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Also known as Lifileucel Manufacturing Clinical v Research, Lifileucel Infusion, LN-145, LN-144, Tumor-Infiltrating Lymphocytes, TIL, Autologous TIL LN-144, Autologous Tumor Infiltrating Lymphocytes LN-144
Lifileucel · 10 trials · 22 indications
To compare the efficacy of lifileucel plus pembrolizumab with the efficacy of pembrolizumab alone measured by objective response rate (ORR) and progression-free survival (PFS) assessed by the blinded independent review committee (BIRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
To evaluate the efficacy of lifileucel as measured by ORR per RECIST v1.1 as assessed by the IRC
Tumor-infiltrating lymphocyte (TIL) production is defined by the successful tumor harvest that leads to a manufacturing of a TIL product that contains ≥ 1 x 10\^9 cells.
TIL administration is defined by the administration of NMA-LD, complete infusion of TIL therapy and at least 1 dose of interleukin-2 (IL-2).
TEAEs will determined on the Common Toxicity Criteria for Adverse Events Version 5.0 (CTCAEv5) as reported on case report forms.
Evaluate the efficacy of LN-144 in patients with unresectable or metastatic melanoma using the objective response rate (ORR), as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for Cohorts 1 \& 3 and as assessed by Independent Review Committee (IRC) per RECIST Version 1.1 for Cohorts 2 \& 4
Success rate of tumor infiltrating lymphocyte (TIL) expansion from all screened eligible patients who have had tumor-involved lymph node(s) removed; percentage of all eligible patients who have completed the screening and treated with LN-144/lifileucel.
The severity of AEs will be graded according to CTCAE version 5.0, and frequencies and percentages of patients with AEs will be tabulated by severity grade.
Number of viable TILs (cell count) harvested from resected tumor tissue.
| Arm | Type | Description |
|---|---|---|
| Arm A | EXPERIMENTAL | Lifileucel plus Pembrolizumab |
| Arm B | ACTIVE_COMPARATOR | Pembrolizumab alone with Optional Crossover Period |
| Lifileucel | EXPERIMENTAL | - |
| Cohort A: CSCC Autologous TIL Therapy | EXPERIMENTAL | 10 participants with CSCC will complete: * Screening visit * Surgical procedure to collect tissue, called TIL harvest * Baseline visit * Days -5 through -1: Predetermined dose of Lymphodepleting Chemotherapy, Fludarabine, 1x daily * Days -5 and -4: Predetermined dose of Lymphodepleting Chemotherapy, Cyclophosphamide, 1x daily * Day 0: TIL infusion * Days 0, 1, 2, 3, 4, and 14: Predetermined dose of IL-2 1x daily for up to 6 doses * Imaging at weeks 6 and 12 * End of treatment visit with imaging * Long term follow up every 3 months for up to 3 years |
| Cohort B: MCC Autologous TIL Therapy | EXPERIMENTAL | 4 participants with MCC will complete: * Screening visit * Surgical procedure to collect tissue, called TIL harvest * Baseline visit * Days -5 through -1: Predetermined dose of Lymphodepleting Chemotherapy, Fludarabine, 1x daily * Days -5 and -4: Predetermined dose of Lymphodepleting Chemotherapy, Cyclophosphamide, 1x daily * Day 0: TILs infusion * Days 0, 1, 2, 3, 4, and 14: Predetermined dose of IL-2 1x daily for up to 6 doses * Imaging at weeks 6 and 12 * End of treatment visit with imaging * Long term follow up every 3 months for up to 3 years |
| Single Arm | EXPERIMENTAL | Lifileucel |
| Patients with Endometrial Cancer | EXPERIMENTAL | - |
| Cohort 1 | EXPERIMENTAL | Patients whose tumors did not express programmed cell death-ligand 1 (PD-L1), i.e., tumor proportion score (TPS) \< 1% prior to ICI treatment and Patients with no available historical TPS for PD-L1 expression |
| Cohort 2 | EXPERIMENTAL | Patients whose tumors expressed PD-L1 TPS ≥1% prior to ICI treatment |
| Cohort 3 | EXPERIMENTAL | Patients, regardless of tumor PD-L1 TPS prior to ICI treatment, who are unable to safely undergo a surgical tumor resection for TIL generation |
| Cohort 4 | EXPERIMENTAL | Patients, regardless of tumor PD-L1 expression status prior to ICI treatment, who have meet all inclusion/exclusion criteria except the requirement to have documented disease progression may elect to have the tumor harvest procedure and TIL production prior to disease progression on their current anticancer treatment. Documentation of progressive disease and identification of a target lesion for RECIST v1.1 assessment is required at Baseline for these patients. |
| Retreatment Cohort | EXPERIMENTAL | Patients who were previously treated with LN-145 in Cohort 1, 2, 3, or 4. |
| Cohort 5 | EXPERIMENTAL | LN-145 cryopreserved/LN-145-S1 cryopreserved TIL re-treatment |
| Treatment (pembrolizumab, lifileucel) | EXPERIMENTAL | Patients receive pembrolizumab IV on day -14, cyclophosphamide IV QD on days -7 to -6, fludarabine IV over 30 minutes QD on days -5 to -1, and lifileucel IV infusion on day 0. Patients also receive pembrolizumab IV on day 28 and 70, and undergo surgery on day 80. MAINTENANCE: Patients receive pembrolizumab IV every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. |
