Lutris Pharma doses first US patients in phase 2 trial of LUT014 – a dose-limiting topical acneiform lesion reduction gel – in patients with metastatic colorectal cancer treated with an EGFR inhibitor
TEL AVIV, Israel, August 3, 2021 / PRNewswire / – Lutris Pharma, a clinical-stage biopharmaceutical company focused on improving cancer therapies by reducing dose-limiting side effects, today announced that the first U.S. patients have been assayed in the company’s Phase 2 trial of the lead compound, LUT014, a novel B-Raf inhibitor, for patients with metastatic colorectal cancer (mCRC) treated with an epidermal growth factor receptor inhibitor (EGFR) who have developed dose-limiting acneiform lesions. Recruitment and care of patients in Israel continues to progress. Based on the trial design, full and unblinded rolling 28-day results will be reported, if applicable.
The phase 2, randomized, double-blind, placebo-controlled trial is expected to enroll a total of 117 subjects at 20 sites, including 15 in the United States (including the 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 1: 1 randomization: 1), in mCRC patients who develop grade 2 EGFR inhibitor-induced acneiform lesions, with a follow-up period of 4 weeks. During an optional open-label extension period, for the placebo group, subjects will receive the 0.03% concentration of LUT014.
The primary endpoint of the study is the proportion of subjects in each treatment group who achieve treatment success, defined as an improvement (decrease) of at least one grade in the severity of the acneiform lesions of the line. based on day 28, based on common terminology criteria for adverse reactions Skin and Subcutaneous Tissue Disorders Rating Scale V5.0 (CTCAE) or improvement (increase) of at least 5 points in total score for skin-specific epidermal growth factor (the first 13 questions) of the Functional Assessment of Cancer Treatment Health-Related Quality of Life Questionnaire (HRQoL) of 18 Receptor Inhibitor (FACT-EGFRI-18) ), from inclusion to day 28. The main secondary endpoints include modification of the severity of acneiform lesions based on the CTCAE grading scale between inclusion and days 7, 14, 21, 28 e t 55; and change in FACT-EGFRI-18 total score for baseline skin-specific questions on days 7, 14, 21, 28, and 55.
“The assay of the first US patients is an important step in the progress of this international Phase 2 trial of LUT014,” said Noa Shelach, Ph.D., CEO of Lutris Pharma. “Although EGFR inhibitors are essential treatment options, over 80% of mCRC patients experience unwanted dermatologic side effects, including a papulopustular rash – also known as acneiform lesions – which reduces their quality of life and, more importantly, may lead to reduction or discontinuation of treatment. By reversing the inhibitory effect of EGFR inhibitors on downstream proteins in skin cells, we believe that LUT014 has the potential to become an important addition to treatment regimens and may have a huge impact on patients who do not. ‘currently have no other treatment options. ”
Mario E. Lacouture, MD, director of the oncodermatology program at Memorial Sloan Kettering Cancer Center, noted, “The development of acneiform rash caused by EGFR inhibitors, including cetuximab, panitumumab and others, may affect the quality of life and consistency of dosage, and in the absence of any treatments, there is an unmet need for approved topical therapies. Lutris phase 1 results in mCRC patients were promising, with no dose-limiting toxicity and therapeutic benefit in all patients. As a result, we look forward to participating in the Phase 2 trial and interim results later this year. ”
For more information about this clinical trial, please visit: www.clinicaltrials.gov, NCT04759664.
Dr Lacouture provided consultation and advisory services to Lutris Pharma.
About rash induced by EGFR inhibitors
EGFR is a cell surface receptor that is expressed in many normal epithelial tissues, including the skin. The EGFR signaling pathway is one of the most important pathways that regulate cell growth, survival, proliferation, and differentiation. B-Raf is a protein encoded by the BRAF gene and is a downstream effector component of the EGFR signaling pathway. EGFR has been shown to be overactivated in a variety of human cancers, including colorectal, lung, head and neck, bladder, pancreas and breast cancers, causing downstream phosphorylation and activation of the MAP Kinase pathway.
Medicines called EGFR inhibitors can block the EGFR signal responsible for cell growth. Among the different types of pharmacological therapies for cancer, EGFR inhibitors are increasingly used both as primary therapy as well as in patients who have failed previous chemotherapy. Although effective as an anticancer therapy leading to tumor shrinkage, EGFR inhibitors have a number of adverse effects associated with their use. The majority of patients treated with EGFR inhibitors will experience unwanted dermatologic side effects usually manifesting as a papulopustular rash, also known as acneiform lesions, which can impact quality of life and longevity. adherence to treatment.
LUT014 is a new inhibitor of B-Raf which is applied topically to the skin. The B-Raf protein is part of the EGFR pathway and has been shown to be mutated in certain human cancers such as melanoma cancer. Blocking the B-Raf pathway in B-Raf mutated cancer cells results in tumor shrinkage, but when the same pathway is blocked in normal, unmutated cells, the opposite happens: the MAP Kinase pathway is activated and cells start to grow. This phenomenon is recognized as the paradoxical effect of B-Raf inhibitors. LUT014 exploits this paradoxical effect to reverse the effect of EGFR inhibitors on downstream proteins in skin cells, thereby reducing the dose-limiting acneiform lesions associated with EGFR inhibitor treatment.
About Lutris Pharma
Lutris Pharma is a clinical-stage biopharmaceutical company focused on improving the efficacy of anticancer therapies and the quality of life of patients treated with EGFR (Epidermal Growth Factor Receptor) inhibitors or radiotherapy, where toxicity skin often leads to a reduction in anti-adherence to cancer treatment. The company aims to provide new topical therapies to alleviate these side effects. Lutris Pharma’s main active ingredient, LUT014, a topical B-Raf inhibitor, is a proprietary, first-in-class small molecule, currently in a Phase 2 clinical trial in patients with metastatic colorectal cancer with induced acneiform lesions. by an EGFR inhibitor and a phase 1/2 study for the treatment of radiation-induced dermatitis in patients with breast cancer. For more information, please visit www.lutris-pharma.com.
Noa Shelach, Ph.D. Chief
Rx communication group
SOURCE Lutris Pharma