Compared with a placebo gel, an investigational topical BRAF inhibitor (LUT014) was found to improve the symptoms of acneiform rash in patients with colorectal cancer. These phase II clinical trial results were presented by Anisha B. Patel, MD, Associate Professor of Dermatology, Deputy Chair of Research in Dermatology, and Section Chief of Cutaneous Toxicities at The University of Texas MD Anderson Cancer Center, at the 2025 American Association for Cancer Research (AACR) Annual Meeting (Abstract CT018).
EGFR-targeted drugs are approved to treat colorectal and other cancers, but up to 75% of patients receiving these therapeutics experience acneiform rash, noted Dr. Patel. “Acneiform rash often leads to delays, dose reduction, or discontinuation of EGFR-targeted cancer therapies,” she said. “Better control of acneiform rash could, therefore, improve treatment continuation and lead to better control of the patient’s cancer.”
When a patient receives a systemic EGFR-targeted therapeutic, it blocks EGFR activity and downstream signaling in multiple organs, including the skin—where the subsequent dysregulation of skin cells induces inflammatory responses that lead to the rash, Dr. Patel explained. Inhibition of the BRAF protein is known to paradoxically reactivate signaling downstream of EGFR, she added. Thus, she and her colleagues reasoned that inhibiting BRAF locally at sites of acneiform rash might reverse the effects of EGFR inhibition in the skin and reduce the severity of the rash.
Study Details and Key Findings
To test this hypothesis, the researchers conducted a multicenter phase II clinical trial to evaluate the efficacy of LUT014 gel in 118 patients with colorectal cancer who developed grade 2 or 3 acneiform rash while receiving an EGFR-targeted antibody (such as cetuximab or panitumumab).
Enrolled patients were randomly assigned to receive a 0.03% formulation of LUT014 gel, a 0.1% formulation of LUT014 gel, or a placebo gel. Patients applied the gel to the rash each day for 28 days. Treatment success was defined as a one-grade or greater reduction in rash severity and/or improvement in at least five skin-specific, health-related quality-of-life criteria by the end of the 28-day period.
Compared with the patients in the placebo arm, those who received the 0.1% LUT014 formulation were significantly more likely to experience treatment success (33% success rate for the placebo arm vs 69% for the 0.1% LUT014 arm). For those who received the 0.03% LUT014 formulation, the treatment success rate was 47.5%, which was numerically higher but not statistically different from placebo.
Treatment-related adverse events included itchiness, burning sensation, skin redness, and stinging at the application site for patients treated with LUT014. Patients treated with the placebo gel experienced similar adverse events. Most of the adverse events in patients who received the LUT014 gel were grade 1, with one patient given 0.1% LUT014 and three patients given placebo experiencing grade 3 adverse events.
“LUT014 gel improved acneiform rash in the majority of treated patients within a remarkably short time frame of 28 days,” stated Dr. Patel. “This investigational topical BRAF inhibitor has the potential to not only improve quality of life for patients receiving EGFR-targeted therapy but also improve their cancer treatment compliance and potentially their tumor response.” LUT014 gel will next be evaluated in a phase III clinical trial.
Although LUT014 led to skin reactions similar to the symptoms of acneiform rash, Dr. Patel explained that the adverse events were consistent with those typically seen when applying a topical agent to inflamed skin and were an improvement over the symptoms of the rash itself. “Our metric for treatment success is a composite outcome that includes clinically significant improvement in quality of life, so even though patients had adverse events with symptoms overlapping with those of acneiform rash, their overall quality of life improved,” she added.
A limitation of the study was that it enrolled only patients with colorectal cancer treated with EGFR-targeted antibodies, which precludes understanding how the treatment might benefit patients with other cancer types or patients treated with kinase inhibitors of EGFR. Another limitation was the short follow-up, which did not allow for sufficient assessment of how LUT014 impacted compliance with EGFR-targeted therapy. Although exploratory analyses suggested LUT014 may have increased adherence to EGFR-targeted therapy, Dr. Patel cautioned that the study was not designed to evaluate adherence.
Disclosure: The study was funded by Lutris Pharma. Dr. Patel has served on an advisory board for Novartis; has received consulting fees from Asymmetric Therapeutics, Deciphera Pharmaceuticals, Erasca, Janssen Scientific Affairs, Lutris Pharma, OnQuality Pharmaceuticals, Repare Therapeutics, and SynOx Therapeutics; and has received institutional research funding from AnaptysBio, Hoth Therapeutics, Lutris Pharma, OnQuality Pharmaceuticals, and Pfizer. For full disclosures of the other study authors, visit abstractsonline.com.
