LUT014 / Lutris Pharma - LARVOL DELTA

Lutris Pharma Presents Additional Positive Data from Its Phase 2 Trial of LUT014 Gel Demonstrating Significant Efficacy in Treating Acneiform Rash Associated with Use of Anti-EGFR Cancer Therapies at the ESMO Gastrointestinal Cancers Congress 2025 (PRNewswire) - P2 | N=117 | NCT04759664 | Sponsor: Lutris Pharma Ltd. | "Lutris Pharma...announced the presentation of results from its double-blind, placebo-controlled phase 2 randomized clinical trial of lead compound, LUT014 gel...'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.'....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."

P2 data • Dermatitis

Lutris Pharma Presents New Data from Its Completed Clinical Trial of LUT014 Gel Demonstrating Efficacy in Treating Acneiform Rash Associated with Use of Anti-EGFR Cancer Therapies at AACR Annual Meeting 2025 (PRNewswire) - P2 | N=357 | NCT04759664 | Sponsor: Lutris Pharma Ltd. | "Lutris Pharma...presented data from its recently completed double-blind, placebo-controlled phase 2 randomized clinical trial of lead therapy, LUT014 gel, demonstrating statistically-significant reductions in dose-limiting acneiform rash in patients treated with epidermal growth factor receptor (EGFR) inhibitor therapy....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....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."

P2 data • Dermatitis

Lutris Pharma to Present at the American Association for Cancer Research Annual Meeting 2025 (PRNewswire) - "Lutris Pharma...today announced the upcoming presentation of the results of its double-blind, placebo-controlled phase 2 randomized clinical trial of lead compound, LUT014 gel....The new clinical data will be released in an oral presentation at the Clinical Trials Plenary Session at the American Association for Cancer Research (AACR) Annual Meeting 2025, being held April 25-30 in Chicago, IL."

P2 data • Dermatitis

Lutris Pharma Completes Enrollment in Phase 2 Trial of LUT014 for the Treatment of EGFRI-Induced Acneiform Rash in Patients with Metastatic Colorectal Cancer (PRNewswire) - "Lutris Pharma...announced that it has completed enrollment in the phase 2 trial of lead compound, LUT014...for patients with metastatic colorectal cancer (mCRC) treated with epidermal growth factor receptor (EGFR) inhibitor therapy who develop dose-limiting acneiform rash. Topline results are expected in first quarter of 2025....The phase 2, randomized, double-blind, placebo-controlled trial has enrolled a total of 117 subjects at 20 international sites, including Memorial Sloan Kettering Cancer Center, MD Anderson Cancer Center and Dana Farber Cancer Institute. The trial is evaluating 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 randomization of 1:1:1), in patients with mCRC who develop Grade 2 or non-infected Grade 3 EGFR inhibitor-induced acneiform rash, with a 4-week follow up period. During an optional open label extension period for the placebo group, eligible subjects received..."

Enrollment closed • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Lutris Pharma Receives FDA Orphan Drug Designation for LUT014 for the Treatment of EGFRI-Induced Acneiform Rash (PRNewswire) - "Lutris Pharma...announced that the U.S. Food and Drug Administration's (FDA) Office of Orphan Products Development has granted Orphan Drug Designation (ODD) to lead compound, LUT014, a novel topically applied B-Raf inhibitor, for the treatment of EGFR (Epidermal Growth Factor Receptor) inhibitor induced acneiform rash. Currently, no drug or treatment is approved by the FDA for the prevention or treatment of EGFR inhibitor induced acneiform lesions."

Orphan drug • Immunology • Inflammation

A topical BRAF inhibitor (LUT-014) for treatment of radiodermatitis among women with breast cancer. (PubMed, JAAD Int) - "Only 2 hospitals were included. Topical LU014 is tolerable and may be efficacious for grade 2 RD."

