Vaccibody AS and Nektar Therapeutics announced the first patient has been dosed in the combination therapy of the Phase 1/2a study evaluating bempegaldesleukin (bempeg), Nektar's CD122-preferential IL-2 pathway agonist, with VB10.NEO, Vaccibody's personalized neoantigen cancer vaccine, in patients with advanced squamous cell carcinoma of the head and neck (SCCHN).

"We're pleased to advance our collaboration with Vaccibody to evaluate the potential of bempeg given with a personalized vaccine, VB10.NEO, in patients with advanced head and neck cancer," said Jonathan Zalevsky, Ph.D., Chief Research & Development Officer at Nektar. "The rationale for this clinical study is supported by our promising preclinical data which demonstrated how a personalized cancer vaccine and a T cell proliferator can work synergistically to induce maximal expansion of vaccine-induced T cell clones, provide deep and durable responses and, at the same time, offer specific anti-tumor immunity."

VB10.NEO is designed to specifically activate a patient's immune system to tumor-specific antigens, called neoantigens, while bempeg is designed to expand and proliferate tumor antigen-specific T cells in the periphery and in the tumor microenvironment. Addition of bempeg to VB10.NEO is intended to drive maximal expansion of vaccine-induced neoantigen-specific T cells for the treatment of cancer.

At the 2019 Society for Immunotherapy of Cancer (SITC) Annual Meeting, Vaccibody presented interim data for VB10.NEO in a group of patients with various solid tumor types who had all received multiple lines of prior anti-cancer therapy and had been treated with at least one checkpoint inhibitor (CPI) (nivolumab or pembrolizumab) for a range of 5 to 32 months. The data presented showed that 50 percent (7/14) of patients treated with VB10.NEO achieved clinical responses, including four patients with SCCHN. Clinical response was defined as either >10% reduction in the target lesions (as identified at screening) or converting progressive lesions into stable lesions (<20% increase, up to 37 weeks follow-up).

"We are pleased that our initial data with VB10.NEO demonstrated that the vaccine induced strong neoantigen-specific T cell responses and clinical benefit, particularly in patients who did not respond to checkpoint inhibitor monotherapy," said Agnete Fredriksen, President and Chief Scientific Officer of Vaccibody and continued: "We believe combining bempeg, a T cell stimulator, with VB10.NEO can further drive the expansion of VB10.NEO elicited neoantigen-specific T cells and potentially deepen and broaden anti-tumor activity. Siri Torhaug, Chief Medical Officer of Vaccibody added, "We are happy to announce the first patient dosed with the combined therapy of VB10.NEO and bempegaldesleukin and look forward to seeing the first read outs from this unique approach in patients with head and neck cancer."

Preclinical studies evaluating the combination of VB10.NEO and bempeg demonstrated the synergy of the two mechanisms to elicit greater breadth and depth of neoantigen-specific T cell responses as compared to each agent individually.  In preclinical models of solid tumors, the combination induced strong immunogenic CD8+ T cell responses, and when combined with anti-PD-1, induced rapid, complete and durable tumor regression of small tumors, and long-lasting disease control of large tumors.

VB10.NEO, is Vaccibody's proprietary therapeutic DNA vaccine which uses the patient's own neoantigens for the personalized treatment of cancer patients. A phase 1/2a neoantigen clinical trial is currently enrolling patients with locally advanced or metastatic melanoma, non-small cell lung carcinoma, clear renal cell carcinoma as well as urothelial cancer or squamous cell carcinoma of the head and neck. In clinical trials, VB10.NEO has demonstrated induction of strong neoantigen-specific immune responses which led to clinical responses in patients with locally advanced or metastatic disease.

Bempegaldesleukin is designed to stimulate cancer-killing immune cells in the body by targeting CD122 receptors found on the surface of these immune cells. CD122, which is also known as the Interleukin-2 receptor beta subunit, is a key signaling receptor that is known to increase proliferation of these effector T cells. In clinical and preclinical studies, treatment with bempegaldesleukin resulted in expansion of these cells and mobilization into the tumor micro-environment.