Iovance Biotherapeutics announces updated clinical data for lifileucel

Iovance Biotherapeutics announced updated clinical data for lifileucel in advanced melanoma during a rapid oral presentation at the Society for Immunotherapy of Cancer Annual Meeting. The oral presentation for the C-144-01 trial included efficacy data from 153 patients with advanced melanoma enrolled in Cohort 2 and Cohort 4 with a median study follow up of 36.5 months. All patients had progressed on or after immune checkpoint inhibitor therapy and targeted BRAF/MEK inhibitor therapy where appropriate. There are no treatments approved by the U.S. Food and Drug Administration for the C-144-01 study population. The current available care is chemotherapy. SITC C-144-01 Data Highlights for Pooled Analysis: Heavily Pretreated Patient Population with Substantial Disease Burden: Patients had received a median of 3 lines of prior therapy, including anti-PD-1 therapy in 100% of patients and anti-CTLA-4 therapy in 81.7% of patients, with prior combination anti-PD-1 and anti-CTLA-4 therapy received in 53.6% of patients. Baseline disease characteristics were generally similar between Cohorts 2 and 4. However, Cohort 4 patients showed both a higher disease burden and a higher proportion of patients with elevated lactate dehydrogenase, a well-known negative prognostic factor in melanoma. Clinically Meaningful ORR and Deepening of Responses Over Time: The ORR assessed by an independent review committee using RECIST v1.1 was 31.4%, with 9 complete responses and 39 partial responses. The median time from lifileucel infusion to best response was 1.5 months, and responses deepened over time. Initial PRs converted to CRs in 7 patients, as late as 2+ years post-lifileucel, including 1 conversion to CR in approximately 10 months since the initial data analysis in the abstract. mDOR and Durability at 2+ Years: The mDOR was not reached. Responses lasted for 24 months or greater in 41.7% of responders. Long-Term Benefit from One-Time Lifileucel Therapy: The DOR and overall survival KM plots show plateaus characteristic of immunotherapy, supporting the potential for long-term benefit from lifileucel therapy. Median had not been reached in patients who achieved a response at first assessment. mOS in all patients was 13.9 months. Responses Across All Subgroups: Responders to lifileucel included patients with ICI primary-resistant disease, those who received prior anti-CTLA-4 therapy and/or targeted therapies, and responses were observed regardless of PD-L1 status. LDH and target lesion sum of diameters were correlated with ORR. Higher odds of response with lower tumor burden suggest that early intervention with lifileucel after ICI may maximize benefit. Safety: Treatment-emergent adverse events were consistent with the underlying disease and known AE profiles of nonmyeloablative lymphodepletion and interleukin-2. Incidence of TEAEs decreased rapidly within the first 2 weeks after lifileucel infusion. 94.7% Manufacturing Success Rate: All patients in both cohorts received the same lifileucel treatment using Iovance’s proprietary 22-day manufacturing process. Lifileucel was manufactured within specification in 94.7% of patients across Cohorts 2 and 4.