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Ganymed Pharmaceuticals Announces CE Marking for Test to Assess Claudin-18.2 Expression in Solid Tumors

Ganymed Pharmaceuticals announced today that it has fully developed and obtained CE marking for its in vitro diagnostic (IVD) test CLAUDETECTTM18.2 which allows to assess the expression levels of Claudin-18.2 (CLDN18.2) in solid tumors. CLAUDETECTTM18.2, which was developed in collaboration with Theracode GmbH, is now compliant with the requirements of European Community Directive 98/79/EC on in vitro diagnostic medical devices.

Mayo Clinic Researchers Identify Biomarker for Smoker’s Lung Cancer

Mayo Clinic researchers have shown that a specific protein pair may be a successful prognostic biomarker for identifying smoking-related lung cancers. The protein — ASCL1 — is associated with increased expression of the RET oncogene, a particular cancer-causing gene called RET. The findings appear in the online issue of the journal Oncogene.

“This is exciting because we’ve found what we believe to be a ‘drugable target’ here,” says George Vasmatzis, Ph.D., a Mayo Clinic molecular medicine researcher and senior author on the study. “It’s a clear biomarker for aggressive adenocarcinomas. These are the fast-growing cancer cells found in smokers’ lungs.”

ASCL1 is known to control neuroendocrine cell development and was previously linked to regulation of thyroid and small cell lung cancer development, but not smoking-related lung cancer. The research also showed that patients with ASCL1 tumors with high levels of the RET oncogene protein did not survive as long as ASCL1 patients with low levels of RET.

When researchers blocked the ASCL1 protein in lung cancer cell lines expressing both genes, the level of RET decreased and tumor growth slowed. This leads researchers to believe this mechanism will be a promising target for potential drugs and a strong candidate for clinical trials.

The co-authors of the study include Farhad Kosari, Ph.D.; Cristiane Ida, M.D.; Marie Christine Aubry, M.D.; Lin Yang, Ph.D.; Irina Kovtun, Ph.D.; Janet Schaefer Klein; Yan Li, M.D.; Sibel Erdogan; Sandra Tomaszek, M.D.; Stephen Murphy, Ph.D.; Lynn Bolette; Christopher Kolbert; Ping Yang, M.D., Ph.D.; and Dennis Wigle, M.D., Ph.D., all of Mayo Clinic.

The research was supported by a Waterman Biomarker Discovery grant and by the Mayo Clinic Center for Individualized Medicine.

Study: ASCL1 and RET expression defines a clinically relevant subgroup of lung adenocarcinoma characterized by neuroendocrine differentiation [Oncogene]

Source: Mayo Clinic

MolecularMD Corp. Obtains License to Commercialize Predictive Diagnostic Based on Actionable Biomarker, DDR2, for Uses in Lung Cancer and Targeted Kinase Therapy

MolecularMD Corp. recently announced that it has entered into a license agreement granting the company exclusive patent rights to cancer diagnosis technology. Specifically, MolecularMD has obtained rights to commercialize patent-pending intellectual property pertaining to DDR2 mutations for diagnostic, prognostic and predictive uses for humans in the area of lung cancer. Such patent rights are jointly-owned by The Broad Institute and Dana-Farber Cancer Institute. The inventors named on the patent are Drs. Matthew Meyerson, Peter Hammerman, and Alexis Ramos.

