A phase II study combining pembrolizumab with olaparib in metastatic pancreatic adenocarcinoma patients with high tumour mutation burden
Aged ≥ 18 years old
Written informed consent
Histologically or cytologically confirmed PDA
Confirmation that the PDA has TMB >4 mutations/Mb, or dMMR gene mutation, or MSI-H by IHC. TMB status and dMMR can be obtained from either tissue, or blood.
Patients with resectable or locally advanced PDA
Other invasive malignancies diagnosed within the last 2 years which have not been treated with curative intent
Prior immune checkpoint inhibitors or PARP inhibitors. This includes any prior therapy with an anti-PD-1, or anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g, CTLA-4, OX 40, CD137)
Requirement for non-physiological dose of daily oral steroids, or regular use of any other immunosuppressive agents; prednisolone dose of < 10mg (or equivalent steroid dose) is allowed. Use of inhaled or topical steroids is allowed.
Single group
Pembrolizumab
DrugPembrolizumab is a highly selective immunoglobulin G4-kappa humanised monoclonal antibody against Programmed cell death protein 1 (PD-1) receptor. It was generated by grafting the variable sequences of a very high-affinity mouse antihuman PD-1 antibody onto a human IgG4-kappa isotype with the containing a stabilizing Serine 228 to Proline Fc mutation.
Olaparib
DrugOlaparib is a potent inhibitor of polyadenosine 5'diphosphoribose polymerase (PARP) developed as a monotherapy as well as for combination with chemotherapy, ionising radiation and other anti-cancer agents including novel agents and immunotherapy.
Objective Response Rate (ORR)
ORR assessed by (RECIST) version 1.1 and CT scanning every 9 weeks for the first 9 cycles (27 weeks), then 12 weekly
Incidence of adverse events (Safety and toxicity)
Safety and toxicity using NCI CTCAE version 5.0
Duration of Response (DOR)
DOR: the time (in days) from the first documentation of objective response (complete response or partial response, confirmed or unconfirmed, whichever status was recorded first, using RECIST criteria) until the first documented disease progression, or death (if before progression
Progression Free Survival (PSF)
PFS: the time from registration to disease progression, or death, whichever occurs first, assessed by the treating investigators. Patients who remained alive without disease progression at the time of data analyses are censored at their last date of clinical follow-up for progression. Median, 1 year and 2 year PFS rates will be measured
Overall survival (OS)
OS: the time from registration to death. Patients who remain alive are censored at their last contact date for OS. Median, 1 year and 2 year OS rates will be measured.
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Cambridge University Hospitals NHS Foundation Trust
Lead sponsor
National Institute for Health Research, United Kingdom
Collaborator
