On July 30, 2015 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported it has submitted the cobas EGFR Mutation Test v2 for Premarket Approval (PMA) to the U.S. Food and Drug Administration (FDA), as a companion diagnostic test for AZD9291, an AstraZeneca investigational therapy for non-small cell lung cancer patients with an acquired resistant mutation (Press release, Hoffmann-La Roche , JUL 30, 2015, View Source [SID:1234506754]).

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Patients with non-small cell lung cancer who have adenocarcinoma with tumor containing an EGFR sensitizing mutation show significant benefit from currently available EGFR TKI therapies. However, approximately two-thirds of these patients will relapse and develop drug resistance. In many cases, this resistance is caused by an acquired mutation called T790M. The cobas EGFR v2 test can aid clinicians to appropriately select NSCLC patients who have acquired the T790M mutation and are most likely to benefit from AstraZeneca’s novel therapy.

"The collaboration with AstraZeneca to be the companion diagnostic for their third generation EGFR drug therapy is a testament to the innovation and quality of Roche oncology assays and demonstrates the value of molecular testing in patients," said Paul Brown, Head of Roche Molecular Diagnostics (RMD). "At Roche Molecular Diagnostics, we have one of the broadest portfolios of FDA-approved tests for Oncology that enable clinicians to make informed treatment decisions for their patients."

"At AstraZeneca, we are focused on developing novel treatments that address the genetic drivers underlying lung cancer disease progression and resistance mechanisms. AZD9291 was designed to inhibit both the activating sensitising EGFRm and the resistance mutation, T790M. The partnership with Roche on developing a companion diagnostics test for AZD9291, ensures that physicians will be able to identify the patients most likely to benefit from the treatment," said Antoine Yver, Head of Oncology, Global Medicines Development at AstraZeneca.

About the cobas EGFR Mutation Test v2
The cobas EGFR Mutation Test v2 is built upon the existing FDA-approved cobas EGFR Mutation Test, developed by Roche. It is intended to identify a broad spectrum of EGFR mutations for patients with non-small cell lung cancer, including the T790M acquired resistant mutation.

About AZD9291
AZD9291 is a once daily, selective, irreversible EGFR TKI designed to target both the activating sensitising mutation, EGFRm, and T790M, the genetic mutation responsible for EGFR TKI treatment resistance in up to approximately two-thirds of cases of EGFRm advanced NSCLC. AZD9291 has been granted Breakthrough Therapy designation, Orphan Drug and Fast Track status by the US Food and Drug Administration (FDA).

On July 30, 2015 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that it has submitted applications to regulatory authorities in Japan, the United States and Europe (MHLW, FDA and EMA respectively) seeking an additional indication for its in-house developed anticancer agent Halaven (eribulin mesylate) as a treatment for soft tissue sarcoma (Press release, Eisai, JUL 30, 2015, View Source [SID:1234506753]).

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Halaven is the first and only single agent systemic therapy to demonstrate an improvement in overall survival (OS) in people previously treated for soft tissue sarcomas in a randomized controlled trial to date. In a Phase III clinical study (Study 309) which examined the efficacy and safety of Halaven versus dacarbazine in patients with locally advanced or recurrent and metastatic soft tissue sarcoma (one of two subtypes: leiomyosarcoma or adipocytic sarcoma) who had disease progression following standard therapies (including an anthracycline and at least one other additional regimen), Halaven demonstrated a statistically significant extension in the study’s primary endpoint of OS over the comparator treatment dacarbazine (Halaven median OS: 13.5 months vs dacarbazine median OS: 11.5 months, Hazard Ratio (HR) 0.768 [95% CI=0.618-0.954], p=0.017). In this study, the most common treatment-emergent adverse events observed in the Halaven arm were fatigue or asthenia, neutropenia, nausea, alopecia, and peripheral neuropathy, which was consistent with the known side-effect profile of Halaven.
These data were presented at an oral session at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in June 20151.

