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Nektar Presents Target-Specific Biomarkers Being Assessed in Ongoing Phase 3 BEACON Study of Etirinotecan Pegol for the Treatment of Metastatic Breast Cancer at the 2013 American Society of Clinical Oncology Annual Meeting

Nektar Therapeutics (NASDAQ:NKTR) recently announced that it presented a series of target-specific biomarkers that are being evaluated in the development of etirinotecan pegol for the treatment of breast cancer. Etirinotecan pegol is a unique, next generation, targeted topoisomerase I inhibitor currently in Phase 3 clinical development as a potential treatment for patients with locally recurrent or metastatic breast cancer. The BEACON (BrEAst Cancer Outcomes with NKTR-102) Phase 3 Study is a randomized, open-label, international study that is evaluating single agent etirinotecan pegol in patients who have previously received an anthracycline, a taxane and capecitabine (ATC) versus a comparator arm consisting of an active single agent treatment of physician’s choice (TPC).

“One of our objectives in treating metastatic breast cancer is to prospectively identify patients that will respond to specific treatments so they can achieve the optimal individualized care,” said Hope Rugo, M.D., Director of Breast Oncology and Clinical Trials Education at the UCSF Helen Diller Comprehensive Cancer Center and Member of the BEACON Study investigator steering committee. “The goal of evaluating these important biomarkers in patients enrolled into the BEACON study is to help us understand which breast cancer patients might have the best clinical outcomes from treatment with etirinotecan pegol.”

A series of assays for target-specific pharmacodynamic biomarkers for etirinotecan pegol, including the molecular target topoisomerase I, have been established and are being measured in the Phase 3 BEACON study. The biomarkers were identified from Circulating Tumor Cell (CTC) samples which were collected prior to patient treatment. Additional CTC patient samples are being collected at regular intervals during treatment and at the end of treatment. Preliminary results from the initial pre-dose samples found CTCs in over 90% of patient samples, with a median of 200 CTCs per 7.5 mL blood draw. Patient participation in the CTC sub-set of the BEACON study is projected to be over 75%. Measurements of each biomarker expression over time will be analyzed in order to identify potential predictive biomarkers for clinical response to etirinotecan pegol.

“We are pleased to have identified several baseline pharmacodynamic biomarkers, which are target-specific such as topoisomerase 1, and which can be reliably measured over the patient’s treatment period,” said Robert Medve, M.D., Chief Medical Officer of Nektar Therapeutics. “The measurement of these biomarkers in the BEACON study will help us understand and shape the future treatment of patients with etirinotecan pegol. Enrollment in the BEACON study is well ahead of schedule and we expect to complete the target enrollment of 840 patients in the third quarter of 2013.”

Circulating Tumor Cells are cancer cells shed from either the primary tumor or its metastases that circulate in the peripheral blood. CTCs are emerging tumor biomarkers, collected through a minimally invasive blood draw, providing a “liquid” biopsy sample and allowing for post-treatment monitoring of the patient. CTCs provide well-defined targets for the understanding of tumor biology and tumor cell dissemination, which offers a unique approach to identify novel therapeutic targets and understand resistance to established therapies.

Source: Nektar Therapeutics

Biomarker Analysis Identified Women Most Likely to Benefit From T-DM1

For women with metastatic, HER2-positive breast cancer, the amount of HER2 on their tumor might determine how much they benefit from a drug called trastuzumab emtansine (T-DM1), according to data from a subanalysis of the phase III clinical trial that led the U.S. Food and Drug Administration to approve the drug on Feb. 22, 2013. These findings were presented by José Baselga, M.D., Ph.D., physician-in-chief at Memorial Sloan-Kettering Cancer Center in New York, N.Y., at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“EMILIA was a landmark phase III clinical trial,” said Baselga. “It showed that T-DM1 prolonged progression-free and overall survival for patients with HER2-positive metastatic breast cancer that had been previously treated with trastuzumab and a taxane chemotherapy compared with lapatinib plus capecitabine. Also, it provided proof-of-concept that a new class of drugs called antibody-drug conjugates can benefit patients.”

