A Study of Lifileucel (Tumor-infiltrating Lymphocytes) in Adults With Advanced Melanoma

This is a Phase 2 study of the lifileucel treatment regimen in participants who previously received treatment for unresectable or metastatic (advanced) melanoma with 1 prior line of an anti-programmed cell death protein-1 (PD-1) or anti-programmed death ligand 1 (PD-L1) agent or whose melanoma progressed during or within ≤ 12 weeks after adjuvant anti-PD-(L)1 treatment (early relapse). Participants who have BRAF V600 mutation positive melanoma may have received or refused 1 additional prior line treatment with a BRAF inhibitor

± a MEK inhibitor

• Lifileucel (Biological), also known as LN-144: A tumor sample is resected from each patient for lifileucel manufacturing. Patients will first receive the preparative non-myeloablative lymphodepletion (NMA-LD) regimen. They will then receive the lifileucel infusion, followed by an abbreviated course of aldesleukin.

Primary outcomes

• Objective Response Rate [12 months]: To evaluate the efficacy of lifileucel as measured by ORR per RECIST v1.1 as assessed by the investigators

Secondary outcomes

• Complete Response Rate [12 months]: To evaluate the efficacy of lifileucel as measured by CR rate per RECIST v1.1 as assessed by the investigators
• Duration of Response [12 months]: To evaluate the efficacy of lifileucel as measured by DOR per RECIST v1.1 as assessed by the investigators
• Disease Control Rate [12 months]: To evaluate the efficacy of lifileucel as measured by DCR per RECIST v1.1 as assessed by the investigators
• Progression-Free Survival [12 months]: To evaluate the efficacy of lifileucel as measured by PFS per RECIST v1.1 as assessed by the investigators
• Overall Survival [18 months]: To evaluate the efficacy of lifileucel as measured by OS
• Adverse Events [18 months]: To demonstrate safety and tolerability of lifileucel

Sex: All, ages: 18 Years to 70 Years

Inclusion Criteria:

* Participant has a histologically or pathologically confirmed diagnosis of Stage IIIC, IIID, or IV unresectable or metastatic melanoma.
* The participant has an ECOG performance status of 0 or 1 and an estimated life expectancy of > 6 months.
* The participant must have experienced radiographic disease progression on: 1 prior line of an anti-PD-(L)1 treatment (as a monotherapy or as part of a combination) for advanced melanoma or during or within ≤ 12 weeks after adjuvant anti-PD-(L)1 treatment (as a monotherapy or as part of a combination). Participants who have BRAF V600 mutation positive melanoma may have received 1 additional prior line of treatment with a BRAF inhibitor ± a MEK inhibitor or choose lifileucel as an alternative option to a BRAF inhibitor ± a MEK inhibitor.
* Participant is assessed as having at least one resectable lesion (or aggregate lesions) for lifileucel generation.
* Participant must have at least one measurable disease as defined by RECIST 1.1 following tumor resection.
* Participants who are > 70 years of age may be allowed to enroll after the investigator discusses with the medical monitor.
* Participants of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of highly effective birth control.
* Participants must have adequate organ function.
* Participant is willing to receive optimal supportive care, including intensive care, from enrollment until the first post-treatment tumor assessment.

Exclusion Criteria:

* Participant has melanoma of uveal/ocular origin.
* Participant has symptomatic untreated brain metastases.
* Participant has active uveitis that requires active treatment.
* Participant has an active medical illness(es) that, in the opinion of the investigator, would pose increased risks for study participation, such as systemic infections; seizure disorders; coagulation disorders; or other active major medical illnesses of the cardiovascular, respiratory, or immune systems.
* Participant has any form of primary or acquired immunodeficiency (eg, SCID or AIDS).
* Participant had another primary malignancy within the previous 3 years (except for those that do not require treatment or were curatively treated >1 year ago, and in the judgment of the investigator do not pose a significant risk of recurrence.)
* Participant has a history of allogeneic cell or organ transplant.
* Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.

Other protocol defined inclusion/exclusion criteria could apply.

NIH grants: 2025