LUT014 Gel Demonstrates Efficacy in Treating Acneiform Rash Associated with Use of Anti-EGFR Cancer Therapies

Patients with colorectal cancer who had acneiform rash and applied LUT014 gel (Lutris Pharma), an investigational topical BRAF inhibitor designed to reduce cutaneous dose limiting toxicity, were more likely to experience improvement of their rash compared with patients who used a placebo gel.[1]

This is the conclusion based on result of a recently completed, double-blind, placebo-controlled phase 2 randomized clinical trial presented at the annual meeting of the American Association for Cancer Research (AACR), held April 25-30, 2025 in Chicago, Illinois.

The  study outcomes demonstrate statistically-significant reductions in dose-limiting acneiform rash in patients treated with epidermal growth factor receptor (EGFR) inhibitor therapy. This new clinical data, showing that LUT014 topically-applied novel B-Raf inhibitor gel is optimized for paradoxical mitogen-activated protein kinase (MAPK) pathway activation.[1]

“Epidermal growth factor receptor (EGFR)-targeted drugs are approved to treat colorectal and other cancers, but up to 75% of patients receiving these therapeutics experience acneiform rash, an often painful and itchy skin toxicity,” according to Anisha B. Patel, MD, an 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.

“Acneiform rash often leads to delays, dose reduction, or discontinuation of EGFR-targeted cancer therapies,” Patel said.

“Better control of acneiform rash could, therefore, improve treatment continuation and lead to better control of the patient’s cancer,” she added.

Inflammatory response
“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,” Patel explained.

“Inhibition of the BRAF protein is known to paradoxically reactivate signaling downstream of EGFR,” Patel added.

Together with her colleagues, she 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.

To test this hypothesis, the researchers conducted a multicenter phase 2 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 (Erbitux®; Eli Lilly and Company) or panitumumab (Vectibix®; Amgen).

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, and 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 (hrQoL) criteria by the end of the 28-day period.

Treatment success
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, including burning sensation, skin irritation, and stinging at the application site. Most of the adverse events in patients who received the LUT014 gel were grade 1, with one patient in the 0.1% LUT014 arm and three in the placebo arm 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,” noted 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.”

Patel added that LUT014 gel will next be evaluated in a phase 3 clinical trial.

Skin reactions
While LUT014 led to skin reactions similar to the symptoms of acneiform rash, 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 said.

Study limitation
A limitation of the study was that it only enrolled 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 time, which did not allow for sufficient assessment of how LUT014 impacted compliance with EGFR-targeted therapy. While exploratory analyses suggested that LUT014 may have increased adherence to EGFR-targeted therapy, Patel cautioned that the study was not designed to evaluate adherence.

The study was funded by Lutris Pharma.

Clinical trials
LUT014 for the Treatment of Radiation Induced Dermatitis in Breast Cancer Patients – ClinicalTrials.gov ID NCT04261387
LUT014 for the Reduction of Dose-Limiting Acneiform Lesions Associated With EGFRI Treatment of mCRC – ClinicalTrials.gov ID NCT04759664

Highlights of prescribing information
Cetuximab (Erbitux®; Eli Lilly and Company)[Prescribing Information]
Panitumumab (Vectibix®; Amgen)[Prescribing Information]

Reference
[1] Patel AB, Purim O, Wainberg ZA, LeBoeuf N, Imanirad I, Dotan E, Khoury J, Rotemberg V, Zuniga R, Marballi A, Tahover E, Veluvolu A, Bailey S, Greenberg D, Akhtar A, Shelach N, Corn BW, Ribas A, Lacouture ME. A double-blind placebo-controlled randomized phase 2 clinical trial to assess the efficacy of a topical BRAF inhibitor for acneiform rash toxicities from anti-EGFR therapies. In: Proceedings of the 116th Annual Meeting of the American Association for Cancer Research; 2025 April 25-30; Chicago, IL.: AACR; 2025. Abstract nr CT018.

Featured image: Millenium Park, Chicago, Illinois. Photo licensed under the Unsplash+ License

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