Clinical Trials

Date: 2018-10-11

Type of information: Results

phase: 2

Announcement: results

Company: Lion Biotechnologies (USA - CA), now Iovance Biotherapeutics (USA - CA)

Product: lifileucel - LN-144

Action mechanism:

• cell therapy/immunotherapy product/tumor infiltrating lymphocytes. LN-144 is an autologous cell therapy of tumor-infiltrating lymphocytes (TIL) derived from the patient's own tumor and is based on TIL therapy regimens developed at the National Cancer Institute (NCI).

Disease: metastatic melanoma

Therapeutic area: Cancer - Oncology

Country: France, Hungary, Spain, Switzerland, UK, USA

Trial details:

• The purpose of the phase 2 study is to evaluate the safety, efficacy and feasibility of autologous TIL infusion (LN-144). The trial's primary endpoints include safety, and feasibility of LN-144 production using Lion's central manufacturing process. Secondary outcome measures include an additional feasibility measure of number of patients successfully infused with LN-144 and best overall response rate.
• Cohorts one and two will enroll 20 patients each and cohort three is a re-treatment cohort for a second LN-144 infusion in ten patients. (NCT02360579)

Latest news:

• • On October 11, 2018, Iovance Biotherapeutics reported results from an FDA End of Phase 2 meeting and provided a corporate update. FDA has acknowledged the potential acceptability of a single-arm cohort for registration. FDA has further acknowledged that conduct of a randomized Phase 3 trial may not be feasible in its intended population of advanced melanoma patients who have been treated with at least one systemic therapy including a PD-1 blocking antibody and if BRAF V600 mutation positive, a BRAF inhibitor or BRAF inhibitor with MEK inhibitor and is not required for initial registration of lifileucel.
• A new cohort of 80-100 patients in C-144-01 will be enrolled with a prospective definition of the primary endpoint of ORR to be read out by a Blinded Independent Review Committee (BIRC) to support registration of lifileucel. This new cohort, which the company refers to as Cohort 4, will be initiated in early 2019 and is expected to be fully enrolled by late 2019/early 2020. BLA submission to FDA is expected in the second half of 2020.
• Iovance was granted a Regenerative Medicine Advanced Therapy (RMAT) designation for lifileucel in advanced melanoma based on data provided to the FDA from the C-144-01 study.
• The company also reported that data from 46 patients of Cohort 2 of trial C-144-01 will be provided at SITC 2018. For these 46 patients, an objective response rate (ORR) of 37% has been observed in the cohort, with duration of response (DOR) ranging from 1.3+ to 14+ months depending on time of enrollment. The ORR includes one (1) complete response and 16 partial responses, six (6) of which are unconfirmed and pending patient’s upcoming second assessments. Enrollment in the global Phase 2 metastatic melanoma study, C-144-01, has reached the predefined sample size. Enrollment into the existing Cohort 2 will be closed and a new Cohort 4 will be initiated in early 2019. The company plans on initiating enrollment into Cohort 4 in early 2019 and expects to fully enroll the necessary patients into Cohort 4 by late 2019/early 2020. BLA submission is expected in the second half of 2020.
•   • On June 7, 2018, Iovance Biotherapeutics announced that the first patient was dosed in the ongoing C-144-01 Phase 2 trial of LN-144 (lifileucel) for the treatment of patients with metastatic melanoma at a clinical trial site in the United Kingdom. In December 2017, the company announced that the Generation 2 manufacturing process, with a duration of 22 days, was selected and all studies were shifted to utilize that method of manufacturing. The company has manufacturing capability in both the US and EU. This is the first patient treated with TIL developed in an EU-based manufacturing facility.
• C-144-01 is a Phase 2 multicenter study evaluating the safety and efficacy of autologous tumor infiltrating lymphocytes (lifileucel), Iovance’s lead product candidate for treatment of patients with metastatic melanoma. The study is currently enrolling in the United States and Europe. To date, Iovance has over 25 active clinical sites in the United States and Europe. The sample size for enrollment was increased to 85 for this study.
• • On November 9, 2017, Iovance Biotherapeutics announced early efficacy and safety data from Cohort 2 of the ongoing Phase 2 LN-144 metastatic melanoma trial (C-144-01). These data, being presented at the Society for Immunotherapy of Cancer (SITC) 32nd Annual Meeting in National Harbor, Maryland, show that administration of the company’s Generation 2 (Gen 2) manufacturing process in nine efficacy-evaluable metastatic melanoma patients resulted in a disease control rate (DCR) of 78%, which includes 3 confirmed partial responders (PRs) and a fourth PR awaiting confirmation. These patients had four median prior therapies. The Gen 2 manufacturing process reduces the process time to 22 days and the cell product is cryopreserved for ease of administration and handling.
