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
1 other identifier
interventional
20
1 country
13
Brief Summary
A phase II study combining pembrolizumab with olaparib in metastatic pancreatic adenocarcinoma patients with high tumour mutation burden
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2 pancreatic-cancer
Started Feb 2025
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 3, 2021
CompletedFirst Posted
Study publicly available on registry
October 26, 2021
CompletedStudy Start
First participant enrolled
February 26, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 1, 2028
September 18, 2025
September 1, 2025
2.4 years
June 3, 2021
September 16, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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
Through study completion, an average of 2 years
Secondary Outcomes (6)
Incidence of adverse events (Safety and toxicity)
Through study completion, an average of 2 years
Duration of Response (DOR)
Through study completion, an average of 2 years
Progression Free Survival (PSF)
through study completion, a maximum of 2 years
Overall survival (OS)
through study completion, a maximum of 2 year
European Organisation for Research and Treatment of Cancer Quality of Life of Cancer Patients questionnaire (EORTC QLQC30)
Every 9 weeks during the first 27 weeks and then every 12 weeks until death or maximum of 2 years
- +1 more secondary outcomes
Study Arms (1)
Pembrolizumab and olaparib
EXPERIMENTALPembrolizumab 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.
Interventions
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.
Eligibility Criteria
You may qualify if:
- 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.
- Radiologically confirmed stage 4 mPDA, with measurable disease
- Received no more than 1 prior systemic therapy regimen for unresectable (stage 3 or 4) PDA is allowed
- Measurable disease which has not been irradiated in prior radiotherapy
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
- Life expectancy \>12 weeks from the date of screening assessment
- Adequate bone marrow function:
- Absolute neutrophil count (ANC) ≥1.5 x 109 /L
- Haemoglobin (Hb) ≥ 90 g/L
- Platelets ≥100 x 109 /L
- Adequate liver function:
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤2.5 x upper limit of normal range (ULN), or \<5 x ULN in the presence of liver metastases
- +2 more criteria
You may not qualify if:
- 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.
- Significant acute or chronic medical or psychiatric condition, disease or laboratory abnormality, which in the judgment of the investigator would place the patient at undue risk or interfere with the trial. Examples include, but are not limited to:
- A history of chronic obstructive pulmonary disease, interstitial lung disease, sarcoidosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis, cystic fibrosis or bronchiectasis affecting pulmonary function, causing breathlessness at rest
- Uncontrolled ischaemic heart or other cardiovascular event (myocardial infarction, new angina, stroke transient ischaemic attack, or new congestive cardiac failure) within the last 2 months
- Stable but significant cardiovascular disease defined by heart failure (New York Heart Association Functional Classification III or IV) or frequent angina
- Presence of active infection
- Cirrhotic liver disease, known HIV, chronic active or acute hepatitis B, or hepatitis C
- History of severe allergy or hypersensitivity reactions
- Autoimmune disease requiring chronic use of immunosuppressive agents.
- Replacement therapy using physiological doses for adrenal or pituitary insufficiency is allowed.
- Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
- Has known brain metastases and/or carcinomatous meningitis
- +14 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (13)
Addenbrooke's Hospital
Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom
Velindre Cancer Centre
Cardiff, CF14 2TL, United Kingdom
University Hospitals Coventry and Warwickshire
Coventry, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom
St James' University Hospital
Leeds, United Kingdom
Guy's and St Thomas' NHS Foundation Trust
London, United Kingdom
Royal Free Hospital
London, United Kingdom
University College London Hospitals NHS Foundation Trust
London, United Kingdom
The Christie
Manchester, United Kingdom
Milton Keynes University Hospital
Milton Keynes, United Kingdom
Norfolk and Norwich University Hospital
Norwich, United Kingdom
Nottingham University Hospitals NHS Foundation Trust
Nottingham, United Kingdom
Derriford Hospital
Plymouth, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Pippa Corrie
Cambridge University Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Chief Investigator
Study Record Dates
First Submitted
June 3, 2021
First Posted
October 26, 2021
Study Start
February 26, 2025
Primary Completion (Estimated)
July 31, 2027
Study Completion (Estimated)
January 1, 2028
Last Updated
September 18, 2025
Record last verified: 2025-09
Data Sharing
- IPD Sharing
- Will not share