Immune Design, a clinical-stage immunotherapy company, has entered into clinical collaboration agreements through subsidiaries of Merck, a global healthcare leader, to evaluate the safety and efficacy of two Immune Design immuno-oncology investigative agents, G100 and LV305, separately combined with Keytruda (pembrolizumab), Merck’s anti-PD-1therapy, in phase 1 trials in patients with non-Hodgkin’s lymphoma (NHL) and melanoma, respectively.

The first clinical trial will examine intratumoral administration of G100 with intravenous administration of Keytruda in patients with follicular NHL receiving local radiation. In addition to an evaluation of the safety of the combination, the study will assess the response in both injected and non-injected lesions. The second clinical trial in melanoma will evaluate safety and response to the combination of LV305 and Keytruda in patients who have not yet responded to treatment with Keytruda alone after three months of treatment.

Immune Design’s G100 and LV305 investigational agents are designed to work in vivo and activate the immune system via the induction and/or expansion of anti-tumour CD8 T cells. They are intended to be “off-the-shelf” therapies, in contrast to other T-cell approaches that require individualised ex vivo manipulation. G100 is a potent toll-like receptor-4 (TLR4) agonist designed to generate a robust anti-tumour immune response when administered directly to the tumour micro-environment. LV305, in contrast, is designed to activate the immune system through the in vivo generation of cytotoxic T cells (CTLs), initially against a specific tumour-associated antigen, NY-ESO-1. Immune Design is studying LV305 primarily as part of CMB305, a prime boost approach currently in a phase 1 expansion trial.

“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,” said Carlos Paya, M.D., Ph.D, president and chief executive officer of Immune Design.

“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.”

“Our understanding of the immune system’s role and its impact in the treatment of cancer continues to grow,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. “This collaboration with Immune Design adds to a broad clinical programme designed to explore the role of Keytruda in innovative immuno-oncology combinations – and underscores our commitment to advance the care of patients with cancer.”

G100 is a product candidate generated from the company's GLAAS discovery platform, and includes a specific formulation of glucopyranosyl lipid A (GLA), a synthetic, toll-like receptor-4 (TLR-4) agonist. G100 is part of Immune Design's intratumoral immune activation, or ‘endogenous antigen’ approach to treating cancer, which leverages the activation of dendritic cells, T cells and other immune cells in the tumour microenvironment to potentially create a robust immune response against the tumour's preexisting diverse set of antigens. Preclinical and clinical data have demonstrated the ability of G100 to activate dendritic cells in tumours and to increase antigen-dependent systemic humoral and cellular Th1 immune responses. In addition to the study planned under this collaboration, a phase 1 study of G100 in patients with Merkel cell carcinoma (MCC) recently completed enrollment, and Immune Design presented data at the 2015 American Society of Clinical Oncology (ASCO) annual meeting. In the first eight patients in MCC study, G100 has an acceptable safety profile and a fifty per cent objective response rate per protocol.

LV305, generated from Immune Design’s ZVex platform, is designed to activate the immune system through the in vivo generation of cytotoxic T cells (CTLs) initially against a specific tumour-associated antigen, NY-ESO-1. LV305 is part of Immune Design’s ‘Specific Antigen’ approach, which drives the in vivo generation of a strong, antigen-specific CTL response against selected antigens present in a tumour. Preclinical tests have demonstrated the ability of LV305 to reduce tumor growth of NY-ESO-1-expressing tumours, increase production of antigen-specific CD8 cells, and significantly improve the survival of tumor-bearing animals. LV305 is the first step in Immune Design’s novel prime-boost approach to immuno-oncology, which includes combination with G305, generated from the GLAAS platform, to expand CTLs and potentially generate a potent, durable immune response. Immune Design announced positive data from a phase 1 study of LV305 at the 2015 ASCO annual meeting. In that study, LV305 caused either a de novo or statistically-significant increase in antigen-specific CD8 T cells in 80 per cent of the six evaluable mid- and high-dose patients. Immune Design is primarily studying LV305 as part of CMB305, a prime boost approach.

Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. By binding to the PD-1 receptor and blocking the interaction with the receptor ligands, Keytruda releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.

Keytruda is indicated in the United States at a dose of 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merck is advancing a broad and fast-growing clinical development program for Keytruda with more than 100 clinical trials – across more than 30 tumour types and over 16,000 patients – both as a monotherapy and in combination with other therapies.