Cabozantinib in combination with anti-PD1 immune checkpoint inhibitor in syngeneic tumor mouse models

Abstract

Conclusions: NOX-A12 alone and combined with pembrolizumab was safe and well tolerated. Changes in the cytokine signature in tumor tissue suggest that NOX-A12 modulates the tumor microenvironment and induces an immune-stimulatory Th1like signature in multiple patients of which some show signs of disease stabilization or clinical benefit. The observed time of treatment compares favorably with the expected clinical course of such end-stage and heavily pre-treated patient population.

The Multi-Kinase Inhibitor Lucitanib Enhances the Antitumor Activity of Coinhibitory and Costimulatory Immune Pathway Modulators in Syngeneic Models

“…Such efforts have led to enhanced antitumor activity and improved animal survival compared with the single agents, often accompanied by changes in the vascular and immune components of the tumor microenvironment associated with enhanced antitumor immunity. 12,[29][30][31][32][33][34][35][36][37][38][39][40][41] The concept that combining VEGF-targeted or multi-TKI therapy with immune checkpoint inhibitor therapy can improve upon the anticancer benefits of either monotherapy has been further demonstrated in multiple clinical studies, [42][43][44][45][46][47] culminating with US Food and Drug Administration (FDA) approvals for such combinations as lenvatinib+ pembrolizumab to treat advanced, nonmicrosatellite instability high/nonmismatch repair deficient endometrial cancer in patients whose disease has progressed on systemic therapy, as well as axitinib+avelumab or pembrolizumab as first-line treatments for patients with advanced renal cell carcinoma, and bevacizumab+atezolizumab for patients with unresectable or metastatic hepatocellular carcinoma who have not received prior systemic therapy. [48][49][50] Here we describe a preclinical evaluation of lucitanib in support of its development as a cancer treatment, particularly in combination with immunotherapy.…”