoint inhibitor(s) must have been asymptomatic for at least 6 months and/or had a normal colonoscopy post-immune checkpoint inhibitor treatment, by visual assessment, prior to tumor resection
• Patients with immunotherapy-related endocrinopathies stable for at least 6 weeks (eg, hypothyroidism), and controlled with hormonal replacement (non-corticosteroids), are allowed
• Patients must have a washout period of ≥ 28 days from prior anticancer therapy(ies) to the start of the planned reduced dose lymphodepletion (RDL) preconditioning regimen:
‣ Targeted therapy: MEK/BRAF or other targeted agents
⁃ Chemotherapy
⁃ Immunotherapy: anti-CTLA-4/anti-PD-1, other monoclonal antibodies (mAb), or vaccine
⁃ Palliative radiation therapy is permitted so long as it does not involve lesions being selected for TIL, or as target or non-target lesions. Washout is not required if all related toxicities have resolved to ≤ grade 1 as per CTCAE v 5.0
• Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence or to use the forms of contraception listed in Child-Bearing Potential/Pregnancy section for the duration of study participation and for 12 months following the last dose of IL-2 or until the first dose of the next anti-cancer therapy, whichever occurs first