Journal • Breast Cancer • Dermatitis • Dermatology • Immunology • Oncology • Solid Tumor

Lutris Pharma Announces Publication of Positive Data From Its Phase 1/2 Trial of LUT014 to Treat Radiation Dermatitis in Patients with Breast Cancer (PRNewswire) - P1/2 | N=28 | NCT04261387 | Sponsor: Lutris Pharma Ltd. | "Lutris Pharma...announced the publication of data from its phase 1/2 trial of lead compound, LUT014, a topically applied, novel B-Raf inhibitor, for the treatment of radiation-induced dermatitis (RD) in patients with breast cancer....Part 1 results showed that, of the eight enrolled patients who developed grade 2 RD at baseline, 75% (6/8) had complete resolution, improving to grade 0 dermatitis, and 100% of patients had RD of 1 or 0 as assessed by the Common Terminology Criteria for Adverse Events (CTAE) after 28 days of daily, topically applied LUT014 gel....Overall, four out of eight (50%) subjects had recovered completely in the LUT014 Gel group while four out of 11 (36%) subjects had recovered completely in the placebo group by the end of the study (Day 28) (p=0.6577). None of these differences reached conventional levels of statistical significance, however, this small study was not powered to show such differences."

P1/2 data • Breast Cancer • Oncology • Solid Tumor

LUT014 for the Reduction of Dose-Limiting Acneiform Lesions Associated With EGFRI Treatment of mCRC (clinicaltrials.gov) - P2 | N=117 | Recruiting | Sponsor: Lutris Pharma Ltd. | Trial completion date: Sep 2023 ➔ May 2024 | Trial primary completion date: Jun 2023 ➔ Mar 2024

Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Lutris Pharma Reports Positive Top-Line Results From the Open Label Part 1 and Double Blinded Part 2 of Its Phase 1/2 Trial of LUT014 to Treat Radiation Dermatitis in Patients with Breast Cancer (PRNewswire) - "Antoni Ribas, M.D...noted, 'These favorable results in patients with radiation dermatitis, coupled with the highly encouraging data generated, thus far, in the company's study of LUT014 in patients with mCRC with EGFR inhibitor induced acneiform lesions, tells us that the LUT014 compound is active to treat skin conditions that could benefit from the topical administration of this small molecule BRAF inhibitor, which opens the door to its use in numerous additional indications, and we look forward to exploring these options and expanding the pipeline in the future.'"

Media quote

LUT014 for the Reduction of Dose-Limiting Acneiform Lesions Associated With EGFRI Treatment of mCRC (clinicaltrials.gov) - P2 | N=117 | Recruiting | Sponsor: Lutris Pharma Ltd. | Trial completion date: Jun 2023 ➔ Sep 2023 | Trial primary completion date: Mar 2023 ➔ Jun 2023

Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Lutris Pharma Reports Positive Top-Line Results From the Open Label Part 1 and Double Blinded Part 2 of Its Phase 1/2 Trial of LUT014 to Treat Radiation Dermatitis in Patients with Breast Cancer (PRNewswire) - P1/2 | N=28 | NCT04261387 | Sponsor: Lutris Pharma Ltd. | "Lutris Pharma...announced positive top-line results from the open label part 1 and double blinded part 2 of its phase 1/2 trial of lead compound, LUT014, a topically applied, novel B-Raf inhibitor, for the treatment of radiation-induced dermatitis (RD) in patients with breast cancer....Part 1 results showed that, of the eight patients who developed grade 2 RD at baseline, 75% (7/8) had complete resolution, improving to grade 0 dermatitis, and 100% of patients had RD of 1 or 0 as assessed by the Common Terminology Criteria for Adverse Events (CTAE) after 28 days of daily, topically applied LUT014 gel....The primary endpoint of the open-label part 1 was the incidence of Treatment-Emergent Adverse Events as assessed by CTAE at 12 weeks and the data showed that LUT014 was generally well tolerated, no severe or serious adverse events occurred and no adverse events were associated with discontinuation of the study drug."

