Lutris Pharma Phase 1 Results of LUT014 for Skin Toxicities Associated with Treatment of Colorectal Cancer Patients with EGFR Inhibitors Published in Cancer Discovery

LUT014 was found to be safe and effective

LUT014 Phase 2 trial designed to include 117 patients in 20 centers in the US and Israel has been initiated

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Apr 28, 2021, 10:11 ET

TEL AVIV, Israel, April 28, 2021 /PRNewswire/ -- Lutris Pharma, a clinical stage biopharmaceutical company focusing on improving anti-cancer therapies by reducing dose limiting side effects, announced today that results of a Phase1 study for its lead product, LUT014, assessing the safety, tolerability, and efficacy of topically administered LUT014 for the treatment of epidermal growth factor receptor (EGFR) inhibitor-induced acneiform lesions in metastatic colorectal cancer patients, were published in Cancer Discovery a journal of the American Association for Cancer Research.

EGFR inhibitors, such as the anti-EGFR monoclonal antibodies cetuximab or panitumumab, are valuable therapeutic options in metastatic colorectal cancer. However, their use is often associated with skin toxicities, leading to potentially severe acne-like rashes on the face, chest and back, resulting in a reduced quality of life as well as treatment discontinuation. In fact, 70-80% of patients treated with EGFR inhibitors who developed a rash do not receive optimal anti-cancer treatment.[i]

LUT014 is a topical drug designed to ameliorate the skin toxicity of EGFR inhibitors. The Phase 1 clinical trial for assessing the safety, tolerability and initial efficacy of LUT014 was conducted in four leading centers in the US and two in Israel[ii], on 10 patients with metastatic colorectal cancer who had developed a grade 1 or 2 acneiform rash while being treated with cetuximab or panitumumab. Patients were divided into three dose cohorts, of 0.3, 1 or 2.5 mg/g and were treated for 28 days. In all dosage levels, LUT014 was well tolerated with no dose limiting toxicities. The acneiform rash improved in all the patients who started with grade 2 rash in the low and intermediate dose cohorts (6 patients), and the improvement was maintained a month after treatment cessation.

In light of the positive results, Lutris initiated a Phase 2, randomized, double-blind, placebo-controlled efficacy and safety study of topically administered LUT014 in metastatic colorectal cancer patients with EGFR inhibitor-induced acneiform lesions. The study is designed to include 117 patients in 20 centers in the US and Israel, who will be treated for 28 days with either LUT014 gel or a placebo. The primary outcome is the proportion of subjects in each treatment group who reached treatment success, defined as an improvement (decrease) of at least one grade in the severity of the acneiform lesions from baseline to day 28. Interim results are expected by the end of 2021.

Antoni Ribas, M.D., Ph.D., Professor of Medicine, Surgery, and Molecular and Medical Pharmacology at the University of California Los Angeles, contributing author, and founder and director at Lutris Pharma, said, "We are excited with the positive results and high response rate seen in this preliminary trial for LUT014 in treating skin toxicities of EGFR inhibitors. These promising results offer initial hope that the potential of EGFR inhibitors, a significant tool for the treatment of metastatic colorectal cancer, could be maximized with fewer adverse effects."

Lead author Mario E. Lacouture, MD, Director of the Oncodermatology Program at Memorial Sloan Kettering Cancer Center in New York City, noted, "EGFR is highly expressed in skin cells, and therefore inhibition of this pathway in patients with cancer often results in debilitating skin rash that is frequently pruritic or painful, and may decrease quality of life and cancer therapy dosing. The preliminary results of the Phase 1 trial are encouraging, and future trials have the potential to translate this therapy into a clinically available treatment option for patients experiencing these untoward events from cancer treatment."