About DDR2 Mutations in Lung Cancer

Research into understanding the genetic basis of cancer has led to identification of novel biomarkers that have been successfully exploited with targeted therapies. In non-small cell lung cancer (NSCLC), several such targets have been discovered for adenocarcinoma including EGFR, ALK, and MET. Unfortunately, these therapeutic targets are not relevant for squamous cell carcinoma (SCC), which is the second most frequent histological subtype in NSCLC. Recent discoveries identified mutations in the discoidin domain receptor 2 (DDR2) of SCC patient tumors that are oncogenic and also responsive to existing drugs targeting kinase inhibition. DDR2 is a membrane receptor tyrosine kinase involved in cell adhesion, proliferation and migration. In xenograft models, DDR2-mutant tumors regressed under treatment with the tyrosine kinase inhibitor, dasatinib. Remarkably, an SCC patient with no detectable EGFR mutation had a long-term response to the combination of erlotinib plus dasatinib. This patient was found to harbor a DDR2 mutation further suggesting that DDR2 mutations may be clinically relevant. Given the availability of a variety of therapies targeting tyrosine kinases, these findings provide a rationale for designing clinical trials for patients with SCC using existing FDA-approved drugs such as dasatinib, imatinib, nilotinib and ponatinib as well as novel, selective tyrosine kinase inhibitors for DDR2.

MolecularMD is developing DDR2 diagnostic assays, including next-generation sequencing tests, for clinical trials exploring efficacy of targeted therapies and DDR2 clinical utility. MolecularMD provides comprehensive clinical trial support through its CLIA-certified and CAP-accredited Clinical Reference Laboratory. In addition, MolecularMD provides IVD development and manufacturing capability to support companion diagnostic device commercialization. MolecularMD will also support commercialization of DDR2 technology through sublicensing to clinical reference laboratories and diagnostic assay developers and manufacturers.

According to Dr. Greg Cox, MolecularMD’s Director of Licensing, “DDR2 is potentially the first actionable biomarker available for SCC patients, whose treatment options are currently limited to chemotherapy. It’s exciting that these patients may benefit from existing FDA-approved targeted therapies, and we are eager to support clinical trials examining these novel treatment possibilities and enable widespread access to DDR2 diagnostics.”

U.S. FDA Approves Gilotrif (afatinib) as First-line Treatment for Lung Cancer Patients with EGFR Mutations

Boehringer Ingelheim announced last week that the U.S. Food and Drug Administration (FDA) has approved afatinib tablets under the U.S. brand name GILOTRIFTM for oral use, as a new first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) whose tumours have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test.

Lung cancer is the biggest cancer killer in the world with incidence rates higher in men than in women, it accounts for 1.6 million new cancer cases annually. However, lung cancer isn’t just one disease; research has shown there are many different types requiring specific treatment approaches. One distinct subtype of lung cancer is defined by mutations in EGFR (a member of the ErbB Family of receptors). These are patients that in clinical trials have been shown to benefit most from afatinib treatment.

“We are delighted to announce the first approval of afatinib, offering a new personalised treatment approach for patients with EGFR mutation positive NSCLC,” said Prof Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. “It marks the first of what we hope will be many products to emerge from our oncology research and development programme, and underscores our continued commitment to translating innovative science into new treatment options for patients.”

In the U.S., afatinib received orphan drug status and was assessed under the FDA’s priority review programme, which provides an expedited review for drugs that may provide safe and effective therapy when no satisfactory alternative therapy exists, or offer significant improvement compared to marketed products. Boehringer Ingelheim strives to make afatinib available to patients around the world. Afatinib has been submitted to the EMA and regulatory authorities in Asia and other countries for treatment of EGFR mutation positive locally advanced and metastatic NSCLC.

The approval of afatinib in the U.S. is based on data from the pivotal LUX-Lung 3 trial, comparing afatinib to chemotherapy with pemetrexed/cisplatin. Data from LUX-Lung 3 has shown that patients taking afatinib as a first-line treatment lived for almost one year without their tumour growing again (median progression-free survival (PFS) of 11.1 months) versus just over half a year (PFS of 6.9 months) for those treated with pemetrexed/cisplatin. In addition, NSCLC patients with tumours harbouring the two most common EGFR mutations (Del19 or L858R) taking afatinib lived for well over a year without tumour progression (PFS of 13.6 months) versus just over half a year (PFS of 6.9 months) for those in the comparator arm.

In addition, patients taking afatinib also experienced an improvement in lung cancer symptoms and a better quality of life compared to those receiving standard chemotherapy treatment.

