Merck Announces Partnership for Clinical Trials in Lymphoma, Melanoma Patients

Agreement with Immune Design could expand the potential of immunotherapy through combination approaches.

Immune Design and Merck have announced a partnership in combination trials of 2 Immune Design immunotherapies with Merck’s Keytruda for non-Hodgkin’s lymphoma and melanoma.

The trials will evaluate the safety and efficacy of the immuno-oncology investigative agents G100 and LV305, combined with Keytruda. 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 evaluating safety and efficacy, the trial will examine the response in both injected and non-injected lesions.

A second clinical trial will also be conducted, wherein safety and response to the combination of LV305 and Keytruda will be evaluated in patients who have not yet responded to treatment with Keytruda alone after 3 months of therapy.

Immune Design’s agents, G100 and LV305, are designed to work in vivo and activate the immune system via the induction and expansion of anti-tumor CD8 T cells. Whereas other T cell approaches require individualized ex vivo manipulation, these investigational agents are intended to be “off-the-shelf” therapies.

“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, MD, PhD, 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.”

The G100 agent is generated from the company’s GLASS discovery platform, which includes a specific formulation of Glucopyranosyl Lipid A (GLA), a synthetic, toll-like Receptor-4 (TLR-4) agonist. Preclinical and clinical data collected by Immune Design show that G100 has the ability to activate dendritic cells in tumors, while increasing antigen-dependent systemic humoral and cellular Th1 immune responses. It has an acceptable safety profile and a 50% objective response rate per protocol, according to Immune Design.

In addition to G100, LV305 will also be a part of the clinical trials. LV305 was designed to activate the immune system through the in vivo generation of cytotoxic T cells (CTLs) against specific tumor-associated antigen, NY-ESO-1. In preclinical tests, LV305 proved to reduce tumor growth of NY-ESO-1-expressing tumors; increase production of antigen-specific CD8 cells; and improve the survival of tumor-bearing animals.

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

While the therapy is indicated in the United States at a dose of 2mg/kg as an intravenous infusion, there exist some serious side effects to the drug that have affected a number of trial patients, including pneumonitis, colitis, hepatitis, nephritis, and other clinically important immune-mediated adverse reactions.

The clinical trials are still underway, but Merck and Immune Design remain hopeful in their endeavors.

“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,” said Roger M. Perlmutter, MD, PhD, president of Merck Research Laboratories.