FDA Lifts Clinical Hold on TIL Therapy Trial in Lung Cancer

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

• The phase 2 IOV-LUN-202 (NCT04614103) trial was put on partial clinical hold in December 2023 following a patient death.
• Iovance Biotherapeutics, the manufacturer of the study drug LN-145, a tumor infiltrating lymphocyte (TIL) cell therapy for the treatment on non-small cell lung cancer (NSCLC), worked with the FDA and an independent review committee to address safety concerns.
• Now that the clinical hold has been lifted, the trial can resume patient enrollment.

The FDA has announced it will lift the partial clinical hold on the IOV-LUN-202 trial investigating the TIL cell therapy LN-145 for the treatment of NSCLC following collaboration with the FDA and an independent data monitoring committee to develop additional safety and monitoring measures.¹

In December 2023, the FDA placed the IOV-LUN-202 on a partial clinical hold following a patient death potentially related to the nonmyeloablative lymphodepletion preconditioning regimen.²

About the IOV-LUN-202 Trial of LN-145 TIL in NSCLC

IOV-LUN-202 is investigating LN-145 for the treatment of patients with advanced unresectable or metastatic NSCLC without EGFR, ROS, or ALK mutations. Patients must have been previously treated with chemotherapy, an anti-PD-1 agent, and at least 1 additional line of targeted therapy for those with actionable genetic mutations. The enrollment of approximately 120 patients is expected to be completed by 2025.¹

Initial findings were released in July 2023 and showed an overall response rate (ORR) of 26.1%, consisting of 1 complete response and 5 partial responses. The disease control rate (DCR) was 82.6%. The median duration of response (DOR) was not reached, and it ranged from 1.4+ to 9.7+ months.^2,3 Updated findings from November 2023 showed that 71% of confirmed responders had ongoing responses and confirmed DORs greater than 6 months.¹

The study’s primary end point is ORR, and the secondary end points include complete response rate, DOR, DCR, progression-free survival, overall survival, incidence of adverse events, and core biopsies.⁴

Four cohorts are included in the study, including:

• Cohort 1: Patients with tumors that do not express PD-L1 and a tumor proportion score (TPS) less than 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 greater than or equal to 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.

REFERENCES:

1. Iovance Biotherapeutics announces FDA has lifted clinical hold on the IOV-LUN-202 registrational trial in non-small cell lung cancer. News release. Iovance Biotherapeutics. March 4, 2024. Accessed March 4, 2024. https://tinyurl.com/25p6jrpw

2. Iovance Biotherapeutics announces clinical program update for LN-145 in non-small cell lung cancer. News release. Iovance Biotherapeutics. December 27, 2023. Accessed March 4, 2024. http://tinyurl.com/2tx2dw6s

3. Iovance Biotherapeutics announces regulatory and clinical updates for TIL therapy in advanced non-small cell lung cancer. News release. Iovance Biotherapeutics. July 10, 2023. Accessed March 4, 2024. https://tinyurl.com/227h3wr4

4. Autologous LN-145 in patients with metastatic non-small-cell lung cancer. ClinicalTrials.gov. Updated December 19, 2023. Accessed March 4, 2024. https://clinicaltrials.gov/study/NCT04614103