| CD8 PET/CT imaging for lifileucel therapy | EXPERIMENTAL | CD8 PET/CT imaging prior to tumor resection (PET0) and after lifileucel treatment. |
| Name | Type | Description |
|---|---|---|
| Lifileucel plus Pembrolizumab | BIOLOGICAL | A tumor sample is resected from each patient for Lifileucel manufacturing. Patients then receive Pembrolizumab followed by the lifileucel regimen which consists of non-myeloablative lymphodepletion, lifileucel infusion followed by IL-2. Patients will then continue to receive Pembrolizumab every 6 weeks until disease progression. |
| Pembrolizumab with Optional Crossover Period | BIOLOGICAL | Patient will receive Pembrolizumab monotherapy every 6 weeks until disease progression. Upon verified confirmed disease progression by the blinded independent review central committee, patients may proceed to lifileucel monotherapy during an optional crossover period if they meet eligibility criteria. Optional crossover: A tumor sample is resected from each patient for Lifileucel manufacturing. Patients then receive the lifileucel regimen which consists of non-myeloablative lymphodepletion, lifileucel infusion followed by IL-2. |
| Lifileucel | BIOLOGICAL | Study intervention will begin with a tumor resection from which lifileucel will be generated. The lifileucel regimen consists of a preparative NMA-LD regimen (ie, cyclophosphamide with mesna followed by fludarabine), the lifileucel infusion, and an abbreviated course of aldesleukin (interleukin-2). |
| LN-145 | BIOLOGICAL | Autologous tumor-infiltrating lymphocytes via intravenous (into the vein) infusion per protocol |
| Cyclophosphamide | DRUG | Antineoplastic drug, multi-dose vial, per institutional standards |
| Fludarabine | DRUG | Nucleotide metabolic inhibitor, single-use vial, via intravenous infusion per institutional standards |
| Interleukin-2 | BIOLOGICAL | Recombinant, human glycoprotein, single-use vial, via intravenous infusion per protocol |
| LN-145-S1 | BIOLOGICAL | A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After NMA lymphodepletion, patients are infused with autologous TIL (LN-145-S1) followed by IL-2 administration. |
| Pembrolizumab | BIOLOGICAL | Given IV |
| Therapeutic Conventional Surgery | PROCEDURE | Undergo surgery |
| Resection of PET (high) and PET (low) Tumors | PROCEDURE | Harvest of two tumors to obtain tissue for manufacturing the autologous tumor-infiltrating lymphocyte (TIL) cellular product. |
| Lifileucel Manufacturing Clinical v Research | BIOLOGICAL | Production of lifileucel (AMTAGVI) for participant infusion) and comparator lifileucel (AMTAGVI) at a centralized Good Manufacturing Practice (GMP)-compliant facility. |
| Chemotherapy Regimen | DRUG | Administration of a 7-day lymphodepleting (LD) chemotherapy regimen prior to lifileucel infusion. |
| Lifileucel Infusion | BIOLOGICAL | Administration of CD8 PET-guided infusion of lifileucel (AMTAGVI) on Day 0 following completion of the lymphodepleting chemotherapy regimen. |
| IL-2 | DRUG | Administration of up to six doses of intravenous interleukin-2 (IL-2) following lifileucel (AMTAGVI) infusion. |
| CD8 PET | PROCEDURE | CD8 PET/CT imaging will be performed before tumor resection and after lifileucel (AMTAGVI) administration (PET1). |
Inclusion Criteria: 1. Participant has a histologically or pathologically confirmed diagnosis of Stage IIIC, IIID, or IV unresectable or metastatic melanoma. 2. In the investigator's assessment, the participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and an est...
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Lifileucel is an investigational cell therapy being developed by Iovance Biotherapeutics, Inc. (IOVA) for advanced solid tumors. It is a tumor-infiltrating lymphocyte (TIL) therapy, meaning it uses immune cells taken from a patient's own tumor. It is being studied in melanoma, endometrial cancer, and soft tissue sarcoma.
Lifileucel is being studied for the treatment of several advanced cancers, including unresectable or metastatic melanoma, endometrial cancer, and soft tissue sarcoma such as undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. It is an investigational therapy and has not been approved for any indication.
Lifileucel is being developed by Iovance Biotherapeutics, Inc., which trades on the Nasdaq under the ticker IOVA. The company is running clinical trials of lifileucel in melanoma, endometrial cancer, and soft tissue sarcoma.
Lifileucel is in Phase 2 clinical development. It is an investigational cell therapy and is not FDA approved. The clinical program includes Phase 2 trials in advanced melanoma, endometrial cancer, and soft tissue sarcoma, as well as an early Phase 1 imaging study in melanoma.
Lifileucel is being evaluated in several clinical trials, including NCT07741877 in advanced soft tissue sarcoma, NCT07700121 in unresectable or metastatic melanoma, NCT07288203 in advanced melanoma, and NCT06481592 in advanced endometrial cancer. These trials are recruiting or ongoing in the United States and other countries.