Abstract OT1-06-01: Lymfactin, an investigational adenoviral gene therapy expressing VEGF-C, is currently studied in a double-blind, randomized, placebo-controlled, multicenter, phase 2 clinical study in patients suffering from breast cancer associated secondary lymphedema (BCAL)

Abstract

Abstract Background: Over 15,000 new breast cancer associated secondary lymphedema (BCAL) cases are diagnosed annually in the US. For advanced stage secondary lymphedema, the only current treatment options include conservative therapy and surgical interventions. There is no curative treatment available. Lymfactin is a novel adenovirus type 5-based gene therapy expressing human growth factor VEGF-C, which is highly specific for lymphangiogenesis. Lymfactin is administered directly in the tissue with the compromised lymph flow. By promoting the growth of lymphatic vessels, the aim is to restore a functional lymphatic network and flow. In a previous first in human Phase 1 clinical study in 15 patients, a single dose of Lymfactin was administered as an adjunct to lymph node transplantation surgery in BCAL patients. Lymfactin was safe and well tolerated, and no dose limiting toxicities were observed. Data at 12 months showed that the volume difference of the affected arm compared to the normal arm decreased >50% in at least half of the patient population. Improvements in the function of the lymphatic system were also observed by quantitative lymphoscintigraphy and quality of life. We are now investigating the efficacy of Lymfactin in a randomized clinical setting. Trial design: We are currently conducting a double-blind, randomized, placebo-controlled, Phase 2 clinical study with Lymfactin in BCAL patients. This multi-center study is enrolling patients in Finland and in Sweden scheduled for lymph node transplantation surgery. In this study a single dose of Lymfactin or placebo (saline) is administered ex vivo in the lymph node transplant during the surgery. A total of 40 patients will be randomized 1:1 to this study. Main eligibility criteria: 1. Female or male patients with secondary lymphedema associated with the treatment of breast cancer and a. Has undergone sentinel lymph node biopsies and/or lymph node resection in the axilla on the affected side of their breast cancer with initial N1-N2a staging and lymph node metastasis in ≤ 9 axillary lymph nodes. b. Requires garment use as a compression treatment for the lymphedema in the affected arm. c. Has the volume of the affected arm at least 10% greater than the unaffected arm following 7 days without a compression garment. d. Has the presence of pitting edema in the affected arm without compression garment. e. Has had lymphedema for less than 5 years. 2. No evidence of recurrent or active breast cancer for at least 2 years after the breast cancer surgery and/or the end of chemotherapy and/or radiotherapy (excluding endocrine treatment). Specific Aims: Evaluation of the effects of the Lymfactin treatment on the signs and symptoms of lymphedema by comparing the effects of the active study treatment Lymfactin to corresponding placebo up to 24 months post-treatment by measuring the change in the volume of the affected arm, quantitative lymphoscintigraphy, and patient lympedema specific quality of life assessment. Statistical methods: All efficacy analyses will be performed on the intent-to-treat and per protocol analysis sets. The efficacy data parameters will be summarized using descriptive statistics by treatment group and time point, as appropriate. Due to the nature of the study, there are no set formal statistical hypotheses for the efficacy endpoints, but suitable inferential statistics can be used when feasible. Present accrual and target accrual: A total of 40 patients are planned to be included in the clinical study. By the end of June 2019, 15 patients have been enrolled. Contact: Outi Lahdenperä, MD CMO Herantis Pharma Plc E-mail: outi.lahdenpera@herantis.com Tel: +358 40 511 3194 Citation Format: Pauliina Hartiala, Outi Lahdenperä, Antti Vuolanto, Anne Saarikko. Lymfactin, an investigational adenoviral gene therapy expressing VEGF-C, is currently studied in a double-blind, randomized, placebo-controlled, multicenter, phase 2 clinical study in patients suffering from breast cancer associated secondary lymphedema (BCAL) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-06-01.