Phase I study evaluating the safety and preliminary anti-tumor efficacy of receptor mediated bispecific nano-immunoengager in advanced solid tumors

Background

Immune checkpoint inhibitors (ICI) are integral in the treatment of solid malignancies. However, treatment responses vary and don’t always lead to remissions. Disruption in T_eff cell homing is one proposed resistance mechanism. Receptor mediated bispecific nano-immunoengager (NIE) is being developed at UC Davis and a potential strategy to overcome immunotherapy resistance. NIE binds to tumor cells and transforms into a nanofibrillar network at the tumor microenvironment; it then recruits Teff cells and modifies the immunosuppressive TME.

Methods

This is a phase I dose escalation study with an expansion cohort at a single site to evaluate safety and preliminary anti-tumor efficacy of NIE alone and in combination with pembrolizumab. We will enroll patients with recurrent metastatic solid tumors with progression on prior ICI. 14 patients will be enrolled for dose escalation with NIE monotherapy. The Bayesian optimal interval (BOIN) design will be employed to establish the recommended expansion dose. The expansion cohorts will include 10 patients with NSCLC-adenocarcinoma and 10 patients with other solid tumors. Patients will receive NIE at the recommended expansion dose in combination with pembrolizumab.

Results

Preliminary safety and anti-tumor efficacy of receptor mediated bispecific nano-immunoengager is supported by pre-clinical studies in 4T1 breast cancer and Lewis lung cancer murine models. Mice treated with NIE had a higher proportion of CD8 T cells, decreased Ki-67 expression, greater IHC expression of M1 vs M2 macrophage markers, and increased expression of pro-inflammatory chemokines. Combination treatment with NIE and anti PD-1 antibody led to complete elimination of tumor without signs of recurrence at 90 days or signs of weight loss or dehydration.

Conclusion

Pre-clinical data supports the synergistic anti-tumor activity and safety of NIE with ICI. NIE is a potential strategy to overcome resistance to ICI, which is a key pillar in cancer. This phase I study will NIE alone in human participants.