Chrystal U Louis
Merrimack Pharmaceuticals, Cambridge, USA
Title: A Multi-targeted Approach to Treating Pancreatic Cancer
Biography
Biography: Chrystal U Louis
Abstract
Pancreatic cancer often presents as inoperable, locally-advanced or metastatic disease. With traditional forms of chemotherapy, long-term survival for patients with metastatic disease is less than 5%. Due to the heterogeneity within pancreatic lesions, investigators are beginning to tailor treatment regimens to the pathology and biology of individual tumors. Using a systems engineering approach, we have developed both targeted and untargeted nanoliposomal molecules as well as signaling inhibitors to combat malignant solid tumors like pancreatic cancer. Nal-IRI (liposomal irinotecan, ONIVYDE®), MM-310 (EphA2-targeted docetaxel nanoliposome), and istiratumab (a tetravalent IGF-1R and ErbB3 inhibitor) are three examples of novel therapeutic candidates designed to utilize the tumor biology and microenvironment to improve anti-tumor efficacy. Nal-IRI takes advantage of both leaky vasculature and tumor associated macrophages within the tumor environment to enhance delivery and activity of SN-38. With an EphA2-targeting arm, MM-310 is a next generation nanoliposome providing enhanced delivery and specificity of docetaxel to EphA2-positive malignancies. Lastly, istiratumab inhibits pro-survival signaling through the PI3K/AKT/mTOR pathway by blocking and subsequently stripping IGF-1R and ErbB3 from the surface of tumor cells. Nal-IRI is currently being investigated in combination with 5FU, leucovorin, and oxaliplatin in patients with newly diagnosed metastatic pancreatic cancer. Targeted (biomarker-driven) patient selection is being utilized in both the Phase 1 study of MM-310 for patients with EphA2-positive cancers, and in the Phase 2 study of istiratumab in combination with nab-paclitaxel and gemcitabine in newly diagnosed metastatic pancreatic cancer patients who have elevated levels of free IGF-1 in their serum.