IND-Enabling Studies for Tumor-Penetrating Microparticles for Pancreatic Cancer
Pharmaceutical companies generally focus on drugs given by intravenous or oral administration. However, systemic therapy often does not deliver sufficient drug levels to solid tumors due to inadequate blood perfusion and high interstitial fluid pressure in tumors. On the other hand, intraperitoneal (ip) chemotherapy has demonstrated impressive survival advantage in multiple NIH-funded randomized trials conducted in 30+ years (16 months in ovarian cancer). Due to the lack of approved ip products, these earlier studies had used intravenous formulations. This approach has two limitations: (a) the restricted drug penetration to the tumor periphery diminishes the efficacy of ip treatment in patients with larger tumors (>1 cm), (b) ip therapy is associated with infection (due to indwelling catheter) and toxicity from high local drug levels (abdominal pain). These problems have prevented widespread use of ip therapy in spite of the demonstrated efficacy. Our goal is to overcome these limitations and to address the unmet need of products suitable for ip treatments.
We have developed tumor-penetrating microparticles (TPM), a first-in-class delivery system tailored to the unique anatomical properties in the peritoneal cavity. TPM comprises multicomponent, multi-functional, biocompatible, biodegradable, controlled-release polymeric micron-size particles. TPM is designed to target, penetrate and deliver pharmacodynamically optimized drug levels to the superficial and deep layers of peritoneal tumors. TPM represents a delivery platform that can be used to deliver small molecule therapeutics, biologics, gene vectors and imaging agents. The first generation TPM, TPM001, is loaded with paclitaxel.
For patients with carcinomatosis, there are no therapeutic options and only palliative treatments (e.g., costly procedures such as repeated drainage of peritoneal fluid). The first indication for TPM001 is pancreatic cancer (five-year survival is less than 5 percent).
Optimum Therapeutics, LLC
Jessie L.-S. Au, Pharm.D., Ph.D.
Ze Lu, Ph.D.
Public Health Impact
The goal of the present project is to develop an effective treatment for locoregional control of metastatic pancreatic cancer and, more generally, peritoneal tumors, which affect 230,000 new patients annually in the US.
Approved studies are ongoing.
- Stability studies
- PK/ADME studies
- IND-directed toxicology