P1/2 data • Breast Cancer • Oncology • Solid Tumor

LUT014 for the Treatment of Radiation Induced Dermatitis in Breast Cancer Patients (clinicaltrials.gov) - P1/2 | N=28 | Completed | Sponsor: Lutris Pharma Ltd. | Active, not recruiting ➔ Completed

Trial completion • Breast Cancer • Dermatitis • Dermatology • Immunology • Oncology • Solid Tumor

Reducing skin toxicities from EGFR inhibitors with topical BRAF inhibitor therapy. (PubMed, Cancer Discov) - "Ten patients with metastatic colorectal cancer who had developed acneiform rash while being treated with cetuximab or panitumumab were enrolled in three cohorts. The acneiform rash improved in the six patients who started with grade 2 rash in the low and intermediate cohorts. We conclude that topical LUT014 is safe and efficacious in improving rash from EGFR inhibitors, consistent with the mechanism of action inducting paradoxical MAPK activation."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A Study of LUT014 in Patients With Metastatic Colorectal Cancer With EGFR Inhibitor Induced Acneiform Lesions (clinicaltrials.gov) - P1 | N=10 | Completed | Sponsor: Lutris Pharma Ltd. | Active, not recruiting ➔ Completed

Trial completion • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • EGFR

LUT014 for the Reduction of Dose-Limiting Acneiform Lesions Associated With EGFRI Treatment of mCRC (clinicaltrials.gov) - P2 | N=117 | Recruiting | Sponsor: Lutris Pharma Ltd. | Trial completion date: Mar 2023 ➔ Jun 2023 | Trial primary completion date: Dec 2022 ➔ Mar 2023

Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Lutris Pharma Completes Enrollment of Part Two of its Phase 1/2 Trial of LUT014 To Treat Radiation Dermatitis in Patients with Breast Cancer (PRNewswire) - "Lutris Pharma...announced that it has completed enrollment of part two of its phase 1/2 clinical trial of lead compound, LUT014, a topically applied, novel B-Raf inhibitor, for the treatment of radiation-induced dermatitis (RD) in patients with breast cancer. Top-line data is expected in the third quarter of 2022. The randomized, double-blind, placebo-controlled part two of the phase 1/2 study has enrolled a total of 20 patients and is designed to evaluate the efficacy of topically administered LUT014 in breast cancer patients with RD."

Enrollment closed • P1/2 data • Breast Cancer • Dermatitis • Oncology

LUT014 for the Treatment of Radiation Induced Dermatitis in Breast Cancer Patients (clinicaltrials.gov) - P1/2 | N=28 | Active, not recruiting | Sponsor: Lutris Pharma Ltd. | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2021 ➔ Aug 2022 | Trial primary completion date: Oct 2021 ➔ Jun 2022

Enrollment closed • Trial completion date • Trial primary completion date • Breast Cancer • Dermatitis • Dermatology • Immunology • Oncology • Solid Tumor

Lutris Pharma Expands Intellectual Property Portfolio Surrounding its Novel B-Raf inhibitors Including Lead Asset LUT014 (PRNewswire) - "Lutris Pharma...announced that it has expanded the intellectual property (IP) surrounding its novel B-Raf inhibitors, including lead compound LUT014, a topically applied, novel B-Raf inhibitor for the treatment of cutaneous reactions caused by treatment with epidermal growth factor receptor (EGFR) inhibitors and/or PI3K inhibitors and treatment of radiation dermatitis (RD) caused by radiation therapy, in both the U.S. and internationally....The company noted that a patent has been filed in the U.S., Australia, Brazil, Canada, China, EP (regional), Israel, India, Japan, Mexico, Russian Federation, South Korea and South Africa for the treatment of radiation dermatitis (RD) with B-Raf inhibitors."

