On February 12, 2016 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that the U.S. Food and Drug Administration (FDA) has scheduled the New Drug Application (NDA) for rociletinib for discussion by the Oncologic Drugs Advisory Committee (ODAC) on April 12, 2016 (Press release, Clovis Oncology, FEB 12, 2016, View Source [SID:1234509053]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Rociletinib is an investigational therapy for the treatment of patients with mutant epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) who have been previously treated with an EGFR-targeted therapy and have the EGFR T790M mutation.

The ODAC reviews and evaluates data concerning the safety and effectiveness of marketed and investigational human drug products for use in the treatment of cancer and makes recommendations to the FDA.

"We are actively preparing for this advisory committee meeting and look forward to the discussion about rociletinib," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "New treatments are needed for this hard-to-treat patient population, and we believe that rociletinib represents an important new option for patients with mutant EGFR T790M-positive lung cancer."

About Rociletinib

Rociletinib is the company’s novel, oral, targeted covalent (irreversible) mutant-selective inhibitor of EGFR in development for the treatment of NSCLC in patients with initial activating EGFR mutations, as well as the dominant resistance mutation T790M. Data from both the pivotal, single-arm TIGER-X and TIGER-2 clinical trials served as the basis for the U.S. and EU regulatory submissions for the treatment of advanced mutant EGFR T790M-positive lung cancer. Rociletinib was granted Breakthrough Therapy designation by the FDA in May 2014.

On February 12, 2016 Celsion Corporation (Celsion) (NASDAQ: CLSN), a fully-integrated oncology company focused on the development of a portfolio of innovative cancer treatments, reported recent accomplishments related to the Company’s GEN-1 immunotherapy pipeline and provided a general business update (Press release, Celsion, FEB 12, 2016, View Source [SID:1234509051]). Celsion also announced the completion of enrollment of the first cohort of patients in its Phase 1b dose escalating clinical trial (the OVATION Study) combining GEN-1, the Company’s DNA-based immunotherapy, with the standard of care for the treatment of newly-diagnosed ovarian cancer patients who will undergo neoadjuvant chemotherapy followed by surgical resection of their tumor.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"GEN-1 is designed to locally activate IL-12 production using our novel targeted non-viral delivery platform for a sustained period for up to 7 days in the tumor environment," stated Dr. Nicolas Borys, Celsion’s senior vice president and chief medical officer. "Emerging preclinical and translational data demonstrate that GEN-1 stimulates the local cellular production and secretion of highly-tolerable endogenous IL-12, a potent multi-mechanistic anti-cancer agent, while limiting toxicities, poor tolerability, and poor pharmacokinetics associated with systemically administered recombinant IL-12."

The OVATION Study

The first two patients in the OVATION Study who completed treatment have shown promising results. Both patients reported stable disease with a dramatic drop in their CA-125 protein levels of 89% and 98%. Cancer antigen 125 (CA-125) is used to monitor certain cancers during and after treatment. CA-125 is present in greater concentrations in ovarian cancer cells than in other cells. A 50% reduction in CA-125 levels is considered meaningful. Both patients’ CA-125 levels were below the normal healthy level of 35 U/mL. In addition, both patients experienced successful surgical resections of their tumors with one patient reporting a R0 resection which indicates a microscopically margin-negative resection in which no gross or microscopic tumor remains in the tumor bed.

The OVATION Study will continue into 2016 at higher doses of GEN-1 with the goal to identify a safe, tolerable and therapeutically active dose of GEN-1 by recruiting and maximizing an immune response. Celsion has initiated four clinical sites at the University of Alabama at Birmingham; Oklahoma University Medical Center; Washington University in St. Louis and the Medical College of Wisconsin. The trial is designed to enroll three to six patients per dose cohort and will evaluate safety and efficacy and attempt to define an optimal dose for a follow-on Phase I/II study combining GEN-1 with Avastin and Doxil.

GEN-1 + Avastin + Doxil Program

The Company has completed various preclinical studies combining GEN-1 with Avastin and Doxil, the current standard of care for the treatment of platinum resistant ovarian cancer, which has demonstrated synergistic anti-cancer effects. The Company’s preclinical data abstract summarizing these studies has been accepted for presentation at the upcoming AACR (Free AACR Whitepaper) Annual Meeting 2016 in New Orleans. Data from these studies will be used to support an IND filing for a Phase I/II clinical trial evaluating the combination in recurrent ovarian cancer later this year.

Supporting Translational Data

In January 2016, the Company reported translational research data from its recently completed Phase 1b Study of GEN-1 in combination with PEGylated doxorubicin (Doxil) in patients with platinum-resistant ovarian cancer. This important data provides evidence that intraperitoneally-administered GEN-1 produces an immunologically distinct IL-12 protein that is localized at the tumor site and lasts for up to one week after a single treatment. Furthermore, concomitant increases in IFN-γ and TNF- α indicate that the IL-12 produced following treatment with GEN-1 treatment is immunologically active.

