Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Turcot Syndrome

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Antibodies

Antibodies, Monoclonal

Pembrolizumab

Immunomodulating Agents

Olaparib

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Serine

Proline

Pembrolizumab will be given as a fixed dose of 200mg standard dose on Day 1 (+/-3 days) of every 3 weeks cycle , administered intravenously as a \~30 minute infusion, as per standard clinical practice.

Olaparib dose is 300mg given orally, twice daily, from Day 1 to Day 21 continuously of each 3-week cycle. Dosing will start on day 1 of each cycle.

Pembrolizumab 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 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.

Sonia Chukwuka

Early phase team Cambridge Clincial Trials Unit -Cancer Theme

Pippa Corrie

A phase II study combining pembrolizumab with olaparib in metastatic pancreatic adenocarcinoma patients with high tumour mutation burden

This is a phase II single arm, open label, prospective trial investigating the efficacy of pembrolizumab plus olaparib in metastatic pancreatic adenocarcinoma patients exhibiting high tumour mutation burden (defined as ≥4 mutations/Mb, including tumours with Mismatch Repair Deficient (MMRD) /Microsatellite Instability (MSI) high).

Pembrolizumab With Olaparib as Combined Therapy in Metastatic Pancreatic Cancer

A Phase II Study Combining Pembrolizumab With Olaparib in Metastatic Pancreatic Adenocarcinoma (PDA) Patients With Mismatch Repair Deficiency or Tumour Mutation Burden > 4 Mutations/Mb

ORR assessed by (RECIST) version 1.1 and CT scanning every 9 weeks for the first 9 cycles (27 weeks), then 12 weekly

Safety and toxicity using NCI CTCAE version 5.0

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

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

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.

EORTC QLQC30 quality of life questionnaire. Min score 28, maximum score 112. Higher scores equal worse outcome. (Extra 2 questions: min score 1, max score 7 each. Higher scores equals better outcomes.)

EORTC PAN26 quality of life questionnaire. Min score 26, maximum score 104. Higher scores equals worse outcomes.

Spots Global Cancer Trial Database for high tumour burden