On July 7, 2025 Lutris Pharma, a clinical stage biopharmaceutical company focused on improving anti-cancer therapies by reducing cutaneous dose limiting toxicities, reported the presentation of results from its double-blind, placebo-controlled phase 2 randomized clinical trial of lead compound, LUT014 gel (Press release, Lutris Pharma, JUL 7, 2025, View Source [SID1234654268]). The topically-applied novel B-Raf inhibitor is optimized for paradoxical MAPK activation, for use by patients treated with epidermal growth factor receptor (EGFR) inhibitor therapy who develop dose-limiting acneiform rash. The clinical data was presented by Dr. Ofer Purim, Head of Gastrointestinal Malignancy Unit at the Helmsley Cancer Center, Shaare Zedek Medical Center, Jerusalem, Israel, in an oral presentation, entitled, "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," during a Proffered Paper Session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Gastrointestinal Cancers Congress 2025.
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"EGFR inhibitors, like cetuximab and panitumumab, are critical components of cancer therapy, but their effectiveness is often compromised by skin toxicities that can lead to dose modifications or treatment discontinuation," said Benjamin W. Corn, M.D., Chief Medical Officer of Lutris Pharma. "LUT014 is designed to mitigate these toxicities by restoring downstream signaling in skin cells disrupted by EGFR inhibition. In our clinical trial, the high dose of LUT014 demonstrated statistically significant efficacy in improving acneiform rash across both cetuximab and panitumumab-treated patients. Additionally, encouraging results were observed in the open-label extension, where even the low dose of LUT014 showed meaningful efficacy, with up to 69% of patients in the per-protocol population achieving improvement. LUT014 was also well tolerated, with fewer and mostly mild adverse events compared to placebo. We believe these results underscore LUT014’s potential to be a key therapeutic, offering significant benefits to patients by enabling them to remain on optimal anti-EGFR treatment without interruption."
"This is the first placebo-controlled, randomized trial to demonstrate both efficacy and safety of a treatment for anti-EGFR-induced acneiform rash, a major advancement in our effort to become the first company to provide a therapeutic that addresses the dose-limiting side effects of cancer treatments," added Sumant Ramchandra, M.D., Ph.D., Chief Executive Officer of Lutris Pharma. "Following its initial recognition at the AACR (Free AACR Whitepaper) Annual Meeting, the selection of our LUT014 data for oral presentation at the ESMO (Free ESMO Whitepaper) Gastrointestinal Cancers Congress further validates the clinical importance and growing momentum behind our lead program. Importantly, patients who respond best to EGFR inhibitor therapy are often the ones who experience the most severe cutaneous side effects, underscoring the urgent need for an effective solution in this underserved market. Our successful $30 million financing in January 2025 has enabled us to accelerate development of LUT014 and advance toward commercialization. Currently, there is no accepted standard of care or approved drugs for EGFR inhibitor associated cutaneous toxicity. We are hopeful that the ongoing development of LUT014 will be able to provide for this significant unmet medical need. As such, Lutris is well-positioned to help patients remain on life-saving cancer treatments, enhancing outcomes and dramatically improving quality of life."
The trial enrolled 118 colorectal cancer patients from 23 clinical sites, all of whom had developed grade 2 or non-infected grade 3 acneiform rash while receiving cetuximab or panitumumab. Participants were randomized in a 1:1:1 ratio to receive either LUT014 gel 0.03%, LUT014 gel 0.1%, or a placebo gel. The gel was applied daily for 28 days.
The primary endpoint was the proportion of patients who achieved treatment success, measured by an improvement of at least one grade in Common Terminology Criteria for Adverse Events (CTCAE) scoring or an improvement of at least 5 points in the Functional Assessment of Cancer Therapy (FACT)-EGFRI-18 HRQoL skin-specific assessment. The study employed both an intention-to-treat (ITT) analysis and a Per-Protocol (PP) analysis (i.e., patients who dropped out or did not discontinue their EGFR inhibitor for reasons unrelated to the rash, such as disease progression were excluded from the analysis). Sample size calculation was based on an expected treatment success of 20% for the placebo group and 50% for one of the treatment groups. A total of 117 patients were required for a two group ꭕ2 test with a 0.05 two-sided significance and 80% power.
Efficacy is shown in the table below. The high dose of LUT014 demonstrated statistically significant rates of success improving acneiform rash in both the cetuximab and panitumumab ITT groups, compared to placebo. Additionally, patients randomized to LUT014 gel had lower rates of interruption of cetuximab or panitumumab therapy due to acneiform rash.
N
Success Rate
P value
Panitumumab
High dose LUT014 (0.1%)
28
64.3 %
0.028
Low dose LUT014 (0.03%)
21
47.6 %
0.321
Placebo
27
33.3 %
Cetuximab
High dose LUT014 (0.1%)
11
81.8 %
0.021
Low dose LUT014 (0.03%)
19
47.4 %
0.448
Placebo
12
33.3 %
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 key pathways that regulate growth, survival, proliferation, and differentiation of cells. 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 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.
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 progressed on prior chemotherapy treatments. Although effective as anti-cancer therapy leading to tumor shrinkage, EGFR inhibitors have many 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 to the skin. When the B-Raf protein is mutated, as is the case in some human cancers such as melanoma, blocking this pathway leads to apoptosis of the cells and tumor shrinkage. However, when the same pathway is blocked in normal, non-mutated cells, the opposite happens: the MAPK pathway is activated, and cells start growing. This phenomenon is recognized as the paradoxical effect of B-Raf Inhibitors. LUT014 harnesses the paradoxical effect of B-Raf Inhibitors in order to enhance cell proliferation and balance cell destruction, typical to radiation dermatitis.