SEATTLE, SOUTH SAN FRANCISCO, Calif. & KENILWORTH, N.J.—Immune Design, a clinical-stage immunotherapy company, has announced the establishment of clinical collaboration agreements through subsidiaries of Merck & Co., known as MSD outside of the United States and Canada. The agreements will focus on evaluating the safety and efficacy of two of Immune Design's investigative immuno-oncology agents, G100 and LV305, separately combined with Merck's KEYTRUDA in Phase 1 trials in patients with non-Hodgkin's lymphoma (NHL) and melanoma, respectively.
LV305 and G100 are meant to be “off-the-shelf” therapies, in that, unlike other T cell treatments, they don't require individualized ex-vivo manipulation. The first of the clinical trials will evaluate intratumoral administration of G100 in combination with intravenous administration of KEYTRUDA in patients with follicular NHL receiving local radiation. The key focal points of the study will be the safety of the combination as well as the tumor response in both injected and non-injected lesions. The second trial, this one in melanoma, will determine the safety and response of combining LV305 and KEYTRUDA in patients who have not yet responded to treatment with the latter after three months of administration.
"There is great potential to expand the potential of immunotherapy through combination approaches that will stimulate and enhance the immune system in order to mount the strongest response against cancer," Dr. Carlos Paya, president and CEO of Immune Design, remarked in a press release. "Immune Design has two distinct approaches in oncology, and we look forward to collaborating with Merck to evaluate the potential of combining each of G100 and LV305 with KEYTRUDA in these areas of medical need."
G100 is a product candidate generated from Immune Design's GLAAS discovery platform, which is based on Glucopyranosyl Lipid A (GLA), a small synthetic molecule that selectively binds to the toll-like receptor-4 (TLR-4) receptor to cause potent activation of dendritic cells. When GLA is combined with a tumor antigen and injected into a patient, the dendritic cells take it up, which leads to production and expansion of CD4 helper T cells and helps boost the anti-tumor immune response by expanding antigen-specific cytotoxic T cells. The compound includes a specific formulation of GLA, a synthetic, TLR-4 agonist. G100 is based on Immune Design's intratumoral immune activation approach to cancer treatment, which leverages the activation of dendritic cells, T cells and other immune cells found in the tumor microenvironment to hopefully generate a robust immune response against a tumor's diverse array of antigens.
G100 has proven capable of activating dendritic cells in tumors and increasing antigen-dependent systemic humoral and cellular Th1 immune responses in both preclinical and clinical evaluation. Enrollment was recently completed for a Phase1 study of G100 in patients with Merkel cell carcinoma, and in the first eight patients, the product candidate has demonstrated an acceptable safety profile as well as a 50-percent objective response rate per protocol.
LV305 works to activate the immune system via in-vivo generation of cytotoxic T cells initially against NY-ESO-1, a tumor-associated antigen. It was developed by Immune Design's ZVex platform, which utilizes a first-in-class vector to produce candidates that can generate cytotoxic T cells in vivo; the platform uses a re-engineered virus to carry genetic information of a tumor antigen selectively to dendritic cells in the skin, which leads to the production of cytotoxic T cells designed to kill tumor cells that present with that specific antigen. LV305 has been shown in preclinical tests to reduce tumor growth of NY-ESO-1-expressing tumors, increase production of antigen-specific CD8 and significantly improve survival for tumor-bearing animals.
At this year's ASCO annual meeting, Immune Design shared positive Phase 1 data for LV305, reporting that the product candidate engendered either a de-novo or statistically significant increase in antigen-specific CD8 T cells in 80 percent of the study's six evaluable mid- and high-dose patients. LV305 is being primarily studied as part of CMB305, a prime-boost approach.
"Our understanding of the immune system's role and its impact in the treatment of cancer continues to grow," Dr. Roger M. Perlmutter, president of Merck Research Laboratories, noted in a statement. "This collaboration with Immune Design adds to a broad clinical program designed to explore the role of KEYTRUDA in innovative immuno-oncology combinations—and underscores our commitment to advance the care of patients with cancer."