On November 10, 2022 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies (tumor infiltrating lymphocyte, TIL, and peripheral-blood lymphocyte, PBL), reported updated clinical data for lifileucel in advanced melanoma during a rapid oral presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting (Press release, Iovance Biotherapeutics, NOV 10, 2022, View Source [SID1234624237]).

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Amod Sarnaik, M.D., Professor of Cutaneous Oncology and Immunology at H. Lee Moffitt Cancer Center, presenting author and lead C-144-01 trial investigator, stated, "We are excited to present the comprehensive clinical data on behalf of the C-144-01 investigators. The trial demonstrated a robust and clinically meaningful response rate and long-term durability following one-time treatment. Patients in this study were difficult to treat and lacked approved therapies after current standard of care. We hope to offer lifileucel to many more patients after initial progression on immune checkpoint inhibitors."

The oral presentation for the C-144-01 trial included efficacy data from 153 patients with advanced melanoma enrolled in Cohort 2 (n=66) and Cohort 4 (n=87) with a median study follow up of 36.5 months (data cut off July 15, 2022). All patients had progressed on or after immune checkpoint inhibitor (ICI) therapy and targeted BRAF/MEK inhibitor therapy where appropriate. There are no treatments approved by the U.S. Food and Drug Administration (FDA) for the C-144-01 study population. The current available care is chemotherapy (4-10% ORR; median overall survival [mOS] of 7-8 months).1-4

SITC C-144-01 Data Highlights for Pooled Analysis (36.5 Months Median Study Follow Up)

Heavily Pretreated Patient Population with Substantial Disease Burden: Patients had received a median of 3 lines of prior therapy (range 1-9), including anti-PD-1 therapy in 100% of patients (median: 2 lines, range 1-7) 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 (> 3 lesions: 83.9% vs. 65.2%) and a higher proportion of patients with elevated lactate dehydrogenase (LDH; 64.4% vs 40.9%), a well-known negative prognostic factor in melanoma.5

Clinically Meaningful Response Rate and Durability
Clinically Meaningful ORR and Deepening of Responses Over Time: The ORR assessed by an independent review committee (IRC) using RECIST v1.1 was 31.4% (95% CI: 24.1%-39.4%), with 9 complete responses (CRs) and 39 partial responses (PRs). 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 (Not Reached) and Durability at 2+ Years: The mDOR was not reached (estimated by Kaplan-Meier, or KM, method). Responses lasted for 24 months or greater in 41.7% of responders (47.8% of responders in Cohort 2; 36.0% of responders in Cohort 4).

Long-Term Benefit from One-Time Lifileucel Therapy: The DOR and overall survival (OS) KM plots show plateaus characteristic of immunotherapy, supporting the potential for long-term benefit from lifileucel therapy. Median (mOS) had not been reached (95% CI: 30.4-NR) in patients who achieved a response at first assessment (6 weeks). mOS in all patients was 13.9 months (95% CI: 10.6-17.8).

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 (SOD; tumor mass across locations) were correlated with ORR (P=0.008). Higher odds of response with lower tumor burden suggest that early intervention with lifileucel after ICI may maximize benefit.
Safety: Treatment-emergent adverse events (TEAEs) were consistent with the underlying disease and known AE profiles of nonmyeloablative lymphodepletion and interleukin-2 (IL-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 (Gen 2). Lifileucel was manufactured within specification in 94.7% of patients across Cohorts 2 and 4.
Friedrich Graf Finckenstein, M.D., Chief Medical Officer of Iovance, stated, "Our C-144-01 trial is the largest clinical trial of a cell therapy in advanced melanoma following anti–PD-1 therapy and the basis for our rolling BLA submission for lifileucel. We observed responses across the spectrum of patients with advanced melanoma, including early responses and deepening responses over time, following anti-PD-1 and anti-CTLA-4 therapy, and regardless of mutation and PD-L1 status. Given the correlation of lower tumor burden and response, we believe there is a strong rationale for treatment with lifileucel as soon as possible after initial progression on anti–PD-1 therapy. The potential for long-term benefit from one-time treatment with lifileucel is promising, as the overall survival data show the desired plateau of maintained benefit with immunotherapy, and include patients who are alive five years after treatment."

The C-144-01 results are available in the oral presentation slide deck on the Iovance corporate website. Data from the pivotal Cohort 4, supportive data from Cohort 2 and the pooled analysis of Cohorts 2 and 4 are part of a rolling Biologics License Application (BLA) submission to the FDA for lifileucel in advanced melanoma, which Iovance initiated in August 2022.

Investor Webcast on Thursday, November 10, 4:30 p.m. ET
Iovance will host a webcast on Thursday, November 10 at 4:30 p.m. ET to discuss clinical data updates for lifileucel in advanced melanoma. Iovance senior leadership will be joined by the following key opinion leaders and principal investigators in Iovance clinical studies: Amod Sarnaik; Allison Betof Warner, M.D., Ph.D., Assistant Attending Physician and Melanoma Medical Oncologist, Memorial Sloan Kettering Cancer Center; Miguel Perales, M.D., Chief, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center; and Martin McCarter, M.D., Surgical Director for the Esophageal and Gastric Multidisciplinary Clinic, Vice Chair for Strategy and Program Development Department of Surgery, UCHealth Cancer Care – Anschutz Medical Campus – University of Colorado Cancer Center. The live and archived webcast can be accessed in the Investors section of the company’s website here: View Source