FDA Lifts Clinical Hold on Trial Investigating LN-145 in NSCLC

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:

• Cohort 1: Patients with a PD-L1 tumor proportion score (TPS) of less than 1% prior to checkpoint inhibitor treatment and patients with no historical TPS available
• Cohort 2: Patients with a PD-L1 TPS of at least 1% prior to checkpoint inhibitor treatment
• Cohort 3: Patients unable to safely undergo a surgical tumor resection for TIL generation, irrespective of PD-L1 TPS status
• Cohort 4: Patients who meet all inclusion/exclusion criteria, except the requirement to have documented disease progression, are allowed to elect to undergo the tumor harvest procedure and TIL production prior to disease progression on their current anticancer treatment
• Cohort Retreatment Cohort 55: Patients previously treated with LN-145 in cohorts 1 to 4

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.

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://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 4, 2024. https://ir.iovance.com/news-releases/news-release-details/iovance-biotherapeutics-announces-clinical-program-update-ln-145
3. Autologous LN-145 in patients with metastatic non-small-cell lung cancer. ClinicalTrials.gov. Updated December 19, 2023. Accessed March 4, 2024. https://www.clinicaltrials.gov/study/NCT04614103
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 4, 2024. https://ir.iovance.com/news-releases/news-release-details/iovance-biotherapeutics-announces-regulatory-and-clinical-0