Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors

Conditions

• Metastatic Melanoma
• Non-small Cell Lung Cancer
• Squamous Cell Carcinoma of the Head and Neck

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Lifileucel — BIOLOGICAL
  A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor-infiltrating lymphocytes (TIL). After NMA-LD, patients receive lifileucel, followed by aldesleukin administration. Lifileucel will be administered to patients once (on Day 0) during the study.
• LN-145 — 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 their autologous TIL (LN-145) followed by aldesleukin administration. TIL will be administered to patients once (on Day 0) during the study.
• Pembrolizumab — DRUG
  Humanized antibody. Pembrolizumab will be administered after tumor resection and will continue every 3 weeks or every 6 weeks for up to 2 years.
• LN-145-S1 — BIOLOGICAL
  A tumor sample is resected from each patient and cultured ex vivo to expand the population of TIL, then TIL with high levels of PD-1 surface expression are selected. After NMA-LD, patients receive their autologous PD-1-selected TIL (LN-145-S1), followed by aldesleukin administration. TIL will be administered to patients once (on Day 0) during the study.
• Ipilimumab — DRUG
  Monoclonal antibody Ipilimumab will be administered as a single dose prior to tumor resection.
• Nivolumab — DRUG
  Monoclonal antibody. Nivolumab will be administered once prior to tumor resection. The second dose will be administered prior to starting NMA-LD and will continue every 4 weeks for up to 2 years.
• Nivolumab-relatlimab — DRUG
  Monoclonal antibody (nivolumab) and monoclonal antibody (relatlimab). Nivolumab-relatlimab will be administered after tumor resection and will continue every 4 weeks for up to 2 years.
• Cisplatin — DRUG
  Cisplatin administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
• Carboplatin — DRUG
  Carboplatin administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
• Paclitaxel — DRUG
  Paclitaxel administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
• Nab paclitaxel — DRUG
  Nab-Paclitaxel administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles.
• Pemetrexed — DRUG
  Pemetrexed administered intravenously at the protocol-defined dose every 3 weeks for up to 4 cycles. Optional continuation maintenance every 3 weeks, if applicable.

Study Details

A prospective, open-label, multi-cohort, non-randomized, multicenter Phase 2 study evaluating adoptive cell therapy (ACT) with TIL \[LN-144/LN-145 (lifileucel)\] in combination with immune checkpoint inhibitors or TIL \[LN-144/LN-145 (lifileucel) and LN-145-S1\] as a single agent therapy.

Key Dates

Start date

May 7, 2019

Status verified

May 2026

Primary completion

Feb 20, 2026

Completion

Feb 20, 2026

Study Design

Enrollment

225 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Cohort 1A
  Lifileucel (LN-144) regimen in combination with pembrolizumab in patients with Stage IIIC to IV unresectable or metastatic melanoma with ≤ 3 prior lines of systemic therapy, excluding immune checkpoint inhibitors (ICI).
• Experimental: Cohort 1B
  LN-145-S1 regimen in patients with Stage IIIC or Stage IV unresectable or metastatic melanoma, who have previously received systemic therapy with a PD-1 blocking antibody. If the tumor is proto-oncogene B-Raf (BRAF) V600 mutation positive, patients must have received a BRAF inhibitor with or without a mitogen-activated extracellular signal-related kinase (MEK) inhibitor.
• Experimental: Cohort 1C
  Lifileucel (LN-144 Generation 3 \[Gen 3\]) regimen in patients with Stage IIIC or Stage IV unresectable or metastatic melanoma, who have previously received systemic therapy with a PD-1 blocking antibody. If the tumor is BRAF V600 mutation positive, patients must have received BRAF inhibitor with or without a MEK inhibitor.
• Experimental: Cohort 2A
  Lifileucel (LN-145) regimen in combination with pembrolizumab in patients with advanced, recurrent, or metastatic HNSCC, with ≤ 3 prior lines of systemic therapy, excluding ICIs.
• Experimental: Cohort 3A
  Lifileucel (LN-145) regimen in combination with pembrolizumab in patients with locally advanced or metastatic (Stage III or Stage IV) non-small-cell lung cancer (NSCLC) with ≤ 3 prior lines of systemic therapy, excluding ICIs, or ≤ 4 lines if 2 or more of the lines are tyrosine kinase inhibitor (TKI) therapy for those with tumors that harbored actionable mutations (eg, EGFR, ALK, ROS).
• Experimental: Cohort 3B
  Lifileucel (LN-145) regimen ent in patients with Stage III or Stage IV NSCLC, who have previously received 1-3 lines of prior systemic therapy. Patients with known oncogene drivers (eg, EGFR, ALK, ROS) who have mutations that are sensitive to targeted therapies are not required to have received prior systemic therapy with ICIs.
• Experimental: Cohort 3C
  Lifileucel (LN-145) regimen in combination with ipilimumab and nivolumab in patients with Stage III or Stage IV NSCLC who have previously received 1 line of ICI monotherapy. No other systemic therapy for metastatic disease is allowed. Prior chemoradiation and/or chemotherapy in the adjuvant and/or neo-adjuvant settings are allowed.
• Experimental: Cohort 3D
  Lifileucel regimen in combination with pembrolizumab with or without pemetrexed, given after tumor resection then 4 cycles of frontline platinum doublet chemotherapy plus pembrolizumab, in patients with Stage IV NSCLC without EGFR, ALK, or ROS1 driver mutations, who have had no prior therapy for advanced disease.
• Experimental: Cohort 3E
  Lifileucel regimen in combination with pembrolizumab with or without pemetrexed, given after 4 cycles of frontline platinum doublet chemotherapy plus pembrolizumab with tumor resection between any 2 cycles, in patients with Stage IV NSCLC without EGFR, ALK, or ROS1 driver mutations.
• Experimental: Cohort 1D
  Lifileucel (LN-144) regimen in combination with nivolumab-relatlimab in patients with Stage IIIC to IV unresectable or metastatic (advanced) melanoma who have had no prior therapy for advanced disease.

Primary Outcome Measure

Objective Response Rate [ Time Frame: Up to 60 months ]

Locations (20)

Find similar trials in La Jolla, CA

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