LAPC is generally defined as unresectable disease without evidence of metastatic spread, and reports suggest between 8-25% of these patients may become resectable following current standard of care (SOC) therapy. EUS-FNI allows for the delivery of drug therapies directly into the tumor, which led to the development of LSAM pac currently being evaluated in LAPC and other solid tumors by means of direct injection, where the particles of pure drug act as a depot releasing paclitaxel over several weeks.
Clinical study [NCT # 03077685] enrolled patients with LAPC, confirmed non-surgical despite SOC therapy, to additionally receive LSAM pac (NanOlogy, Inc) via EUS-FNI into the tumor during a dose-escalation phase followed by a second phase where 2 doses of 15 mg/mL LSAM pac were administered 1 month apart. The aim was to determine safety and tolerability of LSAM pac when injected directly into the lesion and assess the impact on the lesion by means of imaging assessments every 3 months following first injection. Parkview Cancer Institute (Ft Wayne, IN) enrolled 13 of the 22 subjects in the second phase of the trial.
There were no safety concerns identified. Of the 13 subjects from Parkview, seven (54%) were restaged becoming eligible for surgery following LSAM pac injections. Of the seven, 6 proceeded to surgery, 1 opted to receive alternate treatment. Five resulted in successful R0 resections, the 6th resulted in R1 resection (Table 1). Multiplex immunofluorescence analysis of biopsy samples from pre-LSAM pac and surgical specimens in 5 subjects (one pending analysis) demonstrated an increase in the density of adaptive and innate immune cells and an increase in NK cells in the tumor microenvironment, and a decrease in the myeloid/MDSC populations.
Approximately 30% of pancreatic cancer patients are considered non-surgical due to involvement of local arterial or venous structures. Existing treatment options are relatively ineffective in producing changes in the tumor to allow for conversion, and surgery still provides the best outcome. We present early findings in a series of 13 subjects with a conversion rate of 54%. LSAM pac increased the rate of conversion to resectable in these subjects without increasing toxicities associated with systemic chemotherapy. Due to theses promising results, the clinical trial is ongoing, enrolling subjects to receive up to 4 injections one month apart.
The American Journal of Gastroenterology
Sharma, Neil MD; Schmidt, C Max MD; Jain, Sushil MD; McCollom, Joseph DO; Maulhardt, Holly BS; Verco, Shelagh BSc, PhD; Rojas, Mariajose MD; Gupta, Saurabh MD; Mittal, Chetan MD; Zelt, Christina; Rumple, Ashley RN, BSN; Verco, James BS, CCRA; Perisetti, Abhilash MD; and diZerega, Gere S. MD, "Improved Resection Rates in Locally Advanced Pancreatic Cancer (LAPC) Following EUS-FNI of Large Surface Area Microparticle Paclitaxel (LSAM Pac)" (2021). PCI Publications and Projects. 60.