RET-driven cancer new treatment! Lilly Retevinib ™ has been approved by the U.S. FDA, becoming the first treatment for patients with advanced lung cancer and thyroid cancer with reT-driven genes

May 9, 2020, Lilly Pharmaceuticals (NYSE: LLY) announced that the U.S Food and Drug Administration (FDA) approved the Retevmo ™ (elpercatinib 40 mg, 80 mg capsule), the first approved specifically for the treatment of transfection recital gene (RET) fusion-positive non-transferable Adult patients with small cell lung cancer (NSCLC), and patients with advanced or metastatic thyroid myelin cancer with RET mutations and children 12 years of age and older who require systematic treatment and radioactive iodine treatment (if applicable) are difficult to treat in adults with advanced or metastatic thyroid cancer and children 12 years of age Benefiting from the FDA's accelerated review channel, Retevmo ™'s approval is based on the objective mitigation rate (ORR) and mitigation duration (DoR) of the LIBRETTO-001 I/II clinical trials Follow-up full approval of these indications depends on the confirmation of their clinical effectiveness in validated trials Retevmo is an oral selective RET kinase inhibitor Retevmo acts on both tumor cells and normal cells, which can lead to drug side effects "In clinical trials, we observed that most patients with metastatic lung cancer, including those with refractory brain metastasis, experienced clinically significant remission when treating elpercatinib," said Dr Alexander Drilon, lead researcher on early drug development at memorial Sloan Kettering Cancer Center in the United States .
The approval of Selpercatinib is an important milestone in NSCLC treatment, which allows cancerd with RET gene variants to be targeted in whole-stage treatments like cancers with activated EGFR and ALK changes I am pleased that these RET-driven cancer treatments have a new option Retevmo was evaluated in the single-arm multicenter I/II LIBRETTO-001 trial, the largest clinical trial in ret-driven cancer patients." The clinical trial included both primary treatment patients and treated patients with a variety of advanced solid tumors, including RET fusion-positive NSCLC, RET-mutated MTC, RET fusion-positive thyroid cancer, and other RET-altered solid tumors The main outcomes are ORR and DoR, which are evaluated by an independent evaluation committee Preset secondary research endpoints include central nervous system (CNS) ORR and CNS DoR NR-
thyroid cancer includes: papilloma, Hurthle cells, undifferentiated, low-differentiated brain metastasis in non-small cell lung cancer patients with up to 50% RET fusion-positive In treated NSCLC patients with detectable brain metastasis, 10 out of 11 patients observed intracranial lesions (CNS ORR), and CNS DoR in all 10 patients was 6 months Warnings and precautions in Retevmo's notes include: hepatotoxicity (evidence of abnormal liver function), hypertension, prolonged QT intervals, bleeding events, allergic reactions, risk of poor wound healing, and fetal toxicity of embryos in the LIBRETTO-001 trial, the discontinuation rate due to adverse reactions (AR) was 5% The most common adverse reactions ( In addition, the most common severe adverse reactions (-2%) were elevated ALT, AST and pneumonia No other serious adverse reactions were reported in more than 2% of patients " most patients with thyroid myelin-like cancer and a significant proportion of other thyroid cancers have RET changes For these cancer patients, the approval of elpercatinib means that they now have a treatment that selectively and effectively inhibits RET," said Dr Lori J Wirth, medical director of head and neck cancer at Massachusetts General Hospital Cancer Center Anne White, President of Lilly Oncology, , said, "We are pleased that the combined team of Loxo Oncology and Lilly Oncology has brought Retevmo to patients so quickly, further demonstrating our commitment to providing life-changing drugs to cancer patients Retevmo entered clinical trials in May 2017 and is now approved in less than three years, the fastest time in the industry to develop a number of anindication-disease tumor drugs Retevmo's approval is particularly important for patients with advanced or metastatic RET-driven lung and thyroid cancer, and we would like to thank the FDA for its guidance and assistance! "
Retevmo is only available in patients with advanced or metastatic NSCLC or thyroid cancer with RET fusion, or in patients with advanced or metastatic thyroid myeloid cancer with RET mutation This needs to be determined by biomarker detection Next-generation sequencing (NGS) through tumor tissue biopsies or liquid biopsies can be used as appropriate biomarker senotosis to identify genetic changes, including RETs If detection through NGS is not possible, RET can be detected using other biomarker detection methods There is currently no FDA-approved test method for detecting RET fusion and RET mutations In LIBRETTO-001, local laboratories used NGS, PCR, or FISH to pre-determine RET gene changes in plasma or tumor tissue Immunohistochemistry is not used in these clinical trials Andrea Ferri, President and CEO of LUNGevity, said: "Through the use of comprehensive biomarker testing, metastatic cancer patients are increasingly gaining access to treatments tailored to the specific genetic properties of their tumors As the first approved treatment specifically for RET-driven tumor patients, Retevmo represents an important new development in this developing area Patients are encouraged to ask a doctor about a wide range of biomarker tests, including RET changes "
Retevmo is qualified by the FDA as an orphan drug for the treatment of RET fusion-positive NSCLC and the treatment of RET fusion-positive and RET mutations in thyroid cancer, including low-differentiated thyroid cancer, undifferentiated or interstitated thyroid cancer, thyroid myelin cancer and localized advanced or metastatic or papyl thyroid cancer Two confirmed Phase III trials (LIBRETTO-431 and LIBRETTO-531) are currently recruiting patients Retevmo ™ (elpercatinib) Retevmo (elpercatinib, formerly known as LOXO-292) is an oral, highly selective, powerful RET kinase inhibitor Retevmo acts on both tumor and healthy cells, which can cause side effects of the reT-driven cancer RET kinase genome changes include fusion and activation point mutations that lead to reT signal inactivity and uncontrolled cell growth RET fusion was found in approximately 2% of NSCLCs, as well as 10-20% of nipple-like, Hurthle cells, undifferentiated and low-differentiated thyroid cancers Activated RET point mutations accounted for about 60% periage mTC and 90% family MTC The proliferation and survival of RET fusion-positive cancers and RET mutant MTC depend solely on this single activated kinase This dependence, often referred to as "cancer gene addiction," is highly affected by targeted RET small molecule inhibitors RET-driven changes are largely mutually exclusive with other cancer drivers the largest clinical trial of RET inhibitors to treat RET-driven cancer patients in liBRETTO-001
LIBRETTO-001 I/II clinical trials The test includes the dose increment phase (phase I) and the dose expansion phase (phase II) Phase II trials cover the main therapeutic outcomes ORR and DoR, as well as the pre-set secondary study endpoints being CNS ORR and CNS DoR, which are determined by the Independent Review Committee in accordance with the Physical Tumor Response Assessment Standard (RECIST v1.1) The NSCLC population study was presented at the 2019 IASLC World Lung Cancer Congress (WCLC), while the thyroid population study was presented at the 2019 European Society of Medical Oncology (ESMO) Congress Source: , Drilon A, Lin JJ, Filleron T, et al Frequency y of brain metatae and multikinae outcome pondel in patient ret rearranged lung cancer J Thorac Oncol 2018;13(10):1595-1601