FDA Lifts Clinical Hold on LN-145 Phase 2 Trial Enrollment in NSCLC

The FDA originally placed a partial clinical hold on the IOV-LUN-202 trial (NCT04614103) in December 2023 after investigators reported a fatal serious adverse effect (SAE) that was potentially related to the study’s lymphodepleting preconditioning regimen.

The FDA has lifted a partial clinical hold on the phase 2 IOV-LUN-202 trial (NCT04614103) assessing treatment with the tumor-infiltrating lymphocyte (TIL) cell therapy LN-145 among patients with non–small cell lung cancer (NSCLC), according to a press release from Iovance Biotherapeutics, the developers of LN-145.¹

Developers worked alongside the FDA and an independent data monitoring committee to implement new safety measures and monitoring for the trial. The regulatory agency cleared developers to continue patient enrollment for the trial after reviewing this proposal.

The FDA originally placed a partial clinical hold on the IOV-LUN-202 trial in December 2023 after investigators reported a fatal serious adverse effect (SAE) that was potentially related to the study’s lymphodepleting preconditioning regimen.² As part of the clinical hold, investigators were prohibited from enrolling additional patients on the trial and monitored those who had already received a dose of study treatment based on protocol. Patients with previously resected tumors were eligible to continue receiving LN-145 with additional risk mitigation strategies and precautions in place.

According to preliminary data from the phase 2 IOV-LUN-202 trial highlighted in July 2023, treatment with LN-145 produced an overall response rate (ORR) of 26.1% (n = 6/23) among evaluable patients with NSCLC, which included 5 partial responses (PRs) and 1 complete response (CR).³ Additionally, the disease control rate (DCR) rate was 82.6%. The median duration of response (DOR) was not reached at the time of the analysis, with responses lasting from 1.4+ months to 9.7+ months. Based on an updated analysis in November 2023, 71% of patients with a confirmed response had responses that were sustained for more than 6 months.¹

The safety profile of LN-145 in the IOV-LUN-202 trial was comparable with the known AE profiles of non-myeloablative lymphodepletion and interleukin-2.³

Investigators of the IOV-LUN-202 trial are assessing treatment with LN-145 among patients with previously treated advanced NSCLC who have no EGFR, ROS, or ALK genomic mutations. According to the developers, the trial will include an approximate population of 120 patients across its registrational cohorts in 2025.

The IOV-LUN-202 trial includes 5 experimental cohorts, including patients without PD-L1 expression, those with a PD-L1 tumor proportion score of 1% or higher, those who are unable to safely receive surgery for TIL generation, those without documented disease progression, and patients who received prior treatment with LN-145 in any of the groups.

Tumor samples will be resected from each patient and cultured ex vivo for expanding TILs as part of the study regimen. Additionally, investigators will administer lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by infusion with autologous LN-145 TIL therapy and IL-2.

The trial’s primary end point is ORR based on RECIST v1.1 criteria. Secondary end points include CR rate, DOR, DCR, progression-free survival, overall survival, AEs, and core biopsies.

Patients 18 to 70 years old with histologically or pathologically confirmed metastatic stage IV NSCLC without EGFR, ALK, or ROS genomic alterations can enroll on the trial. Additional eligibility criteria include having adequate organ and pulmonary function, an ECOG performance status of 0 or 1, and prior systemic therapy in the adjuvant or neoadjuvant setting. Those with actionable mutations apart from the previously described types are eligible for enrollment if they have received an additional line of treatment with an appropriate targeted therapy as approved by a health authority.

Those with symptomatic, untreated brain metastases or any form of primary immunodeficiency are unable to enroll on the study.

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, Inc. March 4, 2024. Accessed March 4, 2024. https://tinyurl.com/4skfh324
2. Iovance Biotherapeutics announces clinical program update for LN-145 in non-small cell lung cancer. News release. Iovance Biotherapeutics, Inc. December 27, 2023. Accessed March 4, 2024. https://bit.ly/3S5rhm5
3. Iovance Biotherapeutics announces regulatory and clinical updates for TIL therapy in advanced non-small cell lung cancer. News release. Iovance Biotherapeutics, Inc. July 10, 2023. Accessed March 4, 2024. https://bit.ly/48yc3ey