On March 26, 2015 Immune Design reported the dosing of patients in a Phase 1b clinical trial of CMB305, a "prime-boost" immuno-oncology product candidate generated from the company’s ZVexTM and GLAASTM platforms (Press release, Immune Design, MAR 26, 2015, View Source [SID:1234502560]). CMB305 is the first product candidate of Immune Design’s Specific Antigen approach, which is one of the company’s two distinct approaches to fighting cancer.

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CMB305 is a novel combination product that involves the sequential dosing of two complementary agents, LV305 and G305, and is designed to synergistically induce anti-tumor cytotoxic T lymphocytes (CTLs) to target tumors that express NY-ESO-1, a tumor antigen found in a broad set of tumors.

"CMB305’s prime-boost approach leverages the activation of two separate arms of the patient’s immune system, that when combined under this novel approach, are designed to induce a strong and long lasting anti-tumor CD8 T cell response, as well as activate other complementary immune effectors that may help to fight cancer," said Carlos V. Paya, MD, PhD, chief executive officer of Immune Design.

The Phase 1b open label, multi-center trial (NCT02387125) is designed to evaluate the safety and tolerability, immunogenicity, and preliminary clinical efficacy of CMB305 in patients with locally advanced, relapsed or metastatic solid cancers expressing NY-ESO-1. The study is divided into two parts. Part 1 is a dose escalation study in up to 12 patients. Part 2 will be an expansion study of the optimal dose in approximately 27 patients.

About CMB305

CMB305 is an immuno-oncology product candidate combining two potentially synergistic agents. The first agent, LV305, is a hybrid vector from the ZVex platform that specifically targets dendritic cells (DCs) in vivo and delivers the RNA for NY-ESO-1, enabling the DCs to express the entire tumor antigen to potentially induce a diverse set of CTLs. G305 is the second agent and is designed to boost the CTL response via the induction of antigen-specific CD4 "helper" T cells. G305 consists of recombinant NY-ESO-1 protein formulated with a proprietary synthetic small molecule called glucopyranosyl lipid A (GLA), the novel TLR4 agonist at the core of the GLAAS platform. CMB305 is intended to be an "off-the shelf" therapy that does not require patient-specific manufacturing or ex vivo manipulation of patient samples. The NY-ESO-1 protein is provided by the Ludwig Institute for Cancer Research.

On March 26, 2015 Oncolytics Biotech reported that Dr. Giovanni Selvaggi MD, Vice President, Clinical Development, made a presentation titled "REOLYSIN and Immune Checkpoint Inhibitors: Rationale for Combination Therapy" at the 2015 Immune Checkpoint Inhibitors meeting being held from March 24th to 26th in Boston, MA (Press release, Oncolytics Biotech, MAR 26, 2015, View Source [SID:1234502558]). The presentation included data from single arm clinical studies in patients with primary glioblastomas or brain metastases (REO 013b) and advanced pancreatic cancer (REO 017), as well as preclinical data.

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Highlights of the data presented include:

REOLYSIN inducing the up-regulation of PD-1 and PD-L1 in target tissues in patients with primary glioblastomas or brain metastases, and that this up-regulation is strongly associated with productive reoviral infection (REO 013b);
The combination of REOLYSIN and gemcitabine inducing PD-L1 expression in tumour samples from pancreatic cancer patients (REO 017); and
The combination of REOLYSIN, GM-CSF, anti-PD-1 and anti-CTLA-4 improved survival in immune competent mice versus REOLYSIN and GM-CSF alone and REOLYSIN and GM-CSF plus either one of the checkpoint inhibitors alone.

"The anti-PD-1/PD-L1 class of drugs is currently one of the most promising new therapeutic areas in oncology and works by helping the body’s immune system recognize and eliminate tumours," said Dr. Brad Thompson, President and CEO of Oncolytics. "Higher levels of PD-1 and PD-L1 may improve this class of drugs’ effectiveness. The discovery that PD-1 and PD-L1 are up-regulated or increased in tumours in patients treated with REOLYSIN, combined with our animal model data findings to this point, may indicate that REOLYSIN is a potentiator for the entire anti-PD-1/PD-L1 drug class. We intend to immediately incorporate these findings into our clinical program."

REO 013b (brain) is a U.K. open-label, non-randomized, single-center study of REOLYSIN given intravenously to patients prior to planned surgery for recurrent high grade primary or metastatic brain tumours in advance of their scheduled operations to remove brain tumours.

REO 017 is a U.S. Phase II single-arm clinical trial using intravenous administration of REOLYSIN in combination with gemcitabine (Gemzar) in chemotherapy-naïve patients with advanced or metastatic pancreatic cancer.

A copy of the presentation will be available on the Oncolytics website at: View Source

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.