The most common grade 3 drug-related adverse events observed in the afatinib treatment arm were diarrhoea (14%), rash (16%), and inflammation of the nail bed (paronychia) (11%). The most common drug-related grade 3 adverse events observed in the chemotherapy arm (pemetrexed/cisplatin) were neutropenia (15%), fatigue (13%), and leucopenia (8%). There was a low discontinuation rate associated with treatment-related adverse events in the trial (8% discontinuation rate for afatinib; 12% for chemotherapy). One percent of patients in the afatinib arm discontinued due to drug-related diarrhoea.

Study: Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations

Source: Boehringer Ingelheim

Pretesting Cervical Tumors Could Inform Treatment

Doctors at Washington University School of Medicine in St. Louis have shown that testing cervical tumors before treatment for vulnerability to chemotherapy predicts whether patients will do well or poorly with standard treatment. The study supports the future possibility of personalized medicine for cervical cancer, a tumor normally addressed with a one-size-fits-all approach.

“Even though this is a small study, its strength is that it links a lab test of the tumor’s chemotherapy response to survival outcomes for the patients,” said Julie K. Schwarz, MD, PhD, assistant professor of radiation oncology. “Very few cancers have been studied this way, and this is the first such report for cervical cancer.”

Since 1999, nearly all cervical cancer cases have been treated the same way: daily radiation therapy targeted to the tumor plus a weekly intravenous infusion of the chemotherapy drug cisplatin.

“We believe that radiation does the majority of the work with cervical cancer,” said Schwarz, who treats patients at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. “But a randomized trial published in 1999 showed that combining it with cisplatin chemotherapy improved survival outcomes.”

Even today, according to Schwarz, doctors have no way of knowing who will do well or poorly with the combined radiation and chemotherapy that every patient receives. Now, Schwarz and her colleagues have shown that the tumor’s response to chemotherapy, independent of radiation, may be a major deciding factor in whether a patient will do well with the standard treatment.

The study appears online in the journal Gynecologic Oncology.

“This is evidence that cisplatin is not just helping the radiation work better,” Schwarz said. “It is having some direct toxic effect on cancer cells that may be hiding elsewhere in the body, some place where the radiation is not hitting it, since we target the radiation so precisely to the main tumor. We think it would be beneficial for that drug to be selected appropriately for the patient’s individual tumor.”

The investigators tested tumors from 33 cervical cancer patients before their treatment began. They divided the patients’ tumors into three categories – responsive, intermediate response and nonresponsive – based on how well cisplatin killed the tumor cells growing in a dish.

For tumors categorized as responsive – those cancer cells that cisplatin killed most easily – 100 percent of the patients were alive and disease-free after two years. For those that showed an intermediate response, 83 percent of the patients were alive and disease-free after two years. And for those tumors deemed nonresponsive, only 58 percent of patients had two-year disease-free survival.

Cervical cancers can be divided into two main types based on how they look under a microscope – squamous cell carcinoma and adenocarcinoma. The nonresponsive number was even worse for patients diagnosed with the more common squamous cell carcinoma, with 46 percent disease-free survival at two years.

“Ideally, we would like to be able to design clinical trials for the nonresponsive patients,” Schwarz said. “One chemotherapy drug isn’t working for everyone, but there isn’t going to be one explanation for why the chemo doesn’t work. It’s going to be 50 different explanations, and figuring that out is the challenge.”

Schwarz is quick to point out the weaknesses of this study. In addition to the small number of patients, the lab test used was not ideal and should not be used to decide therapy for patients, she said. The investigators initially evaluated 75 tumors for chemotherapy response. And though some patients’ data was not included because they did not adhere to the treatment regimen, 31 patients were excluded from the analysis because their tumor cells did not grow well in the lab.

“This is definitely not the definitive test,” Schwarz said. “But I think our results should prompt investigators to think outside the box and start generating new ideas about how best to treat this disease. The bottom line is a one-size-fits-all treatment for each patient is going by the wayside. As we develop personalized strategies, this is the sort of testing that can guide it.”

Study: In vitro chemoresponse to cisplatin and outcomes in cervical cancer.

Source: Washington University in St. Louis