“The FDA granted priority review to a new drug application for rociletinib.
“Rociletinib (Clovis Oncology) — a novel, oral, targeted covalent mutant-selective epidermal growth factor receptor inhibitor — is intended for patients with advanced EGFR-mutant, T790M-positive non–small cell lung cancer who already received EGFR-targeted therapy.
“The FDA is expected to make a decision about the agent’s status by March 30, 2016.”
“A new drug application (NDA) has been submitted for rociletinib (CO-1686) as a treatment for patients with EGFR T790M-positive metastatic non–small cell lung cancer (NSCLC) following prior administration of an EGFR TKI, according to a statement from the drug’s developer, Clovis Oncology.
“The NDA was preceded by a breakthrough therapy designation for the potent mutant-selective EGFR inhibitor in May 2014. The application was based on findings from the ongoing phase I/II TIGER-X trial, which were published in The New England Journal of Medicine and updated at the 2015 ASCO Annual Meeting. In patients with T790M-mutant NSCLC by tissue testing (n = 243), the objective response rate (ORR) across all dose levels was 53% and the disease control rate (DCR) was 85%.
“An application for premarket approval (PMA) is anticipated for Qiagen’s therascreen EGFR RGQ PCR Kit as a companion diagnostic (CDx) for rociletinib, according to the statement. The therascreen EGFR test was initially approved in 2013 as a CDx for afatinib (Gilotrif) and recently received a new indication as a CDx for gefitinib (Iressa).”
“Clovis Oncology (NASDAQ:CLVS) announced today updated findings from its Phase 2 clinical study of rociletinib (CO-1686), the Company’s novel, oral, targeted covalent (irreversible) mutant-selective inhibitor of the epidermal growth factor receptor (EGFR) for the treatment of non-small cell lung cancer (NSCLC) in patients with initial activating EGFR mutations, as well as the dominant resistance mutation T790M. These data from the TIGER-X trial are being presented today in an oral presentation (Abstract #8001) at the 2015 American Society of Clinical Oncology (ASCO) annual meeting in Chicago.
“ ‘The maturing data for rociletinib confirm in a large patient population what we have seen in our early clinical experience,’ said Jonathan Goldman, MD, TIGER-X investigator and Assistant Professor, UCLA Hematology & Oncology, Associate Director of Drug Development and Director of Clinical Trials in Thoracic Oncology. ‘Rociletinib has shown very encouraging and durable activity in the most advanced mutant EGFR lung cancer patients, including in a large population of patients with CNS metastases. Importantly, the data continue to show activity in both T790M-positive and T790M-negative patients, which gives us a potential treatment option for all patients who have progressed on their initial EGFR targeted therapy.’ “
“Clovis Oncology is evaluating a blood-based assay to detect EGFR mutations in circulating tumor DNA in non-small cell lung cancer patients as a way to better identify candidates for treatment with rociletinib (CO-1686), its investigational EGFR inhibitor, a Clovis scientist said this week.
“During a talk at the Cambridge Healthtech Institute Molecular Medicine Tri-Conference held here, Chris Karlovich, principal scientist for molecular diagnostics at Clovis, said that his company is comparing the performance of Sysmex Inostics’ BEAMing assay service to that of Qiagen’s TheraScreen EGFR PCR test in a subset of patients from the company’s “third-generation inhibitor of mutant EGFR lung cancer” (TIGER) clinical trial for rociletinib.
“The goal, Karlovich said, is to overcome some of the limitations of tissue-based PCR testing in identifying EGFR mutations, particularly the T790M resistance mutation, which can be used to identify patients who have become resistant to EGFR-directed therapy and thus are candidates for second- or later-line treatment with rociletinib. In addition, Karlovich said, blood-based assays like BEAMing could potentially be used to more easily monitor response to the drug.
“Rociletinib was designed to selectively target initial activating EGFR mutations and the T790M resistance mutation, while sparing wild-type EGFR at anticipated therapeutic doses, with an improved toxicity profile, according to Clovis’ website.”
In recent years, many people with non-small cell lung cancer (NSCLC) have been successfully treated with drugs called EGFR inhibitors. But over time, most patients develop resistance, and the drugs stop working. Researchers are hard at work developing new drugs to help patients who can no longer be treated with EGFR inhibitors.
EGFR inhibitors get their name from a gene called EGFR. Many lung cancer tumors have mutations in this gene. These mutations convert EGFR from a normal gene into a cancer gene that initiates and promotes cancer growth. Approximately 10% to 15% of white and 30% to 35% of Asian patients with NSCLC have EGFR mutations. Continue reading…
“Clovis Oncology has launched the TIGER2 study for its non-small cell lung cancer drug CO-1686, an agent the company is studying as a treatment for advanced patients with tumors characterized by EGFR mutations and the T790M resistance mutation.
“CO-1686 is an irreversible EGFR inhibitor. Clovis this week said it has dosed the first patient in the TIGER2 Phase I/II trial, which is focused on gauging the efficacy of CO-1686 in NSCLC patients who have progressed on their first and only anti-EGFR treatment.”
Editor’s note: Some people with advanced non-small cell lung cancer (NSCLC) have tumor cells with mutations in the EGFR gene (oncologists often use a tumor biopsy to check for this mutation in a patient). These patients can be treated with targeted drugs known as EGFR inhibitors. EGFR inhibitors can shrink tumors at first, but over time, tumors may become resistant to the drugs and start growing again. Often, this is because of a new, additional mutation that occurs in the EGFR gene called T790M. A new clinical trial is enrolling volunteer patients with the T790M mutation to test a new drug meant to overcome EGFR inhibitor resistance. The drug is called CO1-686.
“Next-generation EGFR inhibitors for treating metastatic non-small cell lung cancer patients who have acquired resistance to first-generation drugs in this class accurately hit mutant EGFR tumor cells and caused fewer serious side effects, early data presented at a major cancer conference showed.
“Researchers at the American Society of Clinical Oncology’s annual meeting here this week, presented preliminary data from human studies on three next-generation EGFR inhibitors: AstraZeneca’s AZD9291, Clovis Oncology’s CO-1686, and Hanmi Pharmaceutical’s HM61713. All three agents showed promising activity against patients who had EGFR mutations, had received prior treatment with a first-generation tyrosine kinase inhibitor – such as Roche’s Tarceva (erlotinib) and AstraZeneca’s Iressa (gefinitib) – and had T790M mutations.”
Editor’s note: For a more reader-friendly explanation of these new drugs, check out the “Drug resistance” section of our Chief Scientist’s latest blog post.
Every year, thousands of people gather in Chicago, Illinois, for the American Society of Clinical Oncology (ASCO) Annual Meeting. The largest meeting of its kind, ASCO brings together doctors, researchers, nurses, patient advocates, pharmaceutical company representatives, and more to discuss the latest in cancer research. Here are some of the most exciting new developments in lung cancer research presented last week at ASCO 2014: Continue reading…
“Researchers with UCLA’s Jonsson Comprehensive Cancer Centerreport that two new experimental drugs have shown great promise in the treatment of patients with non–small-cell lung cancer, which accounts for about 85 percent of all lung cancers. Lung cancer is the leading cause of cancer death in the United States.
“The drugs—ramucirumab and CO-1868—were shown in separate clinical trials to increase survival times with fewer toxic side effects than standard treatments. The findings were presented this week at the American Society of Clinical Oncology annual meeting in Chicago.”
Editor’s note: For more on the ramucirumab findings, see our previous news post. To learn more about targeted therapies like CO-1686 and ramucirumab, visit our lung cancer Basics.