Effect of anti-CTGF human recombinant monoclonal antibody pamrevlumab on resectability and resection rate when combined with gemcitabine/nab-paclitaxel in phase 1/2 clinical study for the treatment of locally advanced pancreatic cancer patients.

Abstract

4016Background: Pancreatic ductal adenocarcinomas exhibit high degree of desmoplasia with extensive connective tissue growth factor (CTGF) expression and extracellular matrix production. CTGF overexpression is associated with aberrant fibrous tissue in mouse model, in which progression of tissue adhesion was inhibited by pamrevlumab. We hypothesize that pamrevlumab, an anti-CTGF antibody, may influence resectability of locally advanced pancreatic cancer (LAPC) by inhibiting effects of CTGF. Methods: Pamrevlumab + gemcitabine/Nab-paclitaxel (G/N) (Arm A) vs G/N (Arm B) was given to treatment-naive LAPC patients to improve resection rate and overall survival (OS). Patients (N = 37) were randomized 2:1 in Arm A vs Arm B. Patients who completed 6 cycles of treatment underwent resectability assessment per protocol criteria (NCCN, CA 19-9, PET, RECIST) and, if found eligible, underwent resection. No adjuvant therapy was given; second line therapy was administered per investigator discretion. Results: In the ITT...