The CCTG PA.7 phase II trial of gemcitabine and nab-paclitaxel with or without durvalumab and tremelimumab as initial therapy in metastatic pancreatic ductal adenocarcinoma
Daniel J. Renouf, Jonathan M. Loree, Jennifer J. Knox, James T. Topham, Petr Kavan, Derek J. Jonker, Stephen Welch, Félix Couture, Frédéric Lemay, Mustapha Tehfé, Mohammed Harb, Nathalie Aucoin, Yoo‐Joung Ko, Patricia A. Tang, Ravi Ramjeesingh, Brandon M. Meyers, Christina Kim, Pan Du, Shidong Jia, David F. Schaeffer, Sharlene Gill, Dongsheng Tu, Chris J. O’Callaghan
Abstract
Immunotherapy-based monotherapy treatment in metastatic pancreatic ductal adenocarcinoma (mPDAC) has shown limited benefit outside of the mismatch repair deficiency setting, while safety and efficacy of combining dual-checkpoint inhibitor immunotherapy with chemotherapy remains uncertain. Here, we present results from the CCTG PA.7 study (NCT02879318), a randomized phase II trial comparing gemcitabine and nab-paclitaxel with and without immune checkpoint inhibitors durvalumab and tremelimumab in 180 patients with mPDAC. The primary endpoint was overall survival. Secondary endpoints included progression-free survival and objective response rate. Results of the trial were negative as combination immunotherapy did not improve survival among the unselected patient population (p = 0.72) and toxicity was limited to elevation of lymphocytes in the combination immunotherapy group (p = 0.02). Exploratory baseline circulating tumor DNA (ctDNA) sequencing revealed increased survival for patients with KRAS wildtype tumors in both the combination immunotherapy (p = 0.001) and chemotherapy (p = 0.004) groups. These data support the utility of ctDNA analysis in PDAC and the prognostic value of ctDNA-based KRAS mutation status.