Ibrutinib Combined With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Pancreatic Cancer

Summary

Gemcitabine and nab-paclitaxel is a standard regimen (NCCN, Category 1) for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). However, further improvement in treatment is needed. Increasingly, the nature of the immune infiltrate in PDAC appears to be tumor promoting. In preclinical studies, ibrutinib treatment, presumably by reprogramming B cells, results in increased CD8+ T cells to assist in tumor control. Preclinical studies of ibrutinib plus gemcitabine show superior antitumor effects compared to gemcitabine alone in both orthotopic murine pancreatic cancer cell line grafts and in genetically engineered mouse models. Thus, the investigators propose a clinical trial of ibrutinib plus the standard gemcitabine based regimen of gemcitabine and nab-paclitaxel, evaluating safety, then efficacy and including correlative studies.

Timeline

Start

2015-10-12

Primary completion

2019-11-15

Completion

2020-09-01

Publications

• Sinha M, Betts C, Zhang L, Griffith MJ, Solman I, Chen B, Liu E, Tamaki W, Stultz J, Marquez J, Sivagnanam S, Cheung A, Pener D, Fahlman A, Taber E, Lerner K, Crocker M, Todd K, Rajagopalan B, Ware C, Bridge M, Vo J, Dragomanovich H, Sudduth-Klinger J, Vaccaro G, Lopez CD, Tempero M, Coussens LM, Fong L. Modulation of myeloid and T cells in vivo by Bruton's tyrosine kinase inhibitor ibrutinib in patients with metastatic pancreatic ductal adenocarcinoma. J Immunother Cancer. 2023 Jan;11(1):e005425. doi: 10.1136/jitc-2022-005425.

Drugs

Indications