Investigational Drug
LN-145
HealthScout AI Analysis
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Overview
- LN-145 (lifileucel; brand name Amtagvi) is an autologous tumor-infiltrating lymphocyte (TIL) therapy manufactured from a patient’s own resected tumor, expanded ex vivo, and reinfused after non‑myeloablative lymphodepletion and followed by high‑dose IL‑2 support. On February 16, 2024, lifileucel received U.S. FDA accelerated approval for adults with unresectable or metastatic melanoma previously treated with anti–PD‑1 therapy and, if BRAF V600–mutant, targeted therapy. Approval was based on objective response rate and durability of response. Continued approval may be contingent on confirmatory trials. (fda.gov)
Mechanism of action
- The specific mechanism of action of lifileucel is not fully defined; as a TIL product, it contains a heterogeneous mixture of tumor‑reactive T cells (primarily CD4+ and CD8+) expanded from the patient’s tumor and is intended to mediate anti‑tumor activity upon reinfusion. (fda.gov)
Efficacy
Melanoma (post–checkpoint inhibitor setting) - Pivotal single‑arm, multicenter study (C‑144‑01; cohorts within the recommended dose range): ORR 31.5% (95% CI 21.1–43.4); median time to response 1.5 months; median duration of response (DoR) not reached at data cutoff. (fda.gov) - Pooled analysis of consecutive cohorts (C‑144‑01 cohorts 2 and 4; n=153) by independent review committee: ORR 31.4% with complete responses in ~6%; median DoR not reached at analysis; median overall survival ~13.9 months in the heavily pretreated population. Longer‑term updates report durable responses with a substantial proportion ongoing beyond 18 months. (pmc.ncbi.nlm.nih.gov)
Non–small cell lung cancer (NSCLC; investigational) - Phase 2 multicenter study in metastatic NSCLC resistant to immune checkpoint inhibitors (n=28): ORR 21.4% (6/28) with responses observed even in PD‑L1–negative, low TMB, and STK11‑mutant tumors; two treatment‑emergent deaths were reported. (aacrjournals.org)
Cervical cancer (investigational) - Phase 2 C‑145‑04 (ASCO 2019): in 27 evaluable patients with recurrent/metastatic or persistent cervical cancer after prior therapy, ORR 44% (3 CR, 9 PR); median DoR not reached at 7.4‑month median follow‑up. Study uses the same lymphodepletion/IL‑2‑supported LN‑145 approach. (ascopubs.org)
Ongoing/confirmatory studies - A randomized phase 3 trial (TILVANCE‑301) is evaluating lifileucel plus pembrolizumab versus pembrolizumab alone in previously untreated advanced melanoma. (ascopubs.org)
Safety
- Boxed Warning: treatment‑related mortality; prolonged severe cytopenias; severe infection; cardiopulmonary and renal impairment. Administration must occur in an inpatient setting with intensive care capability. (fda.gov)
- Common adverse reactions (≥20%): chills, fever, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash, hypotension, alopecia, infection, hypoxia, and dyspnea. Grade ≥3 cytopenias are frequent (e.g., thrombocytopenia 78%, neutropenia 69%, anemia 58%). Serious adverse reactions leading to death have included severe infections, internal organ hemorrhage, acute renal/respiratory failure, and arrhythmia. The overall safety profile largely reflects effects of the lymphodepleting chemotherapy and high‑dose IL‑2. (fda.gov)
- In the NSCLC phase 2 study, adverse events were consistent with expectations for TIL therapy; two treatment‑emergent deaths (cardiac failure and multiorgan failure) were reported. (aacrjournals.org)
Further reading
- FDA accelerated approval notice for lifileucel (melanoma): https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lifileucel-unresectable-or-metastatic-melanoma (fda.gov)
- Amtagvi (lifileucel) Prescribing Information (Feb 2024 PDF): https://www.fda.gov/media/176417/download (fda.gov)
- Pooled analysis in post‑ICI melanoma (C‑144‑01; J Immunother Cancer 2022): https://pmc.ncbi.nlm.nih.gov/articles/PMC9748991/ (pmc.ncbi.nlm.nih.gov)
- Phase 2 melanoma study (J Clin Oncol 2021): https://pubmed.ncbi.nlm.nih.gov/33979178/ (pubmed.ncbi.nlm.nih.gov)
- NSCLC phase 2 study (Cancer Discovery 2024): https://aacrjournals.org/cancerdiscovery/article/14/8/1389/746508/Lifileucel-an-Autologous-Tumor-Infiltrating (aacrjournals.org)
- Cervical cancer phase 2 (ASCO 2019 abstract): https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.2538 (ascopubs.org)
- Phase 3 TILVANCE‑301 design (ASCO 2023 abstract): https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.TPS9607 (ascopubs.org)
Note: As of October 7, 2025, lifileucel is FDA‑approved for melanoma as above; use in other tumor types remains investigational pending results of ongoing trials. (fda.gov)
Last updated: Oct 2025
Active trials using LN-145
Found 7 active trials using this drug:
HealthScout AI summary: Adults with unresectable or metastatic cutaneous (including acral) melanoma who are HLA‑A*02:01 positive and have progressed after PD‑1 therapy (and BRAF‑directed therapy if mutated) are randomized to autologous PRAME‑targeted TCR‑T cells (IMA203) after lymphodepletion with short-course low‑dose IL‑2 support versus investigator’s choice of approved therapies (e.g., nivolumab/relatlimab, anti‑PD‑1, ipilimumab, lifileucel, or chemotherapy). Key exclusions include mucosal/uveal melanoma, active CNS disease, significant autoimmune/cardiac comorbidities, active infections, and LDH >2× ULN.
