A multicenter randomized phase II study of NPC-1C (N) in combination with gemcitabine (G) and nab-paclitaxel (A) versus G and A alone in patients with metastatic or locally advanced pancreatic cancer (PC) previously treated with folfirinox (F).
Duffy, AG; Beg, MS; Greten, TF; Beatson, MA; Mavroukakis, S; Patel, SP; Morse, MA; Arlen, PM
Published in: Journal of Clinical Oncology
TPS499 Background: PC carries a poor prognosis. F has improved overall survival (OS) compared to G leading to its use as a 1st line treatment for patients (pts) with advanced PC. Similarly, the combination of G and A has demonstrated OS benefit. No data exists for G/A in the 2nd line setting. Many oncologists continue to sequence F treatment followed upon disease progression by G/A for pts with advanced PC with good performance status. N is a chimeric monoclonal IgG1 antibody recognizing an aberrantly glycosylated MUC5AC specific to GI tumors. Its mechanism of action is through ADCC. An IHC based companion diagnostic assay is utilized to select pts whose tumors express the target (approx. 65-70%). A prior study administering N to pts with advanced PC refractory to chemotherapy was well tolerated with disease stabilization and prolongation of OS. Furthermore 2 of 5 pts receiving the combination of G+N following progression on F remain alive at 10 and 12 months respectively. Methods: The primary objective of this phase 2.5 study is to determine if the combination of N and G plus A can improve the OS for pts who have PC over G plus A alone in the post F setting. The trial is a 2-arm randomized 1:1 multi-institution trial of N plus G and A vs. G and A. Eligible pts would be expected to have an estimated 4.5 to 4.8 month median OS with G alone, but this may be enhanced somewhat with the addition of A. The goal is to determine if the use of N along with G and A will result in pts having an increased median OS of 8 months vs. an estimated 5 months without N. Kaplan-Meier curves and a two-tailed log-rank test will be the primary analysis methods. All pts must have tissue positive for the MUC5AC variant (≥20% by IHC). Because N has been established to be safe when given with G alone but not with the combination of G and A, stopping rules for safety will be adhered to for the first 6 pts randomized to G/A plus N. Enrollment to the study has commenced. Correlative studies will utilize both PBMCs and serum for immune monitoring. Frequency, phenotype and function of different immune cells (including CD8+ T cells, CD4+ T cells, Tregs and MDSCs) will be analyzed. Clinical trial information: NCT01834235.
