Melanoma (Skin Cancer), Unresectable Melanoma, Metastatic Melanoma
Conditions
Keywords
Tumor Infiltrating Lymphocytes, TIL, Metastatic Melanoma, Unresectable Melanoma, Cell Therapy, Cellular Immuno-therapy, IL-2, Non-myeloablative lymphodepletion (NMALD), Melanoma, Lifileucel, Skin Cancer, LN-144, BRAF v600, BRAF/MEK
Brief summary
This is a Phase 2, multicenter, open-label study of lifileucel (tumor-infiltrating lymphocytes \[TIL\]) in participants with previously treated advanced melanoma
Detailed description
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 and/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
Interventions
BIOLOGICALLifileucel
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.
Sponsors
Iovance Biotherapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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 and/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. * 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | 5 years | To evaluate the efficacy of lifileucel as measured by ORR per RECIST v1.1 as assessed by the IRC |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | 5 years | To evaluate the efficacy of lifileucel as measured by DOR per RECIST v1.1 as assessed by the IRC |
| Disease Control Rate | 5 years | To evaluate the efficacy of lifileucel as measured by DCR per RECIST v1.1 as assessed by the IRC |
| Progression-Free Survival | 5 years | To evaluate the efficacy of lifileucel as measured by PFS per RECIST v1.1 as assessed by the IRC |
| Complete Response Rate | 5 years | To evaluate the efficacy of lifileucel as measured by CR rate per RECIST v1.1 as assessed by the IRC |
| Overall Survival | 5 years | To evaluate the efficacy of lifileucel as measured by OS |
| Adverse Events | 5 years | To demonstrate safety and tolerability of lifileucel |
| Objective Response Rate | 5 years | To evaluate the efficacy of lifileucel as measured by ORR per RECIST v1.1 as assessed by the investigators |
Countries
Australia, Canada, United Kingdom, United States
Contacts
Primary ContactIovance Biotherapeutics Study Team
Outcome results
None listed