ClinicalTrials.gov ID: NCT06743126
HealthScout AI summary: Single-arm study of lifileucel, an autologous tumor-infiltrating lymphocyte (TIL) therapy delivered after lymphodepleting chemotherapy and high‑dose IL‑2, in adults with advanced endometrial carcinoma (including carcinosarcoma) who have progressed after platinum chemotherapy and anti–PD‑1/PD‑L1 therapy, with at least one resectable lesion for TIL manufacture and one measurable lesion. Excludes uterine sarcomas and requires ECOG 0–1 and adequate organ function.
ClinicalTrials.gov ID: NCT06481592
HealthScout AI summary: Single-arm TIL therapy (lifileucel-based autologous tumor-infiltrating lymphocytes expanded ex vivo with IL-2) for children, adolescents, and young adults (≤21 years) with relapsed/refractory solid tumors lacking effective options, including sarcomas, primary CNS tumors, and melanoma. Patients undergo tumor resection for TIL manufacture, nonmyeloablative lymphodepletion, then a single TIL infusion with supportive care (typically IL-2); outcomes include safety and preliminary antitumor activity.
ClinicalTrials.gov ID: NCT06566092
HealthScout AI summary: Adults with unresectable stage IIIc/IV melanoma after 1–3 prior therapies (must include anti–PD‑1; BRAF/MEK if BRAF V600+) receive one-time autologous TIL therapy (lifileucel, polyclonal tumor-reactive T cells) following a reduced-dose fludarabine/cyclophosphamide lymphodepletion and up to 6 doses of IL‑2. Excludes uveal melanoma and active/untreated CNS disease; requires a resectable lesion for TIL harvest and ECOG 0–1.
ClinicalTrials.gov ID: NCT06151847
HealthScout AI summary: Adults with metastatic uveal melanoma (any prior therapy) or unresectable/metastatic UPS or DDLPS refractory to ≥1 systemic regimen receive autologous tumor-infiltrating lymphocyte therapy lifileucel (LN-144/LN-145) after nonmyeloablative lymphodepleting chemotherapy and followed by IL-2. Lifileucel consists of ex vivo–expanded, tumor-specific T cells (adoptive cell therapy) and is being studied here for safety/feasibility in these populations.
ClinicalTrials.gov ID: NCT05607095
HealthScout AI summary: This trial enrolls adults with metastatic, EGFR/ALK/ROS1-negative NSCLC who have progressed after prior immune checkpoint inhibitor and platinum chemotherapy, and who have a resectable tumor lesion and good performance status. Patients receive LN-145, an autologous tumor-infiltrating lymphocyte (TIL) therapy that reinfuses expanded tumor-reactive T cells following lymphodepleting chemotherapy, aiming to stimulate anti-tumor immunity.
ClinicalTrials.gov ID: NCT04614103
HealthScout AI summary: This trial enrolls patients with unresectable or metastatic melanoma (including those previously treated with PD-1 inhibitors or BRAF-targeted therapies), advanced head and neck squamous cell carcinoma, or locally advanced/metastatic non-small cell lung cancer, providing treatment with autologous tumor-infiltrating lymphocyte (TIL) products—lifileucel (LN-144/LN-145) or next-generation PD-1-selected LN-145-S1—either as monotherapy or in combination with immune checkpoint inhibitors (ICIs). Eligibility requires at least one resectable lesion and ECOG 0-1, and excludes active autoimmune disease or untreated symptomatic brain metastases.
ClinicalTrials.gov ID: NCT03645928
