The Merck KGaA/Pfizer co-developed immune checkpoint inhibitor Avelumab will be assessed in combination with Vaccinex’s VX15/2503 through a clinical collaboration whose value was not disclosed.

Vaccinex, which announced the collaboration today, said it will conduct a Phase Ib/II clinical trial to study the combination treatment in patients with advanced non-small-cell lung cancer (NSCLC) who have not previously received immunotherapy.

“Immunotherapies have shown promise in how we treat cancer, and the investigation of combination therapies may uncover additional possibilities,” Vaccinex President and CEO Maurice Zauderer, Ph.D., said in a statement.

Avelumab—the lead immuno-oncology compound in Merck KGaA's pipeline also known as MSB0010718C—is a fully human anti-programmed death ligand 1 (anti-PD-L1) immunoglobulin G1 (IgG1) monoclonal antibody. By inhibiting PD-L1 interactions, avelumab is thought to potentially enable the activation of T cells and the adaptive immune system. Avelumab may also help white blood cells such as natural killer (NK) cells find and attack tumors through a process called antibody-dependent cell-mediated cytotoxicity (ADCC).

Merck KGaA and Pfizer are co-developing avelumab through an alliance launched in 2014 that could generate up to $2.85 billion for the German drug developer.

VX15/2503 is a novel monoclonal antibody designed to block the activity of semaphorin 4D (SEMA4D, CD100). Dr. Zauderer noted that a Phase I study of VX15/2503 monotherapy had shown potential for use in combination treatments.

The two-center, Phase I, multiple ascending-dose clinical trial studied the VX15/2503 anti-SEMA4D antibody in 42 adults with advanced solid tumors. According to Vaccinex, 17 of the 42 participants at all dose levels exhibited stable disease for at least 8 weeks and 9 patients showed stable disease for 16 or more weeks. Patients with the longest duration of treatment (48–55 weeks) included colorectal, breast, and a papillary thyroid patient who had a partial response by Response Evaluation Criteria for Solid Tumors (RECIST), and stable disease for at least 6 months following cessation of treatment at 48 weeks.

In preclinical studies, Vaccinex said, anti-SEMA4D antibodies had been shown to increase infiltration of tumoricidal immune cells while simultaneously reducing multiple types of immunosuppressive cells in tumors. Anti-SEMA4D antibodies were also found to synergize with a checkpoint inhibitor antibody to promote tumor eradication.

VX15/2503 is also under development for Huntington’s disease—for which the candidate won the FDA’s Orphan Drug designation in August—and multiple sclerosis, as SEMA4D plays a role in multiple cellular processes that contribute to pathophysiology of neuroinflammatory/neurodegenerative diseases.

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