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The partial clinical hold placed on the phase 2 IOV-LUN-202 trial of LN-145 in non–small cell lung cancer has been lifted by the FDA.
The FDA has lifted the partial clinical hold placed on the phase 2 IOV-LUN-202 trial (NCT04614103) evaluating LN-145 in patients with advanced non–small cell lung cancer (NSCLC).1
In December 2023, the FDA placed the clinical hold on the study investigating the autologous tumor infiltrating lymphocyte (TIL) cell therapy following a reports of a grade 5 serious adverse effect (AE) that was potentially related to the non-myeloablative lymphodepletion preconditioning regimen.2
Additional safety measures and monitoring were implemented by Iovance Biotherapeutics—the developer of LN-154—–following consultation with the FDA and an independent data monitoring committee. Patient enrollment is now allowed to resume.1
The open-label, multi-cohort, multicenter, nonrandomized IOV-LUN-202 trial is enrolling patients with histologically or pathologically confirmed, unresectable or metastatic, stage IV NSCLC that does not harbor EGFR, ROS, or ALK mutations. Prior treatment with chemotherapy and anti–PD-1 therapy, as well as at least 1 additional line of an approved targeted therapy if indicated by other actionable mutations, is required.1,3
Other key inclusion criteria include at least 1 resectable lesion for TIL production, as well as at least 1 remaining measurable lesion per RECIST v1.1 criteria; an ECOG performance status of 0 or 1; and adequate organ and pulmonary function.3
Patients are being excluded if they have symptomatic, untreated brain metastases; received an allogeneic organ transplant or prior cell therapy within the past 20 years; have any form of primary immunodeficiency; or had another primary malignancy in the past 3 years.
Prior to receiving LN-145, enrolled patients are undergoing lymphodepletion consisting of cyclophosphamide and fludarabine. Following a single infusion of LN-145, patients are also receiving interleukin-2 (IL-2).
The study is comprised of 5 cohorts:
The study’s primary end point is objective response rate (ORR) per central review in cohorts 1 and 2, and per investigator assessment in cohorts 3 through 5. Secondary end points include complete response (CR) rate, duration of response (DOR), disease control rate (DCR), progression-free survival, overall survival, and safety.
Preliminary data from IOV-LUN-202 reported in July 2023 showed that evaluable patients treated with LN-145 (n = 23) experienced an ORR of 26.1%, including 1 patient who had a CR and 5 who had a partial response. Additionally, the DCR was 82.6%. At data cutoff, the median DOR was not yet reached (range, 1.4+ months–9.7+ months).4
Treatment-emergent AEs were consistent with the known safety profiles of lymphodepletion and IL-2.