Soft tissue sarcoma is a collective term for a diverse group of malignant tumors that occur throughout the soft tissue (fat, muscle, nerves, fibrous tissues and blood vessels) in the body. Approximately 12,000 patients in the United States and 29,000 patients in Europe are diagnosed with soft tissue sarcoma each year. According to a patient survey conducted by the MHLW, there are approximately 4,000 patients with soft tissue sarcoma in Japan. Meanwhile, Halaven has been designated as an orphan drug for the treatment of soft tissue sarcoma in the United States and Japan.

Halaven is a halichondrin class microtubule dynamics inhibitor with a novel mechanism of action. It was first approved for the treatment of metastatic breast cancer in the United States in November 2010, and is currently approved in approximately 60 countries including Japan and countries in Europe, the Americas and Asia.
Eisai remains committed to providing further clinical evidence for Halaven aimed at maximizing value of the drug as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers.

< Notes to editors >

1. About Halaven (eribulin mesylate)
Halaven, a halichondrin class microtubule dynamics inhibitor with a novel mechanism of action, belongs to a class of antineoplastic agents, the halichondrins, which are natural products isolated from the marine sponge Halichondria okadai. It is believed to work by inhibiting the growth phase of microtubule dynamics without affecting the shortening phase and sequestering tubulin into nonproductive aggregates.
Halaven was first approved as a treatment for breast cancer in the United States in November 2010, and is now approved in nearly 60 countries worldwide, including Japan and countries in the Americas, Europe and Asia. In Japan, Halaven has been approved to treat inoperable or recurrent breast cancer and was launched in the country in July 2011. Halaven has also been approved in countries in Europe and Asia indicated as a treatment for patients with locally advanced or metastatic breast cancer who have progressed after at least one chemotherapeutic regimen for advanced disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting, unless patients were not suitable for these treatments. In addition, Halaven has been designated as an orphan drug for soft-tissue sarcoma in the United States and Japan.

2. About Soft Tissue Sarcoma
Soft tissue sarcoma is a collective term for a diverse group of malignant tumors that occur throughout the soft tissue (fat, muscle, nerves, fibrous tissues and blood vessels) in the body. As the structures where the tumors originate are diverse, there are various types of soft tissue sarcoma, and the most common types include leiomyosarcoma, adipocytic and malignant fibrous histiocytoma.
While treatment of soft tissue sarcoma is focused on curative surgery, if the degree of malignancy is high, treatment then becomes a combination of chemotherapy and radiation therapy. As outcomes are poor for patients with advanced disease, it remains a disease with significant unmet medical needs.

3. About Study 3091
Conducted primarily in Europe and the United States, Study 309 was a multicenter, open-label, randomized Phase III study comparing the efficacy and safety of Halaven versus dacarbazine in 452 patients (aged 18 or over) with locally advanced or recurrent and metastatic soft tissue sarcoma (one of two subtypes: leiomyosarcoma or adipocytic sarcoma) who had disease progression following standard therapies which must have included an anthracycline and at least one other additional regimen. Patients received either Halaven (1.4 mg/m2 administered intravenously on Day 1 and Day 8) or dacarbazine (850–1200 mg/m2 administered intravenously on Day 1) every 21 days until disease progression.
From the results for the study, Halaven demonstrated a statistically significant extension in the study’s primary endpoint of overall survival (OS) over the comparator treatment dacarbazine (Halaven median OS: 13.5 months vs dacarbazine median OS: 11.5 months, Hazard Ratio (HR) 0.768 [95% CI=0.618-0.954], p=0.017). Furthermore, in the study’s secondary endpoint of progression-free rate at 12 weeks (PFR12wks), while there was a numerical difference in PFR12wks between the Halaven and dacarbazine arms (33% vs 29%), this was not statistically significant. Median progression-free survival was 2.6 months in both arms.
In this study, the most common treatment-emergent adverse events observed in the Halaven arm were fatigue or asthenia, neutropenia, nausea, alopecia, and peripheral neuropathy, which was consistent with the known side-effect profile of Halaven.