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