In addition to this strongly supportive translational data, GEN-1 has demonstrated encouraging safety and efficacy data in this Phase 1b trial in combination with Doxil as summarized below:

Findings from this trial demonstrated an overall clinical benefit of 57.1% for all treatment arms, with a partial response (PR) rate of 21.4% and a stable disease (SD) rate of 35.7%
There was a 100% overall clinical benefit observed at the highest dose cohort in this difficult-to-treat patient population (PR=33% and SD=67%) in all six evaluable patients
GEN-1 was well tolerated, with no dose limiting toxicities and no overlapping toxicities between GEN-1 and Doxil.
Business Update

The Company also reported a year-end cash position of $20.1 million (unaudited) compared to $24.1 million reported at the end of the third quarter of 2015.

"Celsion continues to make significant progress across our pipeline of directed chemotherapies, immunotherapies and RNA-based therapies, which we anticipate will position the company to achieve value-creating milestones in 2016," said Michael H. Tardugno, chairman, president and CEO. "As we look toward 2016, we will continue to maintain tight controls over our spending with a sharp focus on those programs that will drive both near-term and long-term value for our shareholders."

About GEN-1 Immunotherapy

GEN-1, designed using the TheraPlas platform technology, is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system which enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anti-cancer immunity acting through the induction of T-lymphocyte and natural killer (NK) cell proliferation. The Company has previously reported positive safety and encouraging Phase I results with GEN-1 given as monotherapy in patients with peritoneally metastasized ovarian cancer and in combination with PEGylated doxorubicin in patients with platinum resistant ovarian cancer.

On February 12, 2016 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that the results of a Phase III clinical study (Study 309) of its in-house discovered and developed anticancer agent Halaven (eribulin mesylate) in patients with locally advanced, recurrent or metastatic soft tissue sarcoma (liposarcoma or leiomyosarcoma)1 have been published in the online version of The Lancet, a leading medical journal that is highly regarded worldwide (Press release, Eisai, FEB 12, 2016, View Source [SID:1234509044]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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. In Study 309, which examined the efficacy and safety of Halaven versus dacarbazine in patients with locally advanced, recurrent or metastatic soft tissue sarcoma (liposarcoma or leiomyosarcoma) 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) 0.77 [95% CI=0.62-0.95], p=0.0169).
In this study, the most common treatment-emergent adverse events (incidence greater than or equal to 25%) in patients treated with Halaven were fatigue, neutropenia, nausea, alopecia, constipation, peripheral neuropathy, abdominal pain, and pyrexia, which was consistent with the known side-effect profile of Halaven.

Halaven is a halichondrin class microtubule dynamics inhibitor with a novel mechanism of action. Recent non-clinical studies showed that Halaven is associated with increased vascular perfusion and permeability in tumor cores.2 Halaven promotes the epithelial state and decreases the capacity of breast cancer cells to migrate.3 It was first approved for the treatment of metastatic breast cancer in the United States in November 2010, and is currently approved for use in the treatment of breast cancer in approximately 60 countries including Japan and countries in Europe, the Americas and Asia.

In January 2016, Halaven was approved in the United States for the treatment of patients with unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen, and applications seeking approval for use in the treatment of soft tissue sarcoma are currently under review in Japan and Europe. Halaven has been designated as an orphan drug for the treatment of soft tissue sarcoma in the United States and Japan.

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.

1. About Halaven (eribulin mesylate)
Halaven is a halichondrin class microtubule dynamics inhibitor with a novel mechanism of action. Structurally Halaven is a simplified and synthetically produced version of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai. Halaven is believed to work by inhibiting the growth phase of microtubule dynamics which prevents cell division. In addition, recent non-clinical studies showed that Halaven is associated with increased vascular perfusion and permeability in tumor cores.2 Halaven promotes the epithelial state and decreases the capacity of breast cancer cells to migrate.3
Halaven was first approved as a treatment in the United States in November 2010 for patients with metastatic breast cancer who have received at least two chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting. Halaven is currently approved for use in the treatment of breast cancer in approximately 60 countries worldwide, including Japan and countries in Europe, Americas 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.
Regarding soft tissue sarcoma, Halaven has been approved in the United States for the treatment of patients with unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen, and applications seeking approval for use in the treatment of soft tissue sarcoma have been submitted in Japan and Europe. Halaven has been designated as an orphan drug for the treatment of 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, liposarcoma and malignant fibrous histiocytoma. 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 Japan’s Ministry of Health, Labour and Welfare, there are approximately 4,000 patients with soft tissue sarcoma in Japan. 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 need.

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, recurrent or metastatic soft tissue sarcoma (liposarcoma or leiomyosarcoma) 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) 0.77 [95% CI=0.62-0.95], p=0.0169). 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.
The most common adverse reactions (incidence greater than or equal to 25%) in patients treated with Halaven were fatigue, neutropenia, nausea, alopecia, constipation, peripheral neuropathy, abdominal pain, and pyrexia, which was consistent with the known side-effect profile of Halaven.