Tumor Infiltrating Lymphocyte Therapy LN-145 Achieves Responses Among Patients With NSCLC

Iovance Biotherapeutics’ LN-145, an investigational tumor infiltrating lymphocyte (TIL) therapy, has achieved responses among patients with advanced post antiPD-1 non–small cell lung cancer (NSCLC) who were treated in the registrational phase 2 IOV-LUN-202 clinical trial (NCT04614103).¹

Among 23 patients who were treated in the trial as of the July 6, 2023, data cutoff, the objective response rate (ORR) was 26.1% (n = 6). One patient achieved a complete response (CR) and 5 patients achieved partial responses. The disease control rate was 82.6%. Furthermore, the range of the duration of response (DOR) was 1.4+ months to 9.7+ months; Iovance noted that the median DOR was not reached. Participants in the trial received LN-145 following a nonmyeloablative lymphodepletion regimen; after LN-145 infusion, patients received interleukin-2 (IL-2). In terms of safety, the company reported that the treatment-emergent adverse events observed in the trial have been consistent with expectations for NSCLC, nonmyeloablative lymphodepletion, and IL-2 administration.

This preliminary analysis was conducted in light of positive feedback Iovance received in a Type B Pre-Phase 3 meeting with the FDA. The company stated that in the meeting the agency indicated that IOV-LUN-202's design may allow for accelerated approval of LN-145 for the population of patients with advanced NSCLC who do not have genomic mutations in EGFR, ROS, or ALK; whose disease has progressed during or following chemotherapy and antiPD-1 therapy; and who have previously been treated with a minimum of 1 line of FDA-approved targeted therapy if indicated by other actionable tumor mutations. Advanced NSCLC was defined as unresectable or metastatic disease in this context. With reference to the meeting, Iovance stated that it expects it will have enrolled approximately 120 patients in IOV-LUN-202 in total by the second half of 2024.

LN-145 is additionally being evaluated in several cohorts in the phase 3 IOV-COM-202 clinical trial (NCT03645928), which also has cohorts evaluating Iovance’s LN-144 (Lifileucel) and LN-145-S1.² In January of this year, Iovance reported results from cohort 3A in IOV-COM-202. Cohort 3A is assessing LN-145 in combination with the antiPD-1 therapy pembrolizumab (Keytruda) for the treatment of patients with locally advanced or metastatic NSCLC who have previously received 3 or fewer lines of systemic therapy, excepting immune checkpoint inhibitors, or 4 or fewer lines of therapy if 2 or more lines were tyrosine kinase inhibitor (TKI) therapy for tumors with actionable mutations. Among 17 patients who were treated in this cohort, the ORR was 47% (n = 8). Iovance noted that patients in this cohort achieved responses regardless of their PD-L1 status. Furthermore, the subset of 5 patients who were treatment-naïve had an ORR of 80% (n = 4), the subset of 7 patients who had previously been treated with chemotherapy, but not antiPD-1 therapy had an ORR of 43% (n = 3), and the subset of 5 patients who had EGFR mutations and had previously been treated with TKI therapy had an ORR of 20% (n = 1). One of the patients in cohort 3A who had previously been treated with chemotherapy, but not antiPD-1 therapy and 1 of the patients who had EGFR mutations and had previously been treated with TKI therapy each achieved a CR. In terms of safety, results were consistent with Iovance’s other assessments of TIL therapies in combination with pembrolizumab.

Iovance Biotherapeutics stated that as of July 2023 it is still awaiting a planned meeting with the FDA originally announced in January 2023 to discuss the cohort 3A results from IOV-COM-202.^1,2 In the meeting, which is anticipated to take place before the end of the year, Iovance will discuss plans for a randomized confirmatory study to evaluate LN-145 in combination with pembrolizumab in patients with advanced NSCLC who do not have mutations in EGFR and who have not previously received treatment for their disease. Alongside the patients who receive the combination therapy, a separate arm in the trial will treat patients with pembrolizumab as a monotherapy for comparison. The proposed design includes a regimen of pembrolizumab and limited duration chemotherapy before administration of the combination therapy or monotherapy in responding patients.