On August 3, 2021 Lutris Pharma, a clinical stage biopharmaceutical company focused on improving anti-cancer therapies by reducing dose limiting side effects, reported that the first U.S. patients have been dosed as part of the Company’s phase 2 trial of lead compound, LUT014, a topically applied, novel B-Raf inhibitor, for metastatic colorectal cancer patients (mCRC) being treated with epidermal growth factor receptor (EGFR) inhibitor therapy who have developed dose-limiting acneiform lesions (Press release, Lutris Pharma, AUG 3, 2021, View Source;-a-topical-gel-for-the-reduction-of-dose-limiting-acneiform-lesions—-in-metastatic-colorectal-cancer-patients-treated-with-egfr-inhibitor-therapy-301346759.html [SID1234585652]). Recruitment and treatment of patients in Israel continues to progress. Based on the trial design, full, unblinded 28-day rolling results will be reported, as appropriate.

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The phase 2, randomized, double-blind, placebo-controlled trial is expected to enroll a total of 117 subjects at 20 sites, consisting of 15 in the U.S. (including Memorial Sloan Kettering Cancer Center in New York) and five in Israel. The trial will evaluate the efficacy and safety of two strengths of LUT014 Gel, 0.03% or 0.10%, applied once daily for 4 weeks, compared to placebo (with a randomization of 1:1:1), in patients with mCRC who develop Grade 2 EGFR inhibitor-induced acneiform lesions, with a 4-week follow up period. During an optional open label extension period, for the placebo group, subjects will receive the 0.03% concentration of LUT014.

The study’s primary endpoint is the proportion of subjects in each treatment group who reach treatment success, defined as an improvement (decrease) of at least one grade in the severity of the acneiform lesions from baseline to Day 28, based on common terminology criteria for adverse events (CTCAE) V5.0 skin and subcutaneous tissue disorders grading scale or, an improvement (increase) of at least 5 points in the total score for the skin-specific (first 13 questions) of the functional assessment of cancer therapy epidermal growth factor receptor inhibitor 18 (FACT-EGFRI-18) health related quality of life (HRQoL) questionnaire, from baseline to Day 28. Key secondary endpoints include change in the severity of acneiform lesions based on CTCAE grading scale from baseline to Days 7, 14, 21, 28, and 55; and change in the FACT-EGFRI-18 questionnaire total score for the skin-specific questions from baseline to Days 7, 14, 21, 28, and 55.

"Dosing of the first U.S. patients is a significant milestone in the progression of this international, phase 2 trial of LUT014," stated Noa Shelach, Ph.D., Chief Executive Officer of Lutris Pharma. "While EGFR inhibitors are critical treatment options, over 80% of mCRC patients experience adverse dermatological side effects, including papulopustular skin rash – also known as acneiform lesions – which reduces their quality of life, and more importantly, may lead to a reduction or discontinuation of treatment. By reversing the inhibitory effect of EGFR inhibitors on downstream proteins in the skin cells, we believe that LUT014 has the potential to become an important addition to therapeutic regimens and can have a tremendous impact for patients who currently have no other treatment options."

Mario E. Lacouture, M.D., Director of the Oncodermatology Program at Memorial Sloan Kettering Cancer Center, noted, "Development of the acneiform rash caused by EGFR inhibitors including cetuximab, panitumumab and others, may affect quality of life and consistent dosing, and in the absence of any approved treatments, there is an unmet need for approved topical therapies. Lutris’ phase 1 results in patients with mCRC were promising, with no dose limiting toxicities and a therapeutic benefit in all patients. As a result, we look forward to participating in the phase 2 trial and to the interim results later this year."

For more information on this clinical trial, please visit: www.clinicaltrials.gov, NCT04759664.

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

About EGFR inhibitor-induced rash
EGFR 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 and neck, urinary bladder, pancreatic and breast cancers, eliciting 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 adverse 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 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 has 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 MAP Kinase pathway is activated and cells start growing. This phenomenon is recognized as the paradoxical effect of B-Raf Inhibitors. LUT014 harnesses this paradoxical effect 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.