LASP-04: Tolerance Evaluation of Experimental Compound in Kras/p53 Pancreatic Ductal Adenocarcinoma (PDAC) Mice

The Laboratory Animal Sciences Program will breed 18 KPC animals with the intent of generating a cohort of 12 animals with confirmed tumor-load matching the following enrollment criteria: female mice are considered eligible for enrollment when ultrasound examination within 24 hours reveals 1 or 2 tumors, with the largest size being 6–11 mm and a combined tumor volume of 100–350 mm3. Animals with three or more tumors per organ; cystic tumors; signs of intestinal, pancreatic, or gall bladder duct occlusions; or otherwise moribund/showing signs of dilapidation will not be included in the study. Tumor-bearing mice will be assembled and randomized into three treatment arms (four animals per arm: vehicle, experimental compound at dose level A, and experimental compound at dose level B). Dosing will be oral at QDx21. Animals will be processed for terminal blood collection and full necropsy (at a pre-specified timepoint upon administering the last dose), following the toxicologic pathology guidelines. Cryopreserved plasma samples and tissues from PDAC tumor, lung, liver, and skeletal muscle will be provided for histology/pathology evaluation.

This service will take about three months to complete, and the Laboratory Animal Sciences Program will provide collected cryopreserved tissues and blood plasma. Sufficient basic consultation with a subject matter expert is included with the service.

Group

Treatment

Dose

Collection at

1

Vehicle

PO, QD x 21

X hours post-last dose

4

2

AE1 (Dose A)

PO, QD x 21

X hours post-last dose

4

3

AE1 (Dose B)

PO, QD x 21

X hours post-last dose

4