PharmaMar's Investigational Drug PM1183 plus Doxorubicin Shows Remarkable Activity in Small Cell Lung Cancer

“PharmaMar today announced data from a Phase 1b study of the transcriptional inhibitor PM1183 in combination with doxorubicin in second line therapy in patients with small cell lung cancer (SCLC) showing that the treatment induced objective responses in 67% of the patients, including 10% of them where all signs of cancer disappeared (complete responses). Every patient with SCLC denominated primary chemotherapy-sensitive (their chemotherapy-free interval (CTFI) is more than 90 days) responded to treatment, including 18% of complete responses. In primary chemotherapy-resistant patients, where cancer was progressing within 90 days or less of previous chemotherapy, a remarkable 30% achieved a response. Notably, the treatment resulted in durable responses, with an overall progression-free survival (PFS) of 4.6 months, which was 3.6 months in resistant patients. The most common adverse drug reaction was reversible myelosuppresion but no cardiotoxicity or drug-related deaths were observed.

“ ‘The rate, depth and length of responses that we have observed with this treatment in the second-line setting are remarkable, even in those patients that are usually considered harder to treat”, said Dr. Martin Forster, University College Hospital, London, UK.

“ ‘Small cell lung cancer is an unmet clinical need with very few recent advances and the scientific community is committed to help new develop effective therapies.’ ”


Clovis Oncology's Rociletinib (CO-1686) Phase 2 Study Results Demonstrate Consistent and Promising Clinical Activity and Disease Control in Very Advanced Patients with EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC)

“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.’ “


Pfizer Drug Shows Early Promise in Xalkori-Resistant Lung Cancer-Study

“An experimental Pfizer Inc drug that aims to help lung cancer patients with specific genetic mutations who have stopped responding to the company’s Xalkori was showing promise in a small, early stage study, according to preliminary data revealed on Wednesday.

“The ongoing Phase I trial of the drug, PF-3922, was designed to determine if there is a maximum tolerable dose and which dose or doses to test in future larger trials.

“But researchers found some early evidence of efficacy, according to a brief summary of the study that will be presented at the upcoming American Society of Clinical Oncology (ASCO)meeting in Chicago later this month.

“Of 15 patients evaluated for efficacy, six, or 40 percent, had partial responses, meaning tumor shrinkage of at least 30 percent. Intracranial responses were observed in five patients, indicating that the drug had successfully crossed the blood/brain barrier to attack tumors in the brain, which are common in advanced, or metastatic, lung cancer.

” ‘There’s encouraging clinical activity despite that it’s an early study,’ said Ronit Simantov, head of medical affairs for Pfizer oncology.”


Clinical Trial of a New "panRAF" Inhibitor Enrolls First Melanoma Patient

“A patient has become the first to receive a new ‘resistance-busting’ experimental skin cancer drug with the launch of a phase I clinical trial.

“The patient has received a new panRAF inhibitor – a new type of drug under development to address the problem of drug resistance in advanced skin cancer and a number of other cancer types.

“The trial is the culmination of a pioneering research programme to design, synthesise and develop the new drug class, led by scientists at The Institute of Cancer Research, London, and the Cancer Research UK Manchester Institute at The University of Manchester.

“It is starting just three months after a major publication in the journal Cancer Cell described the potential of this new drug class, which is potentially able to treat melanomas – the most serious type of skin cancer – that do not respond or have become resistant to existing therapies.

“The phase I trial of the drug – which is yet to be given a formal name and is currently known as BAL3833/CCT3833 – is sponsored by The Institute of Cancer Research (ICR) and The Royal Marsden NHS Foundation Trust.”


Multiple Types of Resistance to New Lung Cancer Drug Identified

“After identifying three different types of resistance to a promising investigational lung cancer drug in a phase 1 trial, a team of researchers led by Dana-Farber Cancer Institute scientists say new targeted inhibitors and combinations are urgently needed to stay ahead of tumors’ constant and varied molecular shape-shifting.

“The researchers, including scientists from pharmaceutical company AstraZeneca, report in an advanced online publication in Nature Medicine on May 4, that their findings indicate ‘an underappreciated genomic heterogeneity’ in mechanisms of resistance to tyrosine kinase inhibitor (TKI) drugs that target the Epidermal Growth Factor Receptor (EGFR) mutation that drive some cases of non-small cell lung cancer (NSCLC).