Antibody-drug conjugates consist of an antibody attached to a toxic chemotherapy, according to Baselga. In the case of T-DM1, the antibody is trastuzumab and the toxic chemotherapy is emtansine. Trastuzumab recognizes the protein HER2, which is found at high levels in HER2-positive breast cancers, and targets the emtansine to the HER2-positive cancer cells, which are killed by the toxic chemotherapy.

In this subanalysis, Baselga and colleagues analyzed tissue samples from patients enrolled in EMILIA to examine whether tumor levels of HER2, as assessed by the amount of HER2 messenger ribonucleic acid (mRNA), affected treatment response. Patients with tumor samples expressing greater than the median amount of tumor HER2 mRNA were considered to have high levels of HER2. Those with tumor samples expressing the median amount of tumor HER2 mRNA or less were considered to have low levels of HER2.

“Even though everyone enrolled in the clinical trial had breast cancer expressing elevated levels of HER2, we know that each person’s tumor has different molecular features,” said Baselga. “Even the degree to which HER2 expression is elevated differs from patient to patient.”

Consistent with the prior analysis, he and his colleagues found that all patients treated with T-DM1 had significantly longer progression-free and overall survival compared with those treated with lapatinib and capecitabine (9.6 months progression-free survival versus 6.4 months; and 30.9 months for overall survival versus 25.1 months).

Patients with tumors expressing higher levels of HER2 derived greater benefit from treatment with T-DM1 compared with patients with tumors expressing lower levels of HER2: Overall survival was 34.1 months for those with high levels of HER2 versus 26.5 months. For patients with tumors expressing higher levels of HER2, those receiving T-DM1 had a 47 percent decreased risk for death compared with those receiving lapatinib and capecitabine.

The researchers also investigated whether tumor mutations in the PIK3CA gene affected treatment response. According to Baselga, patients with PIK3CA-mutated, HER2-positive breast cancer normally do not respond as well to treatment with conventional HER2-targeted therapies such as trastuzumab compared with patients without PIK3CA mutations in their tumors.

However, for patients treated with T-DM1, PIK3CA mutation status did not significantly decrease progression-free survival.

“Our findings are an important step toward identifying the best therapy for individual patients with HER2-positive breast cancer,” said Baselga. “HER2-positive breast cancer is not a uniform disease; each patient is different. These data help us as we look to identify a panel of molecular features that we can use to make informed treatment decisions.”

Kadcyla (ado-trastuzumab emtansine or T-DM1) is a trademark of Genentech, a member of the Roche Group.

Source: American Association for Cancer Research

Early Economic Evaluation Highlights the Potential Benefits of Biomarker-Directed Care in Breast Cancer and Renal Cell Carcinoma

GE Healthcare today announced results of three health economic models to estimate the potential cost offsets to the healthcare system of biomarker testing in patients with early breast cancer, metastatic breast cancer and renal cell carcinoma to guide therapy selection. These studies were presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 15th European Congress in Berlin, Germany.

Saladax Biomedical, Inc. Extends Availability of its MyCare Portfolio in Europe

Saladax Biomedical, Inc., a privately held company developing and commercializing novel diagnostic assays to achieve the promise of personalized medicine for new and existing therapeutics, recently announced the company has achieved CE mark registration for its MyPaclitaxel and MyDocetaxel therapeutic dose management (TDM) MyCare assays, enabling commercialization in the European Union (EU).

Clarient Receives Patents for Taxane Biomarker

Clarient, Inc., a premier technology and services resource for pathologists, oncologists and the pharmaceutical industry, today announced that the United Kingdom Patent Office has granted a U.K. patent on the Company’s TLE3 biomarker, a marker which may be used to predict which cancer patients will respond favorably to taxane therapy. In addition, the Company has received a Notice of Allowance from the United States Patent and Trademark Office (USPTO) for a U.S. patent on the TLE3 biomarker. Other patents for the TLE3 biomarker are pending in the U.S., Canada, Japan, China, India and elsewhere in Europe.