{"entity":{"id":"paper-oreilly-durvalumab-tremelimumab-pancreatic-jama-oncol-2019","kind":"paper","name":"Durvalumab with or without tremelimumab for patients with metastatic pancreatic ductal adenocarcinoma: a phase 2 randomized clinical trial","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-24","links":[{"label":"O'Reilly et al., JAMA Oncol 2019: durvalumab with or without tremelimumab in 65 metastatic patients","url":"https://doi.org/10.1001/jamaoncol.2019.1588"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31318392/"}],"tags":[],"related":[],"cancers":["pancreatic","metastatic-pdac"],"sections":[],"technologies":[],"targets":["pdl1","ctla4"],"drugs":["durvalumab"],"companies":[],"institutions":["mskcc"],"pathways":["pd1-checkpoint"],"terms":["cold-vs-hot"],"trials":[],"people":["eileen-oreilly"],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2019,"doi":"10.1001/jamaoncol.2019.1588","pmid":"31318392","authors":"O'Reilly EM, Oh DY, Dhani N, et al.","paperType":"rct","findings":["Objective response 3.1% with durvalumab plus tremelimumab and 0% with durvalumab alone.","Trial did not expand: the 10% efficacy threshold was not met."],"whatItMeans":"Dual checkpoint blockade, which rescued other cold tumours, does not work in unselected pancreatic cancer; combinations must change the microenvironment first.","caveats":["Second-line population with rapidly progressing disease.","No biomarker selection and small numbers."],"changedPractice":false,"participants":65},"route":"/key-papers/paper-oreilly-durvalumab-tremelimumab-pancreatic-jama-oncol-2019/","neighbours":{"cancer":[{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal adenocarcinoma","route":"/cancers/metastatic-pdac/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"target":[{"id":"ctla4","kind":"target","name":"CTLA-4","route":"/targets/ctla4/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"}],"drug":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}],"institution":[{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"}],"pathway":[{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"}],"term":[{"id":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","route":"/terms/cold-vs-hot/"}],"person":[{"id":"eileen-oreilly","kind":"person","name":"Eileen M. O'Reilly","route":"/people/eileen-oreilly/"}],"journal":[{"id":"jama-oncology","kind":"journal","name":"JAMA Oncology","route":"/journals/jama-oncology/"}]}}