Preclinical studies have identified some novel and intriguing activities of Plinabulin associated with stimulation of the immune system consistent with Plinabulin's ability to enhance the activity of other immuno-oncology agents. We have observed in these preclinical studies that Plinabulin works at multiple early steps in the process of immune activation against cancer. In particular, it works to activate dendritic cells and mobilize tumor antigen-specific T-cells to the tumor. Studies in animals indicate that Plinabulin has a range of immune-enhancing effects that may be synergistic to the effects of checkpoint inhibitors, which are antibodies that inhibit a key defense mechanism that tumors employ to avoid recognition by the immune system. In preclinical studies, Plinabulin enhanced the anti-tumor efficacy of checkpoint inhibitors. We believe that Plinabulin in combination with nivolumab, a checkpoint inhibitor approved for use in NSCLC and other indications, may demonstrate more anti-tumor activity than nivolumab alone without significantly increasing toxicity. Cumulative toxicity has been a concern when nivolumab is combined with other checkpoint inhibitors.
In September 2016, UCSD enrolled the first patient in an investigator-initiated Phase 1/2 trial of Plinabulin in combination with Opdivo (nivolumab) in patients with metastatic NSCLC. In addition, the Fred Hutchinson Center, together with the University of Washington, launched an investigator-initiated Phase 1/2 trial of Plinabulin in combination with Opdivo in patients with advanced NSCLC who have failed up to two previous therapies. The Fred Hutchinson Center study had achieved the dose regimen end point and therefore the study site had been closed.
For details of these two trials, please visit below websites.