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The first participants from the United States have been dosed with LUT014, a novel, topical BRAF inhibitor in a phase 2 trial that is evaluating the agent in patients with metastatic colorectal cancer who have developed dose-limiting acneiform lesions following treatment with an EGFR inhibitor.
The first participants from the United States have been dosed with LUT014, a novel, topical BRAF inhibitor in a phase 2 trial (NCT04759664) that is evaluating the agent in patients with metastatic colorectal cancer (mCRC) who have developed dose-limiting acneiform lesions following treatment with an EGFR inhibitor, according to a news release from Lutris Pharma, the developer of the agent.1
The investigators will continue to recruit and treat patients in Israel, and full unblinded 28-day rolling results will be released in accordance with the trial design, when ready.
“Development of the acneiform rash caused by EGFR inhibitors, including cetuximab [Erbitux], panitumumab [Vectibix] 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,” said Mario E. Lacouture, MD, director of the Oncodermatology Program at Memorial Sloan Kettering Cancer Center.
LUT014 is a proprietary, first-in-class, small molecule that reverses the effects of EGFR inhibitors on downstream proteins in skin cells, reducing dose-limiting acneiform lesions associated with EGFR inhibitor treatment.
The agent demonstrated “promising” findings, with no dose-limiting toxicities and a clinical benefit in prior findings from the phase 1 trial (NCT03876106) in patients with mCRC.
The ongoing, phase 2, randomized, double-blind, placebo-controlled trial has an expected enrollment of 117 patients across 20 sites, consisting of 15 in the United States, and 5 in Israel.
The 5 sites in the United States include Memorial Sloan Kettering Cancer Center, University of California Los Angeles, Dana-Farber Cancer Institute, University of Tennessee, and The University of Texas MD Anderson Cancer Center.
To be eligible for enrollment, patients must have mCRC with grade 2 EGFR inhibitor–induced acneiform lesions.
“While EGFR inhibitors are critical treatment options, over 80% of mCRC patients experience adverse dermatological [adverse 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,” said Noa Shelach, PhD, chief executive officer of Lutris Pharma.
Patients will be randomized 1:1:1 to 1 of 2 strengths of LUT014 gel: 0.03% or 0.10%, applied once daily for 4 weeks or placebo, with 4 weeks of follow-up. During an optional open-label extension period, patients randomized to the placebo arm will receive the 0.03% concentration of LUT014.
The primary end point of the study is the proportion of patients in each treatment arm who achieve treatment success, defined as a reduction of at least 1 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 a rise of at least 5 points in the total score for the first 13, skin-specific 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 end points include the change in the severity of acneiform lesions based on CTCAE grading scale from baseline to days 7, 14, 21, 28, and 55; and the 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 United States patients is a significant milestone in the progression of this international, phase 2 trial of LUT014,” said Shelach.
LUT014 is also being evaluated in a phase 1/2 study (NCT04261387) for the treatment of radiation-induced dermatitis in patients with breast cancer.