FDA Lifts Partial Clinical Hold on Phase II Trial of Novel Tumor Infiltrating Lymphocyte Cell Therapy for NSCLC

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The FDA has removed a partial clinical hold on a Phase II trial evaluating Iovance Biotherapeutics’ novel tumor infiltrating lymphocyte (TIL) cell therapy LN-145 in patients with advanced non–small cell lung cancer (NSCLC).1 The FDA halted the IOV-LUN-202 trial (NCT04614103) in December 2023 following reports of a grade 5 serious adverse event (AE) that may have been linked to treatment with the non-myeloablative lymphodepletion preconditioning regimen.2

“In collaboration with the FDA and an independent data monitoring committee, Iovance developed additional safety measures and monitoring,” Iovance Biotherapeutics stated in a press release. “Upon reviewing this proposal, the FDA has cleared Iovance to resume patient enrollment in IOV-LUN-202.”

TILs are naturally occurring white blood cells in the immune system that can recognize and destroy cancer cells. For treatment with TIL cell therapy, the TILs are removed from a patient’s tumor and enhanced in a laboratory before being infused back into the patient to help the immune system recognize and eliminate the cancer cells.3

The open-label, multi-cohort, multicenter, nonrandomized IOV-LUN-202 trial is evaluating LN-145 in patients with unresectable or metastatic NSCLC without EGFR, ROS or ALK genomic mutations who received prior treatment with chemotherapy and anti-programmed cell death protein (PD)-1 therapy, as well as a minimum of one line of an approved targeted therapy if indicated by other actionable tumor mutations. This patient population has a poor prognosis with few treatment options, translating to a real-world overall survival (OS) of fewer than six months.3

Exclusion criteria included presence of symptomatic, untreated brain metastases; prior administration of an allogeneic organ transplant or prior cell therapy within the past 20 years; having any form of primary immunodeficiency; or an additional primary malignancy over the past three years.3

Before administration of LN-145, patients enrolled in the trial receive lymphodepletion comprised of cyclophosphamide and fludarabine. After a single infusion of the TIL cell therapy, patients also are administered interleukin-2 (IL-2).

The primary endpoint of IOV-LUN-202 is objective response rate (ORR) per central review, with secondary endpoints that include complete response (CR) rate, duration of response (DOR), disease control rate (DCR), progression-free survival, OS, and safety.

Preliminary trial data released in July 2023 found that among evaluable patients (n = 23) administered LN-145, the ORR was 26.1%, with one patient achieving a CR and five achieving a partial response, and a DCR of 82.6%. At the data cutoff date, median DOR was not yet reached (1.4+ months–9.7+ months).4

In terms of safety, treatment-emergent AEs were consistent with the known safety profiles of lymphodepletion and IL-2.

“Preliminary data from the IOV-LUN-202 trial support the potential benefit of one-time TIL therapy, including the opportunity for more durable responses than available second line chemotherapies,” Iovance Biotherapeutics stated in a press release. “An updated analysis in November of 2023 showed additional ongoing responses and duration of response greater than six months for 71% of the confirmed responders in the trial.”1

Iovance stated that enrollment of approximately 120 patients in the IOV-LUN-202 registrational cohorts is expected to be completed in 2025.


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 5, 2024. https://ir.iovance.com/news-releases/news-release-details/iovance-biotherapeutics-announces-fda-has-lifted-clinical-hold

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 5, 2024. https://ir.iovance.com/news-releases/news-release-details/iovance-biotherapeutics-announces-clinical-program-update-ln-145

3. Iovance Biotherapeutics. A Phase 2 Clinical Study for Metastatic Non-Small Cell Lung Cancer (NSCLC). Webpage. Updated 2023. Accessed March 5, 2024. https://www.lungcelltherapy.com/

4. 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 5, 2024. https://ir.iovance.com/news-releases/news-release-details/iovance-biotherapeutics-announces-regulatory-and-clinical-0

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