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

Clovis Launches TIGER2 Trial for CO-1686 in Previously Treated T790M-Positive NSCLC Patients | Lung Cancer Dispatch | Scoop.it

"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.
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Pharmacogenomics Reporter  |  Jun 25, 2014

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Resistance to Lung Cancer Targeted Therapy Can be Reversed, Study Suggests

Resistance to Lung Cancer Targeted Therapy Can be Reversed, Study Suggests | Lung Cancer Dispatch | Scoop.it

"Up to 40 percent of lung cancer patients do not respond to a targeted therapy designed to block tumor growth—a puzzling clinical setback that researchers have long tried to solve. Now, scientists at Georgetown Lombardi Comprehensive Cancer Center and the National Cancer Institute have discovered why that intrinsic resistance occurs—and they pinpoint a drug they say could potentially reverse it."


"Their findings, published in the Journal of Clinical Investigation, found that over-expression of the growth protein Cripto-1 makes lung cancer cells resistant to the drug erlotinib (Tarceva®). Experiments in cell lines and in animals demonstrated that blocking Cripto-1 signaling transduction restored sensitivity to the drug, one of a number of EGFR inhibitors used in non-small cell lung carcinoma and other cancers."


Editor's note: Lung cancer patients who try the targeted therapy drug erlotinib (brand name Tarceva) may be intrinsically resistant to it; it has no effect on their tumor growth. Researchers have now found that abnormalities involving a gene called Cripto-1 can make a tumor resistant to Tarceva, and that drugs that block Cripto-1's role in tumor cells can restore sensitivity to Tarceva. These studies were done on human cancer cells in the lab and in animals, but a new clinical trial with volunteer patients will test whether a drug called AZD0424 might undo Tarceva resistance in patients with non-small cell lung cancer (NSCLC), allowing them to benefit from Tarceva treatment.

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Medical Xpress  |  Jun 9, 2014

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'Liquid Biopsy' Offers New Way to Track Lung Cancer

'Liquid Biopsy' Offers New Way to Track Lung Cancer | Lung Cancer Dispatch | Scoop.it

"Scientists have shown how a lung cancer patient's blood sample could be used to monitor and predict their response to treatment – paving the way for personalised medicine for the disease.


"The recent study, published in the journalNature Medicine, also offers a method to test new therapies in the lab and to better understand how tumours become resistant to drugs.


"Small cell lung cancer (SCLC) is an aggressive disease with poor survival and new treatments are desperately needed. In many cases the tumour is inoperable and biopsies are difficult to obtain, giving scientists few samples with which to study the disease."

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Medical Xpress  |  Jun 3, 2014

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ARIAD Presents Updated Phase 1/2 Data on AP26113 in Patients with ALK+ Non-Small Cell Lung Cancer

ARIAD Presents Updated Phase 1/2 Data on AP26113 in Patients with ALK+ Non-Small Cell Lung Cancer | Lung Cancer Dispatch | Scoop.it

"ARIAD Pharmaceuticals, Inc. today announced updated clinical results on its investigational tyrosine kinase inhibitor (TKI), AP26113, in patients with advanced non-small cell lung cancer (NSCLC) from an ongoing Phase 1/2 trial. These study results show anti-tumor activity of AP26113 in patients with crizotinib-resistant anaplastic lymphoma kinase (ALK) positive NSCLC, including patients with brain metastases. Crizotinib is approved for ALK-positive NSCLC patients."


Editor's note: This story is about a targeted drug called AP26113, which may benefit some patients with advanced non-small cell lung cancer (NSCLC). Specifically, it has shown promise for those patients whose tumors have mutations in the ALK gene, as detected by molecular testing, and who have already been treated with the drug crizotinib (Xalkori) but have grown resistant to it.

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MarketWatch  |  May 31, 2014

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Clovis Oncology Receives Breakthrough Therapy Designation for CO-1686
for the Treatment of Second-line EGFR Mutant Non-small Cell Lung Cancer
(NSCLC) in Patients with the T790M Mutation

Clovis Oncology Receives Breakthrough Therapy Designation for CO-1686 <br/>      for the Treatment of Second-line EGFR Mutant Non-small Cell Lung Cancer <br/>      (NSCLC) in Patients with the T790M Mutation | Lung Cancer Dispatch | Scoop.it

"Clovis Oncology, Inc. announced today that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for the Company’s investigational agent CO-1686 as monotherapy for the treatment of second-line EGFR mutant NSCLC in patients with the T790M mutation. The Breakthrough Therapy designation was granted based on interim efficacy and safety results from an ongoing Phase 1/2 study of CO-1686. CO-1686 is the Company’s novel, oral, targeted covalent (irreversible) inhibitor of mutant forms of the epidermal growth factor receptor (EGFR) for the treatment of non-small cell lung cancer in patients with initial activating EGFR mutations as well as the dominant resistance mutation T790M."


Editor's note: CO-1686 is a targeted therapy drug that is meant to treat patients whose tumors have mutations in the EGFR gene, as detected by molecular testing. Some tumors with EGFR mutations become resistant to first-line treatment and develop a new mutation called T790M. Evidence shows that non-small cell lung cancer (NSCLC) patients with T790M may benefit from second-line treatment with CO-1686.The drug has received a Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA). This means that the FDA finds CO-1686 to be very promising compared to currently available treatments for T790M-mutated NSCLC, and will accelerate the approval process that would ultimately permit oncologists to prescribe the drug outside of a clinical trial.

