Trial of LUT014 for Radiation-Induced Dermatitis Completes Enrollment

Enrollment has been completed for part 2 of a phase 1/2 trial (NCT04261387) of LUT014, a treatment for radiation-induced dermatitis (RD) in patients with breast cancer, according to a press release from Lutris Pharma.¹

LUT014, a topically applied novel BRAF inhibitor, demonstrated positive results in reducing severity of RD in the first part of the trial. This led to the early initiation of the phase 2 part of the trial, which randomized patients to receive LUT014 or placebo.

"The strong results observed from the 8 patients in part 1 of the trial of LUT014 to treat RD gave us additional confidence in the potential of this therapy and spurred us to begin part 2 earlier than anticipated," Benjamin W. Corn, MD, chief medical officer of Lutris Pharma, said in a statement. "There remains a significant unmet need among patients with breast cancer who suffer from RD, for whom there are currently no approved treatment options. LUT014 has a unique mechanism of actions which aims to balance the destruction of cells in the basal layer of the skin by enhancing cell proliferation, thus potentially reversing the effects of RD."

In part 2, 20 patients who experienced grade 2 RD following completion of fractionated radiation therapy for breast cancer were randomized 1:1 to receive topically administered LUT014 gel or a placebo once daily for 28 days with a 2-month follow-up period. Part 2 is double blinded, while part 1 was open label.

The primary end point is the change in RD severity based on a self-reporting questionnaire of Dermatology Life Quality Index (QoL) at 14 days. A secondary end points is the incidence of treatment-emergent adverse events by the Common Terminology Criteria for Adverse Events (CTCAE) grading scale from baseline to 12 weeks.

There is no currently approved treatment that is indicated for RD, a condition that can reduce patients’ quality of life or limit the use of radiotherapy. Lutris Pharma plans to present topline data from the study in the third quarter of 2022.

LUT014 is also being investigated as treatment for EGFR inhibitor-related skin toxicities in patients with metastatic colorectal cancer. Phase 1 trial (NCT03876106) results reported in Cancer Discovery showed that low and intermediate doses of LUT014 were able to reduce dose-limiting acneiform lesions in 6 patients with grade 2 rash with effects lasting at least a month after the end of treatment with LUT014.² A randomized phase 2 trial (NCT04759664) of 117 patients began dosing in August 2021 to validate these results versus a placebo.³ 

"Enrollment of the last patient in the blinded part 2 portion of our phase 1/2 study brings us one step further in the clinical development of LUT014 as a treatment for RD," Noa Shelach, PhD, chief executive officer of Lutris Pharma, said in a press release.¹ "It is estimated that approximately half of [patients with] cancer are treated with radiation therapy, annually, and the majority of [patients with] breast cancer, in particular, experience some form of RD. Based on the mechanism of action of LUT014, we believe that LUT104 may have a significant impact on this patient population. We look forward to reporting robust data from this trial in the third quarter of this year."

_References:

_{1. Lutris Pharma completes enrollment of part two of its phase 1/2 trial of LUT014 to treat radiation dermatitis in patients with breast cancer. PR Newswire. Published April 6, 2022. Accessed April 7, 0222. https://prn.to/3DSJ6f7}

_{2. Lacouture ME, Wainberg ZA, Patel AB, et al; Reducing skin toxicities from EGFR inhibitors with topical BRAF inhibitor therapy. Cancer Discov. 2021;11(9)2158–2167. doi:10.1158/2159-8290.CD-20-1847}

_{3. 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. PR Newswire. Published August 3, 2021. Accessed April 7, 2022. https://prn.to/3r9l9uY}