” ‘If resistance that is this complex is constantly evolving before us, it may mean we need multiple targeted therapies in combination to stay ahead of the resistant cancer,’ said Geoffrey Oxnard, MD, a thoracic oncologist and lung cancer researcher at Dana-Farber and senior author of the report.”


Cabazitaxel May Be More Effective Than Docetaxel in Some Prostate Cancer Patients

“In a new study reported by de Leeuw et al in Clinical Cancer Research, researchers found that the novel taxane cabazitaxel (Jevtana) has properties that could make it more effective than docetaxel in some patients with advanced prostate cancer. This hypothesis is currently being tested in a phase II clinical trial. Researchers have also found a genomic marker that could help physicians identify which patients might benefit most from cabazitaxel.

“ ‘It was surprising to find that cabazitaxel functions differently than docetaxel in killing cancer cells, even though they’re both taxanes,’ said senior author  and Professor of Cancer Biology at the Sidney Kimmel Medical College at Thomas Jefferson University. ‘It shows that we may not be taking full advantage of this next-generation taxane in the clinic.’

“For years, docetaxel has been the only effective chemotherapy for men whose prostate cancer was no longer responding to hormone treatments. The next-generation drug in the taxane family, cabazitaxel, was approved by the U.S. Food and Drug Administration (FDA) in 2010, but only for patients whose prostate cancer no longer responded to hormone therapy or docetaxel treatment.

“Dr. Knudsen and colleagues explored how cabazitaxel worked and demonstrated that it might be more effective sooner in treatment. The researchers showed that cabazitaxel worked better than docetaxel in human prostate cancer cells lines that were resistant to hormone treatment, both in terms of slowing growth of cancer cells and in its ability to kill cancer cells.”


Novartis Lung Cancer Drug Zykadia® Recommended for EU Approval in Patients with ALK+ NSCLC Previously Treated with Crizotinib

“Novartis announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion for Zykadia® (ceritinib) to treat adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) previously treated with crizotinib[2]. If approved in the European Union (EU), Zykadia will be the first treatment option to address an unmet medical need for patients with ALK+ NSCLC previously treated with crizotinib.

” ‘Patients with advanced ALK+ NSCLC have few options when their cancer does not respond to currently approved therapy,’ said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. ‘As a leader in the development of precision oncology medicines, Novartis is committed to developing and bringing to market new treatments for patients with ALK+ NSCLC. This positive CHMP opinion for Zykadia brings us one step closer to providing the lung cancer community with new hope in the fight against this terrible disease.’

“Each year, there are 1.6 million people diagnosed with lung cancer, the leading cause of cancer death worldwide[3]. The most common type of lung cancer is NSCLC, accounting for 85-90% of all cases[4]. Of those, 2-7% are driven by a rearrangement of the ALK gene, which increases the growth of cancer cells and can be identified by a molecular test of the cancer tumor[1]. Despite significant treatment advances for patients with ALK+ NSCLC, disease progression is often inevitable and more treatment options are needed[5].”


Scientist Study Skin Cancer Patients Resistant to Leading Therapy

“Powerful drugs known as BRAF-inhibitors have been crucial for melanoma patients, saving lives through their ability to turn off the BRAF protein’s power to spur cancer cell growth.

“Yet they often work for only a year or less. Scientists know some of the DNA mutations that cause the drug resistance, but scientists have not been able to determine the underlying cause of the resistance in as many as a third of these patients. As a result, identifying genomic-based follow-up therapies for these patients has been a challenge.

“Researchers at The University of Texas MD Anderson Cancer Center may have found a way to more accurately predict which patients will likely respond to genomic-based follow-up therapies, by looking at unique ‘protein patterns’ in melanoma patients.

” ‘There are patients whose DNA does not reveal how their melanomas became resistant to BRAF inhibitors,’ said Lawrence Kwong, Ph.D., instructor in Genomic Medicine at MD Anderson. ‘So we looked at patterns of changes in 150 proteins which can give clues to the causes of resistance, even when DNA sequencing data is uninformative.’ “


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.”