• Preliminary efficacy data from nine patients in Cohort 2 shows a DCR of 78% including three partial responses and a fourth awaiting confirmation. Preliminary data to date show that the safety profile of Gen 2 LN-144 therapy is similar to Gen 1 LN-144 therapy previously presented at ASCO 2017. The most common adverse events reported were pyrexia, anaemia and nausea.
• • On June 5, 2017, Lion Biotechnologies announced a poster presentation of additional data from 16 patients enrolled in the first cohort of its ongoing Phase 2 study of LN-144 for the treatment of metastatic melanoma at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting. This Phase 2, multicenter, three-cohort study is designed to assess the safety and efficacy of LN-144 for treatment of patients with metastatic melanoma. Cohorts one and two will now enroll up to 30 patients each and cohort three is a re-treatment cohort for a second LN-144 infusion in up to ten patients. The first two cohorts are evaluating two different manufacturing processes for LN-144. Patients in cohort one are receiving fresh, non-cryopreserved TIL and cohort two patients are receiving product manufactured through a more streamlined and rapid three-week procedure yielding a cryopreserved product. In the poster presentation entitled, "Efficacy of Single Administration of Tumor Infiltrating Lymphocytes (TIL) in Heavily Pre-treated Metastatic Melanoma Patients Following Checkpoint Therapy," Amod Sarnaik, MD, a surgical oncologist in the Department of Cutaneous Oncology at Moffitt Cancer Center and a member of the Immunology Program provided updated data from 16 patients in cohort one who were infused as of April 24, 2017. These advanced metastatic melanoma patients were a median age of 55 and were highly refractory to multiple prior lines of therapy with significant tumor burden at baseline. All had prior anti-PD-1 therapy, 88 percent had anti-CTLA4 therapy and 64 percent had received three or more prior therapies. The results show:
• – Of the evaluable patients, a 29 percent objective response rate was reported including one complete response (CR) continuing beyond 15 months post-administration of a single TIL treatment – 77 percent of patients had reduction in target tumor size Mean time to first response of 1.6 months, with the CR developing at 6 months – Responses were observed in patients with tumors carrying wild type or BRAF mutations
• The protocol allows for administration of up to 6 doses of IL-2. The median number of IL-2 administrations was six. Additionally, the protocol for this study was amended to both increase the sample size for the study as well as further define the patient population to patients with unresectable or metastatic melanoma who have progressed after immune checkpoint inhibition therapy (e.g., anti-PD-1), and if BRAF mutation-positive, after BRAF targeted therapy.
• • On May 19, 2017,Lion Biotechnologies announced that the first patient was dosed in the second cohort of its ongoing Phase 2 trial of LN-144 for the treatment of patients with metastatic melanoma. This cohort utilizes the company's generation 2 manufacturing process which includes cryopreservation of the outbound products. This process reduces the time from excision to infusion from approximately six weeks to just over three weeks.
• • On May 17, 2017, Lion Biotechnologies announced that new interim data from the first cohort of its ongoing Phase 2 study of LN-144 for the treatment of metastatic melanoma will be presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting. The data in the published abstract is from nine patients in cohort one who were infused as of January 31, 2017. These advanced metastatic melanoma patients are a median age of 56 and all had prior anti-PD1 as well as anti-CTLA4 therapy and 67 percent had received three or more prior therapies.
• • On September 14, 2015,  Lion Biotechnologies announced that it has opened enrollment in a Phase 2 clinical trial of LN-144, for the treatment of refractory metastatic melanoma. LN-144 is an autologous cell therapy of tumor-infiltrating lymphocytes (TIL) derived from the patient's own tumor and is based on TIL therapy regimens developed at the National Cancer Institute (NCI). Following a lymphocyte-depleting preparative regimen, patients are treated with a single infusion of LN-144 followed by IL-2.  The single-arm study is expected to enroll approximately 20 evaluable patients with metastatic melanoma whose disease has progressed following treatment with at least one systemic therapy. The trial will be conducted at up to five sites.In this study, patients will be evaluated for response 12 weeks after LN-144 infusion. Additionally, patients with stable disease and responders will be evaluated for progression-free survival (PFS), and overall survival (OS) for up to 24 months. Manufacturing for LN-144 will take place at a central cGMP manufacturing facility according to established protocols that are similar to those in use at NCI. The company expects to present initial trial data in 2016 in a scientific forum.

Is general: Yes