Pembrolizumab With Olaparib as Combined Therapy in Metastatic Pancreatic Cancer

September 16, 2025 updated by: Pippa G Corrie, PhD FRCP, Cambridge University Hospitals NHS Foundation Trust

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

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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).

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Early phase team Cambridge Clincial Trials Unit -Cancer Theme
  • Phone Number: 01223348454
  • Email: cuh.cctuep@nhs.net

Study Contact Backup

  • Name: Clinical Trial Coordinator
  • Phone Number: +44 01223348454
  • Email: cuh.pemola@nhs.net

Study Locations

  • United Kingdom
      • Cardiff, United Kingdom, CF14 2TL
        • Recruiting
        • Velindre Cancer Centre
        • Contact:
        • Principal Investigator:
          • Seema Arif
      • Coventry, United Kingdom
        • Recruiting
        • University Hospitals Coventry and Warwickshire
        • Principal Investigator:
          • Martin Scott-Brown
        • Contact:
      • Glasgow, United Kingdom
        • Recruiting
        • Beatson West of Scotland Cancer Centre
        • Contact:
        • Principal Investigator:
          • Fieke Froeling
      • Leeds, United Kingdom
        • Recruiting
        • St James' University Hospital
        • Contact:
        • Principal Investigator:
          • Alan Anthoney
      • London, United Kingdom
        • Recruiting
        • Royal Free Hospital
        • Principal Investigator:
          • Roopinder Gillmore
        • Contact:
      • London, United Kingdom
        • Recruiting
        • University College London Hospitals NHS Foundation Trust
        • Principal Investigator:
          • John Bridgewater
        • Contact:
      • London, United Kingdom
        • Recruiting
        • Guy's and St Thomas' NHS Foundation Trust
        • Principal Investigator:
          • Debashis Sarker
        • Contact:
      • Manchester, United Kingdom
        • Recruiting
        • The Christie
        • Contact:
        • Principal Investigator:
          • Mairead McNamara
      • Milton Keynes, United Kingdom
        • Recruiting
        • Milton Keynes University Hospital
        • Principal Investigator:
          • Wasiru Saka
        • Contact:
      • Norwich, United Kingdom
        • Recruiting
        • Norfolk and Norwich University Hospital
        • Principal Investigator:
          • Daniel Holyoake
        • Contact:
      • Nottingham, United Kingdom
        • Recruiting
        • Nottingham University Hospitals NHS Foundation Trust
        • Principal Investigator:
          • Arvind Arora
        • Contact:
      • Plymouth, United Kingdom
        • Recruiting
        • Derriford Hospital
        • Contact:
        • Principal Investigator:
          • Dominique Parslow
    • Cambridgeshire
      • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
        • Recruiting
        • Addenbrooke's Hospital
        • Principal Investigator:
          • Bristi Basu
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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
    • Total bilirubin <1.5 x ULN
  • Adequate renal function defined as a calculated creatinine clearance by Cockcroft - Gault of ≥50 mL/min

Exclusion Criteria:

  • 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
    • Has myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML.
  • Women who are pregnant, or plan to become pregnant or are lactating.
  • Women of child-bearing potential and male patients who are unwilling to adhere to the contraception requirement from informed consent until the last dose of the trial treatment and for 120 days after the last dose of trial treatment.
  • Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the trial medication.
  • Concomitant use of known potent CYP3A4 inhibitors and inducers. Restrictions relating to concomitant medications are described in section 10.9. Please consider wash-out periods.
  • Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to screening.
  • Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
  • Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
  • Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
  • Participant received colony-stimulating factors (e.g., granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM CSF] or recombinant erythropoietin) within 28 days prior to the first dose of study intervention.
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
  • Participant has persistent toxicities (>CTCAE Grade 2) caused by previous cancer therapy, excluding alopecia.
  • Has had an allogenic tissue/solid organ transplant
  • Judgment by the Investigator that the patient should not participate in the trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pembrolizumab and olaparib

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.
Drug: Pembrolizumab
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.
Other Names:
  • Keytruda
  • MK-3475
Drug: Olaparib
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.
Other Names:
  • Lynparza
  • AZD2281
  • KU-0059436

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: Through study completion, an average of 2 years
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse events (Safety and toxicity)
Time Frame: Through study completion, an average of 2 years
Safety and toxicity using NCI CTCAE version 5.0
Through study completion, an average of 2 years
Duration of Response (DOR)
Time Frame: Through study completion, an average of 2 years
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
Through study completion, an average of 2 years
Progression Free Survival (PSF)
Time Frame: through study completion, a maximum of 2 years
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
through study completion, a maximum of 2 years
Overall survival (OS)
Time Frame: through study completion, a maximum of 2 year
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.
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)
Time Frame: Every 9 weeks during the first 27 weeks and then every 12 weeks until death or maximum of 2 years
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.)
Every 9 weeks during the first 27 weeks and then every 12 weeks until death or maximum of 2 years
European Organisation for Research and Treatment of Cancer Pancreatic Cancer Quality of Life Questionnaire (EORTC PAN26)
Time Frame: Every 9 weeks during the first 27 weeks and then every 12 weeks until death or maximum of 2 years
EORTC PAN26 quality of life questionnaire. Min score 26, maximum score 104. Higher scores equals worse outcomes.
Every 9 weeks during the first 27 weeks and then every 12 weeks until death or maximum of 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cambridge University Hospitals NHS Foundation Trust

Collaborators

National Institute for Health Research, United Kingdom

Investigators

  • Principal Investigator: Pippa Corrie, Cambridge University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 26, 2025

Primary Completion (Estimated)

July 31, 2027

Study Completion (Estimated)

January 1, 2028

Study Registration Dates

First Submitted

June 3, 2021

First Submitted That Met QC Criteria

October 21, 2021

First Posted (Actual)

October 26, 2021

Study Record Updates

Last Update Posted (Estimated)

September 18, 2025

Last Update Submitted That Met QC Criteria

September 16, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PemOla

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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