Patent • Oncology

LUT014 for the Reduction of Dose-Limiting Acneiform Lesions Associated With EGFRI Treatment of mCRC (clinicaltrials.gov) - P2; N=117; Recruiting; Sponsor: Lutris Pharma Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Lutris Pharma Initiates Part Two of its Phase 1/2 Trial of LUT014 To Treat Radiation Dermatitis in Breast Cancer Patients (PRNewswire) - "Lutris Pharma...announced that, based on the compelling results observed in part one, it has initiated part two of its phase 1/2 trial of lead compound, LUT014, a topically applied, novel B-Raf inhibitor, for the treatment of radiation-induced dermatitis (RD) in breast cancer patients. Part two of the phase 1/2 study is expected to enroll a total of 20 patients (10 per part) and is designed to evaluate the efficacy of topically administered LUT014 in breast cancer patients with RD."

Trial status • Breast Cancer • Oncology

LUT014 for the Treatment of Radiation Induced Dermatitis in Breast Cancer Patients (clinicaltrials.gov) - P1/2; N=28; Recruiting; Sponsor: Lutris Pharma Ltd.; N=15 ➔ 28

Clinical • Enrollment change • Breast Cancer • Dermatitis • Dermatology • Immunology • Oncology • Solid Tumor

Lutris Pharma Doses First U.S. Patients in Phase 2 Trial of LUT014 -- a Topical Gel for the Reduction of Dose-Limiting Acneiform Lesions -- in Metastatic Colorectal Cancer Patients Treated with EGFR Inhibitor Therapy (PRNewswire) - “Lutris Pharma…announced that the first U.S. patients have been dosed as part of the Company's phase 2 trial of lead compound, LUT014, a topically applied, novel B-Raf inhibitor, for metastatic colorectal cancer patients (mCRC) being treated with epidermal growth factor receptor (EGFR) inhibitor therapy who have developed dose-limiting acneiform lesions. Recruitment and treatment of patients in Israel continues to progress…The phase 2, randomized, double-blind, placebo-controlled trial is expected to enroll a total of 117 subjects at 20 sites, consisting of 15 in the U.S. (including Memorial Sloan Kettering Cancer Center in New York) and five in Israel…‘we look forward to participating in the phase 2 trial and to the interim results later this year’."

P2 data • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Oncology

Side effect of cancer treatment can be safely reduced with topical cream - ".A majority of patients with advanced colorectal cancer are treated with these types of drugs at some point in their treatment,” said study co-author Dr. Zev Wainberg.....Dr. Antoni Ribas...developed a topical BRAF inhibitor that can be applied directly on the skin, called LUT014. They found in laboratory models that the therapy induces paradoxical MAPK activation of skin cells and offsets the negative effects of EGFR inhibitors. The cancer is being inhibited by the EGFR inhibitor, but the cream is letting the skin go back to normal by activating this pathway, said Ribas. "

Media quote

Lutris Pharma Phase 1 Results of LUT014 for Skin Toxicities Associated with Treatment of Colorectal Cancer Patients with EGFR Inhibitors Published in Cancer Discovery (PRNewswire) - P1, N=10; NCT03876106; Sponsor: Lutris Pharma; “Lutris Pharma…announced today that results of a Phase1 study for its lead product, LUT014, assessing the safety, tolerability, and efficacy of topically administered LUT014 for the treatment of epidermal growth factor receptor (EGFR) inhibitor-induced acneiform lesions in metastatic colorectal cancer patients…In all dosage levels, LUT014 was well tolerated with no dose limiting toxicities. The acneiform rash improved in all the patients who started with grade 2 rash in the low and intermediate dose cohorts (6 patients), and the improvement was maintained a month after treatment cessation…The primary outcome is the proportion of subjects in each treatment group who reached treatment success, defined as an improvement (decrease) of at least one grade in the severity of the acneiform lesions from baseline to day 28. Interim results are expected by the end of 2021.”

P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology

LUT014 for the Reduction of Dose-Limiting Acneiform Lesions Associated With EGFRI Treatment of mCRC (clinicaltrials.gov) - P2; N=117; Not yet recruiting; Sponsor: Lutris Pharma Ltd.

Clinical • New P2 trial • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor