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Giving 65 patients with advanced pancreatic cancer a PD-L1 antibody alone or with a CTLA-4 antibody shrank tumours in 3% and 0%, so the trial was stopped before its second stage.
Part A of a two-part phase 2 randomised trial was a lead-in safety, open-label study with planned expansion pending an efficacy signal. Between November 2015 and March 2017, 65 patients with metastatic pancreatic ductal adenocarcinoma who had received one prior fluorouracil- or gemcitabine-based line were enrolled at 21 sites in 6 countries and randomised to durvalumab 1500 mg every 4 weeks plus tremelimumab 75 mg every 4 weeks for 4 cycles then durvalumab, or durvalumab monotherapy. Grade 3 or higher treatment-related adverse events occurred in 22% and 6%. Objective response rate was 3.1% for combination and 0% for monotherapy; the 10% threshold for expansion was not met and part B did not open. Patient numbers limited any association with PD-L1 expression or microsatellite instability.
Dual checkpoint blockade, which rescued other cold tumours, does not work in unselected pancreatic cancer; combinations must change the microenvironment first.
Shares Hot vs cold tumours, PD-1 / PD-L1 immune checkpoint & T-cell activation, PD-L1, Metastatic pancreatic ductal adenocarcinoma.
Shares Hot vs cold tumours, CTLA-4, PD-1 / PD-L1 immune checkpoint & T-cell activation, Metastatic pancreatic ductal adenocarcinoma.
Shares Hot vs cold tumours, CTLA-4, PD-1 / PD-L1 immune checkpoint & T-cell activation, Pancreatic ductal adenocarcinoma.
Shares Hot vs cold tumours, CTLA-4, PD-1 / PD-L1 immune checkpoint & T-cell activation, PD-L1.
Shares JAMA Oncology, Hot vs cold tumours, PD-1 / PD-L1 immune checkpoint & T-cell activation, Memorial Sloan Kettering Cancer Center.
Shares Hot vs cold tumours, Metastatic pancreatic ductal adenocarcinoma, Pancreatic ductal adenocarcinoma.
Shares Eileen M. O'Reilly, Memorial Sloan Kettering Cancer Center, Pancreatic ductal adenocarcinoma.
Shares PD-1 / PD-L1 immune checkpoint & T-cell activation, PD-L1.