A Blood-Based Test for EGFR Mutations in NSCLC Is Being Developed

“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.”


New Drugs Aim to Defeat Tumor Resistance to EGFR Inhibitors


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…


Results of New Drug, ASP8273, Show Response in Patients with Treatment-Resistant NSCLC

The gist: People with non-small cell lung cancer (NSCLC) that has both the EGFR and T790M mutations might benefit from a new drug. The drug is called ASP8273. A clinical trial tested ASP8273 in volunteer patients in Japan. In the trial, it shrank people’s tumors. More research is needed, but it is hoped that the drug might be a good alternative for people whose tumors are resistant to drugs like erlotinib, gefitinib and afatinib.

“In a second presentation looking at new ways of treating non-small cell lung cancer (NSCLC) that has both the EGFR and T790M mutations, researchers will tell the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain, that an oral drug called ASP8273 has caused tumour shrinkage in patients in a phase I clinical trial in Japan.

“Mutations of the epidermal growth factor (EGFR) occur in about 30-35% of Asian patients with NSCLC (and in 10-15% of Caucasian patients). EGFR inhibitors called tyrosine kinase inhibitors (TKI), such as erlotinib, gefitinib and afatinib, can be used to treat EGFR-mutated NSCLC. However, these patients will eventually develop resistance to EGFR TKI therapy, rendering their disease resistant to current treatments. A further mutation called T790M accounts for 60% of this acquired resistance.

“ASP8273 is a new drug that inhibits the EGFR mutation and the T790M resistance mutation. Earlier research in mice had shown that it caused NSCLC to disappear completely, and so a I clinical trial was started in January 2014 to assess the drug’s safety and efficacy in humans.

“Twenty-four Japanese patients have enrolled so far to receive one of six levels of doses (25, 50, 100, 200, 400 and 600mg) once a day. A further seven patients have been enrolled into a second group to evaluate doses of 100mg, 200mg and 400mg a day (a dose escalation study), and the researchers are planning to enrol a total of 124 patients. Cancer had progressed in all the patients after prior treatment with EGFR TKI therapy, and most of them had the T790M mutation.”


Clovis Oncology Enters Into Oncology Clinical Trial Collaboration With GlaxoSmithKline

The gist: Scientists hope that a promising drug called rociletinib could be combined with a drug called trametinib to treat people with non-small cell lung cancer (NSCLC) whose tumors have mutations in the EGFR gene. Both drugs are targeted therapy drugs. The combination might help treat people whose tumors are resistant to other targeted treatments, due to EGFR T790M mutations. The combination will be tested soon in a clinical trial with volunteer patients. Later, other clinical trials might try combining rociletinib with other drugs.

“ ‘We have seen significant activity in EGFR mutant NSCLC patients treated with rociletinib monotherapy, and so an important next step in our research is to examine rociletinib in combination with other targeted therapies that may also impact acquired resistance to EGFR inhibitors,’ said Lecia V. Sequist, MD, MPH, Massachusetts General Hospital Cancer Center and Associate Professor of Medicine at Harvard Medical School and the lead investigator for this combination study.

“ ‘As we continue to see compelling activity for rociletinib single-agent therapy at our selected dose, we look forward to exploring combination trials in both T790M-positive and T790M-negative patients,’ said Patrick J. Mahaffy, President and CEO of Clovis Oncology. ‘We believe that given the tolerability profile of rociletinib, particularly its lack of cutaneous toxicity, it may be a good candidate for combination therapy with trametinib, and other relevant targeted therapies. We intend to announce additional combination studies over the next few months.’ “


Clovis Oncology (CLVS) Says First Patient Enrolled in Phase 2 TIGER-1 Study

The gist: In a clinical trial, the first patient has been given a new drug called rociletinib to treat their non-small cell lung cancer (NSCLC). All volunteer patients in the trial have tumors with mutations in the EGFR gene, including a mutation called T790M that makes them resistant to treatment with other EGFR-targeted drugs. It is hoped that rociletinib will prove to be a good option, in terms of survival and side effects, for these patients.

“Clovis Oncology (NASDAQ: CLVS) announced today that the Phase 2 portion of the seamless Phase 2/3 TIGER-1 (Third-Generation Inhibitor of Mutant EGFR in Lung Cancer) study has commenced with the dosing of the first patient at a U.S. study site. Rociletinib is 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 primary resistance mutation T790M.

“ ‘I am pleased to lead the US trial of first-line rociletinib in patients with EGFR-mutant NSCLC,’ said Ross Camidge, MD, PhD, Associate Professor, Division of Medical Oncology, University of Colorado School of Medicine and the lead investigator for the TIGER-1 study in the United States. ‘The rociletinib clinical data observed to date in the second-line EGFR-mutant population after failure of drugs like erlotinib have been highly encouraging and consistent, really making the case to try this drug in these patients from the outset. The absence of side effects associated with wild-type EGFR inhibition from this drug is also likely to be welcomed by patients.’ “


Clovis Launches TIGER2 Trial for CO-1686 in Previously Treated T790M-Positive NSCLC Patients

“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.


At ASCO, Next-Gen EGFR Inhibitors Show Early Promise in Lung Cancer Patients with T790M Mutations

“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.


ASCO 2014 Lung Cancer Roundup


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 Report Double Dose of Promising Lung Cancer Findings

“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.