Panitumumab

LUT014 Gel Provides a Statistically Significant Benefit Over Placebo for the Treatment of Acneiform Rash Associated With Cetuximab or Panitumumab Therapy For Patients With Advanced Colorectal Cancer TEL AVIV, Israel, July 7, 2025 /PRNewswire/ -- Lutris Pharma, a clinical stage biopharmaceutical company focused on improving anti-cancer therapies by reducing cutaneous dose limiting toxicities, today announced the presentation of results from its double-blind, placebo-controlled phase 2 randomized clinical trial of lead compound, LUT014 gel. 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) Gastrointestinal Cancers Congress 2025. "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 Annual Meeting, the selection of our LUT014 data for oral presentation at the ESMO 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. 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. About Lutris Pharma Lutris Pharma is a clinical stage biopharmaceutical company focused on improving anti-cancer therapy effectiveness and quality of life for patients who are being treated with EGFR (Epidermal Growth Factor Receptor) inhibitors or with radiation, where dermal toxicity often leads to a reduction of anti-cancer therapy compliance. The company aims to provide novel topical therapies in order to mitigate these side effects. Lutris Pharma's lead asset, LUT014, a topical B-Raf Inhibitor, is a proprietary, first-in-class, small molecule, which has completed enrollment in a phase 2 clinical trial in metastatic colorectal cancer patients with EGFR inhibitor induced acneiform lesions and has successfully completed a phase 1/2 study for the treatment of radiation-induced dermatitis in breast cancer patients. For more information, please visit . Contacts: Lutris Pharma Sumant Ramchandra, M.D., Ph.D. Chief Executive Officer [email protected] Noa Shelach, Ph.D. Chief Operating Officer [email protected] Rx Communications Group Michael Miller +1-917-633-6086 [email protected] SOURCE Lutris Pharma WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

ESMO GI 2025微专辑扫描二维码可查看更多内容编者按在2025年欧洲肿瘤内科学会（ESMO）胃肠癌大会（7月2~5日，巴塞罗那）上展示的PARERE和OrigAMI-1试验数据表明，通过不同抑制方法进行的ctDNA指导的抗EGFR再挑战策略，在RAS/BRAF野生型转移性结直肠癌（mCRC）中是一种有效的策略。在Ⅱ期PARERE试验中，对213例难治性肿瘤患者（这些患者对一线抗EGFR治疗有反应）而言，使用帕尼单抗进行抗EGFR治疗后在疾病进展时改用瑞戈非尼的治疗方案，比相反的治疗顺序效果更好（摘要4O）。与瑞戈非尼相比，帕尼单抗的客观缓解率（ORR）更高（16% vs. 2%；P<0.001），疾病控制率（DCR）也更高（59% vs. 32%；P<0.001）。帕尼单抗的无进展生存期1（PFS1）为4.1个月，而瑞戈非尼为2.4个月（P=0.116）。在精选的ctDNA RAS/BRAF野生型患者中，帕尼单抗的无进展生存期优势更为明显；在19例至少有1种抗EGFR耐药突变的患者中，帕尼单抗和瑞戈非尼之间没有差异。图1. 在PARERE试验中，难治性ctDNA RAS/BRAF野生型mCRC患者疾病进展时使用帕尼单抗后改用瑞戈非尼与相反治疗顺序的疗效对比来自Ib/II期OrigAMI-1试验的更新结果显示，在54例左侧ctDNA RAS/BRAF野生型mCRC患者中（摘要6MO），在更长的时间间隔（>8.8个月vs.≤8.8个月）后再次使用EGFR-MET双特异性抗体amivantamab单抗进行再挑战，可使客观缓解率（32% vs. 7%）和中位无进展生存期（7.0个月vs. 2.8个月；P=0.0081）得到改善，并且总体生存期（OS）有延长的趋势（16.1个月vs.10.4个月；P=0.088），基线ctDNA突变分析不能预测治疗反应。英国利兹大学的珍妮·塞利格曼教授说：“这两项试验中取得的缓解率在经过多线预处理的情况下是有意义的，PARERE试验中的疾病控制率非常令人鼓舞。这些结果在更大型、随机的试验环境中证实了之前报道的小型单臂CHRONOS研究的结果。”在大会上还展示了一项来自西班牙的回顾性研究，研究对象为134例RAS/BRAF野生型mCRC患者，结果表明，较长的既往抗EGFR无进展生存期（>20个月）和抗EGFR治疗间歇期（>10.4个月）分别与更好的疾病控制率（P=0.04和P<0.01）、无进展生存期（P=0.01和P<0.01）相关。EGFR治疗间歇期还与总生存期相关（P<0.01），相比之下，较短的间隔则没有这些效果（摘要42P）。塞利格曼认为，研究治疗之间的理想间隔很重要，令她感到欣慰的是，再挑战的效果延伸到了临床治疗的患者身上，尽管该队列是在高度专业化的专家中心接受治疗的。目前这是一个非常活跃的研究领域，新的数据“推动抗EGFR再挑战方法向标准治疗迈进”。不过，她强调还需要更多的研究和考虑：“未来的挑战包括正式确定抗EGFR再挑战在治疗路径中的时间安排，以及ctDNA指导再挑战的时间安排。此外，尽管这些数据令人兴奋，但我们应该记住，液体活检指导的治疗对患者的可及性可能比较有限，因为许多中心无法获得必要的ctDNA技术。”参考来源Ciracì P, et al. Liquid biopsy-guided selection for anti-EGFR re-treatment in RAS/BRAF wild-type (wt) chemorefractory metastatic colorectal cancer patients (mCRC pts): Results from the phase II randomized PARERE trial. ESMO Gastrointestinal Cancers Congress 2025, Abstract 4OProffered Paper Session 2, 04.07.2025, h. 16:30 – 18:00, Room MadridArnold D, et al. Rechallenge with amivantamab, an EGFR-MET bispecific antibody, after disease progression on prior EGFR inhibitor in left-sided RAS/BRAF wild-type metastatic colorectal cancer: Updated results from OrigAMI-1. ESMO Gastrointestinal Cancers Congress 2025, Abstract 6MOMini Oral Session – Innovation in Gl Cancers, 02.07.2025, h. 16:15 – 17:35, Room BarcelonaMascaró Baselga P, et al. Real-world outcomes of anti-EGFR rechallenge in RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC). ESMO Gastrointestinal Cancers Congress 2025, Abstract 42PPoster Display Session 2, 04.07.2025, h. 15:30 – 16:30, Foyer（来源：肿瘤瞭望消化时讯）声 明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。