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

Preliminary data from the IOV-LUN-202 trial that were presented in July 2023 highlighted an objective response rate (ORR) of 26.1% per RECIST v1.1 criteria among 23 patients with NSCLC who were treated with the LN-145 regimen, which included 1 complete response (CR) and 5 partial responses.

The FDA has placed a clinical hold on the phase 2 IOV-LUN-202 trial (NCT04614103), assessing LN-145 tumor-infiltrating lymphocyte (TIL) therapy in patients with advanced non–small cell lung cancer (NSCLC) following reports of a fatal serious adverse effect (SAE) potentially associated with the trial’s lymphodepleting pre-conditioning regimen, according to a press release from Iovance Biotherapeutics, Inc.¹

As part of the clinical hold, investigators will not enroll any additional patients on the IOV-LUN-202 trial. Additionally, investigators will continue to monitor and follow up with those who already received a dose of the study regimen based on trial protocol. Those whose tumors were previously resected may continue treatment with LN-145 with the implementation of additional risk mitigation strategies and precautions.

“Iovance remains dedicated to addressing a significant unmet medical need for patients with advanced NSCLC, who have poor prognosis following disease progression and limited treatment options,” Friedrich Graf Finckenstein, MD, chief medical officer at Iovance, said.¹ “We will work with the FDA to safely resume enrollment in the IOV-LUN-202 trial as soon as possible.”

Preliminary data from the IOV-LUN-202 trial that were presented in July 2023 highlighted an objective response rate (ORR) of 26.1% per RECIST v1.1 criteria among 23 patients with NSCLC who were treated with the LN-145 regimen, which included 1 complete response (CR) and 5 partial responses.² Additionally, the duration of response (DOR) ranged from 1.4+ to 9.7+ months, and the disease control rate was 82.6%. At the time of the analysis, investigators observed treatment-related AEs that were comparable with those associated with non-myeloablative lymphodepletion and interleukin-2 (IL-2).

Findings from an updated analysis in November 2023 indicated that there was a higher proportion of sustained responses, as well as a DOR of more than 6 months for 71% of those with a confirmed response in the IOV-LUN-202 trial.¹

Investigators of the IOV-LUN-202 trial are evaluating LN-145 TIL therapy across multiple cohorts of patients with NSCLC. The trial includes patients with a PD-L1 TPS of less than 1% or 1% or higher, those who are unable to safely receive a surgical tumor resection for TIL generation, and those previously treated with LN-145 in the aforementioned cohorts.

As part of the study regimen, investigators retrieved a tumor sample from each patient to expand the population of TILs. Additionally, patients received an infusion of autologous LN-145 followed by IL-2 after the completion of lymphodepleting chemotherapy.

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

Patients 18 to 70 years old with histologically confirmed stage IV NSCLC without any EGFR, ALK, or ROS mutations were eligible for enrollment on the trial. Additional eligibility criteria included having at least 1 resectable lesion for TIL production, at least 1 measurable lesion per RECIST v1.1 guidelines, adequate organ and pulmonary function, and an ECOG performance status of 0 or 1.

Those with EGFR, ALK, or ROS driver mutations or who had untreated and symptomatic brain metastases were unable to enroll on the trial. Patients were also unsuitable for enrollment if they had any form of primary immunodeficiency.

References

1. Iovance Biotherapeutics announces clinical program update for LN-145 in non-small cell lung cancer. News release. Iovance Biotherapeutics. December 27, 2023. Accessed January 2, 2024. https://bit.ly/3S5rhm5
2. 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 January 2, 2024. https://bit.ly/48yc3ey