Noa Shelach, PhD, MBS, CEO of Lutris Pharma, said, "Currently there is no approved therapy for acneiform rash that accompany EGFR inhibition in up to 90% of patients. Most of the patients are not optimally treated for their cancer and their quality of life is negatively affected. LUT014 is emerging as an extremely useful topical treatment for EGFR-related acneiform rash, with no systemic adverse effects. In fact, our analysis shows there is negligible absorption and minimal systemic exposure to the drug. While this clinical trial assessed the effect of LUT014 on inhibition of EGFR by therapeutic antibodies, it is also applicable to acneiform rash induced by EGFR inhibitors that are small molecules. We look forward to the interim results of our ongoing Phase 2 trial with LUT014 for treating skin toxicities of EGFR inhibition, expected by the end of the year."

About LUT014

LUT014 is a novel B-Raf inhibitor which is applied topically on the skin. The B-Raf protein is part of the EGFR pathway, and was shown to be mutated in some human cancers such as melanoma cancer. Blocking the B-Raf pathway in B-Raf mutated cancer cells leads to tumor shrinkage, but when the same pathway is blocked in normal, non-mutated cells, the opposite happens: the MAPK pathway is activated and cells start growing. This phenomenon is recognized as the paradoxical effect of B-Raf Inhibitors. LUT014 harnesses the paradoxical effect of B-Raf Inhibitors in order to reverse the effect of EGFR inhibitors on downstream proteins in the skin cells, thereby reducing dose-limiting acneiform lesions associated with EGFR inhibitor treatment. Lutris Pharma is currently assessing the effectiveness of LUT014 in two clinical studies: a Phase 2 study for reduction of dose-limiting acneiform lesions associated with EGFRI treatment of metastatic colorectal cancer, and a Phase 1/2 study for the treatment of radiation induced dermatitis in breast cancer patients.

About EGFR inhibitor-induced rash

EGFR (Epidermal Growth Factor Receptor) is a receptor on the surface of cells which is expressed in many normal epithelial tissues, including skin. The EGFR signaling pathway is one of the most important pathways that regulate growth, survival, proliferation, and differentiation of cells. B-Raf is protein encoded by the BRAF gene and is a downstream effector component of EGFR signaling pathway. EGFR is shown to be over-activated in various human cancers, including colorectal, lung, head & neck, urinary bladder, pancreatic and breast cancers. While over-activated, it elicits downstream phosphorylation and activation of the MAP Kinase pathway.

Drugs called EGFR inhibitors can block the EGFR signal responsible for cell growth. Among the various types of pharmacological therapies for cancer, EGFR inhibitors are increasingly being used both as primary therapy as well as in patients who have failed prior chemotherapy. Although effective as anti-cancer therapy leading to tumor shrinkage, EGFR inhibitors have a number of adverse reactions associated with their use. The majority of patients treated with EGFR inhibitors will experience dermatological side effects typically manifested as a papulopustular skin rash, also known as acneiform lesions, which can impact quality of life and affect adherence to therapy.

About Lutris Pharma

Lutris-Pharma was established with a vision of improving anti-cancer therapy effectiveness as well as the quality of life for patients that are treated with EGFR (Epidermal Growth Factor Receptor) inhibitors or with radiation. Dermal toxicity is the most prominent adverse reaction of EGFR Inhibitor therapy and radiation therapy, thus limiting anti-cancer therapy compliance. By mitigating this side effect, Lutris Pharma enables continuous and effective EGFR Inhibitors and radiation treatment. Investors in the Company include Pontifax Venture Capital, Arkin Holdings and Catalyst Investments.

Dr. Lacouture has provided consulting and advisory services to Lutris Pharma.

Media Contacts:
Tsipi Haitovsky, Global Media Liaison, Lutris Pharma
+972-52-598-9892, [email protected]

[i] Support Care Cancer (Lacouture et al. 2011)

[ii] University of Texas MD Anderson Cancer Center, Houston, TX
Memorial Sloan Kettering Cancer Center, New York, NY
University of California, Los Angeles, Hematology and Oncology, Santa Monica, CA
Washington University School of Medicine, St. Louis, MO
Rabin Medical Center, Petach Tikva, Israel
Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel