On March 26, 2015 Eisai reported that it has received manufacturing and marketing authorization in Japan for its in-house developed novel anticancer agent Lenvima (lenvatinib mesylate) indicated for the treatment of unresectable thyroid cancer (Press release, Eisai, MAR 26, 2015, View Source [SID:1234502553]).

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In a global Phase III study (the SELECT study) of Lenvima in differentiated thyroid cancer, Lenvima demonstrated a statistically significant extension in progression free survival and improved response rates compared to placebo1. In the SELECT study, the five most common Lenvima treatment-related adverse events of any grade were hypertension, diarrhea, fatigue or asthenia, decreased appetite, and weight loss. Furthermore, a Phase II study (Study 208) conducted in Japan suggested efficacy and tolerability of Lenvima in medullary thyroid carcinoma and anaplastic thyroid carcinoma as well2. Due to the results of these studies, Lenvima is the first molecular targeted treatment in Japan approved with an indication for unresectable thyroid cancer which covers differentiated thyroid cancer as well as medullary thyroid carcinoma and anaplastic thyroid carcinoma.

The number of patients with thyroid cancer in Japan is estimated to be between 13,000 and 29,000. Although treatment is possible for most types of thyroid cancer, there are few treatment options available for unresectable thyroid cancer and so there is a pressing need for the development of new treatment options. With a high degree of clinical malignancy and a prognosis among the worst of all types of cancer, anaplastic thyroid carcinoma in particular is a disease with significant unmet medical needs. Through this approval, Eisai hopes that Lenvima will make a contribution to patients as a new standard treatment for unresectable thyroid cancer, which has no established standard treatment in Japan at present.

Lenvima is an orally administered molecular targeted agent that selectively inhibits the activities of several different molecules including VEGFR, FGFR, RET, KIT and PDGFR. In particular, the agent simultaneously inhibits VEGFR, FGFR and also RET which are especially involved in tumor angiogenesis and proliferation of thyroid cancer. Furthermore, Lenvima has been confirmed through X-ray co-crystal structural analysis to demonstrate a new binding mode (Type V) to VEGFR2, and exhibits rapid binding to the target molecule and potent inhibition of kinase activity, according to kinetic analysis3.

Lenvima was launched in the United States indicated for the treatment of locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer in February 2015. Currently, the agent is undergoing regulatory review in the EU, as well as Switzerland, South Korea, Canada, Singapore, Russia, Australia and Brazil. Furthermore, Eisai is conducting a global Phase III trial of Lenvima in hepatocellular carcinoma as well as Phase II studies of Lenvima in several other tumor types such as renal cell carcinoma and non-small cell lung cancer. Eisai Co., Ltd. No.15-20 March 26, 2015 In addition to providing Lenvima as a new treatment option for thyroid cancer, in accordance with the conditions of approval, Eisai will work after launch to carry out an observational study and promote the appropriate use of Lenvima. Eisai is committed to exploring the potential clinical benefits of Lenvima in order to further contribute to patients with cancer, and their families.

On March 25, 2015 Cellular Biomedicine Group reported clinical data from its CAR-T immuno-oncology clinical development programs (Press release, Cellular Biomedicine Group, MAR 25, 2015, View Source [SID:1234502522]). The data will be discussed by Dr. Wei (William) Cao, PhD, BM, Chief Executive Officer of Cellular Biomedicine Group, at the 2015 Annual Regen Med Investor Day on March 25 in New York City .

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Dr. Cao commented, "We are very pleased with the efficacy and toxicity profile of our CAR-T technology, given the advanced stage of the cancer patients in the trials. With over 3.5 million new cancer patients diagnosed every year in China, developing safer and more effective cancer immunotherapy programs with leading hospitals will serve urgent unmet medical needs. We look forward to additional progress in advancing our CAR-T cell pipeline with further clinical development of our CD19, CD20, CD30 and EGFR-HER1 constructs."

About the Trials

The CAR-T trials were designed and conducted by Chinese PLA General Hospital ("PLAGH", Beijing, also known as "301 Hospital"), led by Principal Investigator Wei Dong Han, MD, PhD, head of PLAGH’s cancer immunotherapy department. They studied genetically engineered lymphocyte therapy in treating patients with B-cell leukemia or lymphoma that is relapsed (after stem cell transplantation or intensive chemotherapy) or refractory to available therapeutics. The studies recruited male and female subjects with CD19+ and CD20+ B cell malignancies with no available curative treatment options (such as autologous or allogeneic SCT) that had limited prognosis (several months to < 2 year survival) with currently available therapies.

CAR-T CD19 for Acute Lymphocytic Leukemia (B-cell ALL) Data Analysis

Nine adult patients with relapsed or chemotherapy-refractory B-cell lineage acute lymphocytic leukemia (B-cell ALL) were enrolled in this CAR-CD19 T cell therapy trial. Results showed a complete response (CR) rate of 22.2% (two out of nine patients) and a partial response (PR) rate of 44.4% (four out of nine patients) for an overall response rate (ORR) of 66.7% (six out of nine patients). Further subgroup analysis showed an overall response rate (ORR) of 71.5% (five out of seven patients) in the six CD19 patients with extramedullary involvement and one patient with no extramedullary lesions and treated with autologous CAR-CD19 T cell therapy. In the six CD19 patients with extramedullary leukemia involvement or bulky adenopathy, an overall response rate (ORR) of 66.7% (four out of six patients) was achieved. Two of the nine patients with extramedullary lesions received allogeneic CAR-CD19 T cell therapy (CBM-C19.a1) and had converted mixed to complete donor chimerism at the onset of graft-versus-host disease (GVHD). One of those patients eventually died of GVHD, but the other gradually reached a complete hematologic remission and a partial regression of her extramedullary leukemic lesions. There were two Grade 2-3 toxicities and GVHD Grade 4 toxicities.

This study is registered at www.clinicaltrials.gov as NCT01864889.

CAR-T CD20 for Advanced Diffuse Large B Cell Lymphoma (DLBCL) Data Analysis

The Company also summarized the results of a Phase I clinical trial on CAR-CD20 T cell therapy (CBM-C20.1), which enrolled seven patients with chemotherapy refractory advanced diffuse large B cell lymphomas (DLBCL). One of the two patients with no bulky tumors achieved a 14-month durable and ongoing complete remission by cell infusion only, and another achieved a 6-month tumor regression achieving a complete response (CR) rate of 50% (one out of two patients) and an overall response rate (ORR) of 100% (two out of two patients). Of those patients with bulky tumor burden, four of five patients were evaluable for clinical efficacy. Of those four patients, three achieved three to six month tumor regression for an overall response rate (ORR) of 75% (three out of four patients).

Delayed toxicities related to CAR-CD20 cell infusion are directly correlated to tumor burden, and mainly included, but were not limited to, curable cytokine release symptoms and tumor lysis symptoms, and these results were achieved by combining debulking conditioning regimens in advanced DLBCL patients with bulky tumors. Overall there were three Grade 2-3 toxicities and one Grade 4 toxicity.

This study is registered at www.clinicaltrials.gov as NCT01735604. Publication source: Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells. Clin Immunol. 2014 Dec;155(2):160-75. doi: 10.1016/j.clim.2014.10.002. Epub 2014 Oct 16.

Further details of the clinical data may be viewed in the Company’s most recent presentation filed on Form 8k with the SEC, which can be found on the Company’s website at the following link, View Source under SEC filings or presentations.

The Company expects to release Phase I clinical data in the third quarter of 2015 from its clinical studies of the CAR-T constructs targeting CD30-positive Hodgkin’s lymphoma and EGFR-HER1-positive advanced lung cancer.