Video: Dr. Joanne Blum on the Function of Talazoparib in Locally Advanced and/or Metastatic Breast Cancer

“Joanne Blum, MD, PhD, breast medical oncologist, director, Hereditary Cancer Risk Program, Baylor Charles A. Sammons Cancer Center, discusses the function of the oral PARP inhibitor talazoparib (BMN 673) in BRCA mutation subjects with locally advanced and/or metastatic breast cancer. Blum says the BRCA mutation works in combination with talazoparib in order to better cut off the appropriate pathways for the tumors.

“Blum said during the phase I trial that looked at talazoparib, patients experienced grade 1 neutropenia, cytopenia and fatigue. Blum added that the toxicities were very mild.”

Click through to watch the video.


Sarah Cannon Research UK and BioMarin Collaborate on EMBRACA Clinical Study in Hereditary Breast Cancer With BRCA Mutation

The gist: Researchers are conducting a clinical trial with volunteer patients to test a new breast cancer treatment called BMN673. BMN673 is a “PARP inhibitor” drug that may benefit patients who have hereditary mutations in the BRCA genes. Patients involved in the trial must have locally advanced and/or metastatic breast cancer, and must have undergone no more than two prior chemotherapy treatments for metastatic disease.

” ‘We are excited to collaborate with BioMarin on this landmark trial to increase the treatment opportunities for patients with BRCA related breast cancer,’ said Dr Alison Jones, Consultant Medical Oncologist and Principal Investigator for the EMBRACA Phase 3 trial at Sarah Cannon Research Institute UK.

” ‘This study is an important milestone for both organizations to foster future collaborations,’ highlighted Dr Hendrik-Tobias Arkenau, FRCP, PhD, Medical Oncologist and Medical Director at Sarah Cannon Research Institute UK.

” ‘Sarah Cannon Research UK has a long history of pioneering significant advances in medical therapy, and we are thrilled to commence enrollment outside of the United States to evaluate the safety and efficacy of BMN 673 in patients with hereditary breast cancer,’ said Hank Fuchs, M.D., Chief Medical Officer of BioMarin. ‘Breast cancer patients with germline BRCA-associated tumors have no targeted treatment options. There is an unmet need for therapies that target specific molecular defects in tumors, and PARP inhibitors offer that potential in BRCA-related breast cancer.’

“The EMBRACA Phse 3 study began in the United states in the fall of 2013 and has expanded internationally. BioMarin plans to enroll patients from sites around the world and to work with partners outside of the United States. The EMBRACA Phase 3 study is an open-label, randomized, parallel, two-arm, multi-center study of BMN 673 versus physician’s choice in approximately 430 germline BRCA mutation patients with locally advanced and/or metastatic breast cancer, who have received no more than two prior chemotherapy regimens for metastatic disease. The primary objective of the study is to measure progression free survival (PFS). Secondary objectives include evaluating the objective response rate (ORR) and the overall survival (OS).”


New Prospects for Small Cell Lung Cancer Patients (Part I)


Small cell lung carcinoma (SCLC) accounts for about 15% of lung cancers, but it is the deadliest form of lung malignancy. Only 6% of patients with SCLC survive beyond 5 years after diagnosis. In the last few years, new therapies—targeted therapies in particular—have been developed and approved by the U.S. Food and Drug Administration (FDA) for treating other, more common forms of lung cancer such as adenocarcinoma. However, not much progress has been made in addressing SCLC, which is usually treated with a combination of fairly toxic chemotherapeutics and radiotherapy. Many patients respond to these harsh treatments (ie, their tumors shrink), but only transiently. The disease recurs within a few months to 1 year and, at that point, is no longer treatable. Continue reading…


Proteomic Markers of DNA Repair and PI3K Pathway Activation Predict Response to the PARP Inhibitor BMN 673 in Small Cell Lung Cancer

 Here, we evaluate activity of a novel, potent PARP inhibitor, BMN 673, and identify markers of response as a basis for developing predictive markers for clinical application.

Elevated expression of multiple DNA repair proteins, as well as a corresponding “DNA repair protein score,” predict response to BMN 673 in in vitro SCLC models. These observations complement recent work in which PI3K inhibition sensitizes breast cancer models to PARP inhibition, suggesting cooperation between DNA repair and PI3K pathways.


BMN 673, a Novel and Highly Potent PARP1/2 Inhibitor for the Treatment of Human Cancers with DNA Repair Deficiency

PARP1/2 inhibitors are a class of anticancer agents that target tumor-specific defects in DNA repair. Here, we describe BMN 673, a novel, highly potent PARP1/2 inhibitor with favorable metabolic stability, oral bioavailability, and pharmacokinetic properties. BMN 673 is currently in early-phase clinical development.


BMN 673, a Novel and Highly Potent PARP1/2 Inhibitor for the Treatment of Human Cancers with DNA Repair Deficiency

“Purpose: PARP1/2 inhibitors are a class of anticancer agents that target tumor-specific defects in DNA repair. Here, we describe BMN 673, a novel, highly potent PARP1/2 inhibitor with favorable metabolic stability, oral bioavailability, and pharmacokinetic properties. Experimental Design: Potency and selectivity of BMN 673 was determined by biochemical assays. Anticancer activity either as a single-agent or in combination with other antitumor agents was evaluated both in vitro and in xenograft cancer models…Conclusion: BMN 673 is currently in early-phase clinical development and represents a promising PARP1/2 inhibitor with potentially advantageous features in its drug class.


Breast Cancer Drugs May Also Be Effective Against Some Lung Cancers

A class of drugs already in clinical trials for breast and ovarian cancer, so-called PARP inhibitors, may also be effective against some forms of non-small cell lung cancer (NSCLC). Around half of all NSCLC tumors have low levels of ERCC1, a protein that helps repair damaged DNA. PARP inhibitors act by blocking a different DNA repair mechanism. This creates a one-two punch that kills the NSCLC tumor cells that are low in ERCC1, while healthy cells remain relatively unharmed. A recent cell culture study showed that PARP inhibitors like olaparib, niraparib, and BMN 673 killed ERCC1-deficient NSCLC cells, but not cells with normal ERCC1 levels.


Promise for BRCA-Defective Cancers

“Germline mutations of either BRCA1 or BRAC2 are particularly associated with an increased risk for breast and ovarian cancer. The initial results of a Phase I/II trial reported at the annual meeting of the American Society of Clinical Oncology indicate that a new drug, BMN-673, developed by BioMarin Pharmaceuticals in…”


Promise for BRCA-Defective Cancers

“Germline mutations of either BRCA1 or BRAC2 are particularly associated with an increased risk for breast and ovarian cancer. The initial results of a Phase I/II trial reported at the annual meeting of the American Society of Clinical Oncology indicate that a new drug, BMN-673, developed by BioMarin Pharmaceuticals in…”