FDA Places Clinical Hold on Trial of LN-45 in NSCLC


Following a patient death in the phase 2 IOV-LUN-202 trial, the FDA has issued a clinical hold.

Holographic concept of lung cancer display, lung disease, treatment of lung cancer: © catalin - stock.adobe.com

Holographic concept of lung cancer display, lung disease, treatment of lung cancer: © catalin - stock.adobe.com

  • The FDA has placed a clinical hold on the IOV-LUN-202 trial (NCT04614103) following a grade 5 fatal adverse event (AE).1
  • IOV-LUN-202 is a phase 2 study investigating LN-45, a tumor infiltrating lymphocyte (TIL) for the treatment of non–small cell lung cancer (NSCLC).
  • The clinical hold has no impact on other clinical trials being done by Iovance or license applications.

The phase 2 IOV-LUN-202 trial investigating the LN-45 TIL therapy for the treatment of patients with advanced NSCLC has been placed on clinical hold by FDA following a the death of a patient death. The fatal AE is potentially related to the non-myeloablative lymphodepletion preconditioning regimen.1

“Iovance remains dedicated to addressing a significant unmet medical need for patients with advanced NSCLC, who have poor prognosis following disease progression and limited treatment options. We will work with the FDA to safely resume enrollment in the IOV-LUN-202 trial as soon as possible,” said Friedrich Graf Finckenstein, MD, chief medical officer of Iovance, in a press release.

Data from a preliminary analysis was announced in July 2023. The findings reported an objective response rate (ORR) of 26.1% (n = 6) and a disease control rate (DCR) of 82.6%. There were 5 partial responses and 1 complete response. The duration of response (DOR) was not yet met.2

In other reported clinical trial results, treatment-emergent AEs have been consistent with disease progression, as well as and the known safety profiles of non-myeloablative lymphodepletion and interleukin-2, according to Iovance.1

IOV-LUN-202 has an estimated enrollment of 170 patients with histologically or pathologically confirmed metastatic stage IV NSCLC without EGFR, ROS, or ALK mutations. Patients must have had disease progression following at least 1 prior line of therapy. The primary end point is ORR, and the secondary end points include complete response rate, DOR, DCR, progression-free survival, overall survival, incidence of AEs, and core biopsies.3

Four cohorts were incorporated in the study. These included:

  • Cohort 1: Patients with tumors not expressing PD-L1 and tumor proportion score (TPS) < 1% before immune checkpoint inhibitor (ICI) treatment, or patients with no available historical TPS for PD-L1 expression.
  • Cohort 2: Patients with tumors expressing PD-L1 TPS ≥1% prior to ICI treatment.
  • Cohort 3: Patients with unresectable tumors regardless of PD-L1 TPS prior to ICI treatment.
  • Cohort 4: Patients without documented disease progression following prior treatment and have elected to undergo tumor harvesting procedure and TIL production, regardless of PD-L1 expression.

There is also an experimental retreatment cohort of patients from any of the 4 core cohorts who were previously treated with LN-45.

Iovance Biotherapeutics, LN-45’s manufacturer, is also the manufacturer of lifileucel. The priority review of the biologics license application for lifileucel (LN-144 ) is not affected, and the Prescription Drug User Fee Act target date of February 24, 2024, is still in place.

1. Iovance Biotherapeutics announces clinical program update for LN-145 in non-small cell lung cancer. News release. Iovance Biotherapeutics. December 27, 2023. Accessed January 4, 2024. http://tinyurl.com/2tx2dw6s
2. Iovance Biotherapeutics abnnounces regulatory and clinical updates for TIL therapy in advanced non-small cell lung cancer. News release. Iovance Biotherapeutics. July 10, 2023. Accessed January 4, 2024. http://tinyurl.com/5azt94x2
3. Autologous LN-145 in patients with metastatic non-small-cell lung cancer. ClinicalTrials.gov. Updated December 19, 2023. Accessed January 4, 2024. https://clinicaltrials.gov/study/NCT04614103
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