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MarketWatch  |  May 19, 2014

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DNA Shed by Tumors Shows Promise for Non-Invasive Screening and Prognosis

DNA Shed by Tumors Shows Promise for Non-Invasive Screening and Prognosis | Lung Cancer Dispatch | Scoop.it

"Certain fragments of DNA shed by tumors into the bloodstream can potentially be used to non-invasively screen for early-stage cancers, monitor responses to treatment and help explain why some cancers are resistant to therapies, according to results of an international study led by Johns Hopkins Kimmel Cancer Center investigators.


"Analyzing blood samples from 640 patients with various cancers, the researchers used digital polymerase chain reaction-based technology (a sophisticated method of multiplying and measuring the number DNA molecules) to evaluate how well the DNA fragments predicted the presence of tumors in the patients."

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Medical Xpress  |  Mar 6, 2014

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Medical Xpress  |  Mar 6, 2014

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Medical Xpress  |  Mar 6, 2014

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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.

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GenomeWeb  |  Jun 4, 2014

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Researchers Report Double Dose of Promising Lung Cancer Findings

Researchers Report Double Dose of Promising Lung Cancer Findings | Lung Cancer Dispatch | Scoop.it

"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.

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Medical Xpress  |  Jun 5, 2014

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ASCO: Zykadia Works Before or After Targeted Lung Ca Tx

ASCO: Zykadia Works Before or After Targeted Lung Ca Tx | Lung Cancer Dispatch | Scoop.it

Ceritinib (Zykadia) produced good response in non-small cell lung cancer (NSCLC) overexpressing ALK, regardless of prior treatment for that target, an early phase trial showed.


Ceritinib was associated with an overall response rate of 55% in patients previously treated with crizotinib (Xalkori) and 66% in those naive to that ALK inhibitor, Dong-Wan Kim, MD, of the Seoul National University Hospital, and colleagues found.

Editor's note: This article is about a drug called ceritinib (brand name Zykadia), which was recently approved by the U.S. Food and Dug Administration (FDA), allowing doctors in the U.S. to prescribe it to patients who 1) have advanced non-small cell lung cancer (NSCLC), 2) have tumor cells with mutations in the ALK gene, as detected by molecular testing, and 3) have tried treatment with crizotinib (Xalkori) but experienced worsening of their cancer. According to the new research described in this article, ceritinib may actually be beneficial whether or not the patient was previously treated with crizotinib.
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MedPage Today  |  Jun 3, 2014

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Drug-Target Database Lets Researchers Match Old Drugs to New Uses

"There are thousands of drugs that silence many thousands of cancer-causing genetic abnormalities. Some of these drugs are in use now, but many of these drugs are sitting on shelves or could be used beyond the disease for which they were originally approved. Repurposing these drugs depends on matching drugs to targets. A study recently published describes a new database and pattern-matching algorithm that allows researchers to evaluate rational drugs and drug combinations, and also recommends a new drug combination to treat drug-resistant non-small cell lung cancer."

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Science Daily  |  May 22, 2014

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New EGFR Inhibitor AZD9291 Shows Promising Activity in Treatment-Resistant Non–Small Cell Lung Cancer

New EGFR Inhibitor AZD9291 Shows Promising Activity in Treatment-Resistant Non–Small Cell Lung Cancer | Lung Cancer Dispatch | Scoop.it

"Findings from a phase I study of a new mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, AZD9291, point to a promising new treatment option for patients with advanced, EGFR-mutant, non–small cell lung cancer (NSCLC) that is resistant to standard EGFR inhibitors. Roughly 50% of patients experienced tumor shrinkage, and the drug worked particularly well in patients with the T790M mutation (detected in 60% of patients), which causes the most common form of EGFR therapy resistance. The study was presented at a presscast in advance of the 2014 ASCO Annual Meeting (Abstract 8009^)."


Editor's note: This story is about a new targeted therapy drug called AZD9291 that is designed to attack tumors with a mutation in the EGFR gene, as detected by molecular testing. In particular, it is designed for patients who are resistant to other so-called EGFR inhibitors as a result of developing a particular EGFR mutation known as T790M. In a clinical trial to test the drug in patients, it was found to show promising results for patients with advanced non-small cell lung cancer (NSCLC) with EGFR mutations, and even better results in patients with the T790M mutation.

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The ASCO Post  |  May 14, 2014

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Enhancement of Chemotherapy by Prevention of Tumor Cell Repair

"The body naturally tries to repair lesions in the DNA of tumor cells, and thus reduces the efficacy of chemotherapy. Blocking the mechanisms for DNA repair would help to potentiate chemotherapy by reducing the resistance of cells to treatment. A team of scientists has discovered a new drug that inhibits repair: spironolactone, which seems likely to be used in the very short term as an adjuvant to chemotherapy."

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ScienceDaily  |  Feb 20, 2014

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ScienceDaily  |  Feb 20, 2014

Cancer Commons's curator insight, February 28, 2014 4:52 PM

ScienceDaily  |  Feb 20, 2014