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Colorectal CancerPhase 2PUMANCT05131919

Pembrolizumab for Locally Advanced, Irresectable, Non-metastatic dMMR Colorectal Cancers

A Phase 2 study testing Pembrolizumab in people with Colorectal Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

In this study, the efficacy of pembrolizumab in patients with locally advanced, irresectable dMMR colorectal cancer will be assessed. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer
What is being tested?
Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteNetherlands
Study dates
22 Dec 2022to Jul 2031
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed written informed consent
  • Patients at least 18 years of age
  • Locally advanced, irresectable adenocarcinoma of the colon or rectum, not amenable to surgery, or for which induction therapy is required to reconsider surgery, or where free margins can only be obtained by major extension of the surgical procedure, as defined by one of the following:
  • Invasion of the duodenum, stomach, spleen or pancreatic head, for which major extension of the surgical procedure would be required to obtain free margins, and/or for which the chances of positive resection margins are high
  • Invasion or encasement of major blood vessels (superior mesenteric vessels, iliac vessels, portal vein)
  • Invasion or encasement of the ureter
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  • No signs of distant metastases on CT-scan and physical examination; patients may not be eligible for first-line treatment with pembrolizumab according to SoC
  • Patients may not be eligible for standard of care first-line pembrolizumab for metastatic disease
  • Patients may not be potentially eligible for the NICHE study: patients with primarily resectable disease, for which relatively minor extension of the procedure is required to achieve free margins, such as but not limited to a small bowel segment, abdominal wall
  • ECOG performance status of 0 or 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention
  • Screening laboratory tests must meet the criteria as defined in Table 1 and should be obtained within 10 days prior to the start of study intervention:
  • Absolute neutrophil count (ANC) ≥1500/µL; Platelets ≥100 000/µL; Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L, Creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN; Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN; AST (SGOT) and ALT (SGPT) ≤2.5 × ULN; International normalized ratio (INR) OR prothrombin time (PT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants; Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
  • A male participant must agree to use a contraception as detailed in Appendix 2 of this protocol during the treatment period and for at least 200 days (90 days plus the time required for pembrolizumab to undergo five half-lives) after the last dose of study treatment and refrain from donating sperm during this period.
  • Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to registration (see appendix 2). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • A female participant is eligible to participate if she is not pregnant (see appendix 2), not breastfeeding, and at least one of the following conditions applies:
  • Not a woman of childbearing potential (WOCBP) as defined in appendix 2 OR
  • A WOCBP who agrees to follow the contraceptive guidance in appendix 2 during the treatment period and for at least 120 days (30 days plus the time required for pembrolizumab to undergo five half lives) after the last dose of study treatment.
  • CT-scan must be performed within 28 days prior to registration

Who cannot join

  • Previous treatment with immune checkpoint inhibitors targeting including but not limited to CTLA-4, PD-1 or PD-L1
  • Previous treatment with chemotherapy for the disease under study
  • Prior radiotherapy for the disease under study
  • Prior radiotherapy for other indications than the disease under study within 2 weeks of start of study intervention. Participants must have recovered from al radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
  • History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
  • Allergies and Adverse Drug Reaction
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  • History of allergy to study drug components
  • History of severe hypersensitivity reaction to any monoclonal antibody
  • Intercurrent illnesses, including but not limited to infections, unstable angina pectoris
  • Known history of Human Immunodeficiency Virus (HIV) infection and known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
  • Underlying medical conditions that, in the investigator's opinion, will make the administration of the study drug hazardous or obscure the interpretation of toxicity determination of adverse events
  • Active autoimmune disease requiring systemic treatment in the past 2 years;, or other medical conditions requiring systemic steroid or immunosuppressive medications, Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
  • Diagnosis of immunodeficiency or conditions requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
  • Live vaccines in the 4 weeks prior to inclusion
  • History of uncontrolled medical or psychiatric illness
  • Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
  • Current pregnancy or breastfeeding
  • Active malignancies other than disease under study within 3 years prior to inclusion, except for malignancies with a negligible recurrence rate (e.g. <10% in 5 years)
  • Allogenic tissue/solid organ transplant.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Netherlands Cancer Institute

    Amsterdam, 1066 CX

Other trials in Netherlands

About this study

Official title: Pembrolizumab for Locally Advanced, Irresectable, Non-metastatic dMMR Colorectal Cancers. The PUMA Study

In this study, the efficacy of pembrolizumab in patients with locally advanced, irresectable dMMR colorectal cancer will be assessed.

Read the detailed description

In this single-center, single arm, open-label, phase II study assessing the efficacy of pembrolizumab in patients with locally advanced, irresectable dMMR colorectal cancer, 25 patients will be enrolled. All patients will be treated with pembrolizumab 200 mg intravenously on day 1 of each 3-week cycle.

Being tested
Pembrolizumab
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Also called Keytruda

    Treatment with pembrolizumab 200 mg intravenously on day 1 of each 3-week cycle. Treatment will be continued for a maximum duration of 2 years, or until the tumor becomes resectable.

Study groups in NCT05131919
Study groupRoleWhat they receive
pembrolizumabExperimentalTreatment with pembrolizumab 200 mg.
Receives: Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To assess the efficacy of pembrolizumab in patients with locally advanced, irresectable dMMR colorectal cancers by objective response rate (ORR)

    ORR according to RECIST 1.1 criteria

    Measured: 2.5 years

Secondary outcomes (4)

  1. To assess the major pathological response (MPR) in patients undergoing surgery

    MPR is defined as < 10% residual viable tumor

    Measured: 2.5 years

  2. To find biomarkers and evaluation strategies able to accurately assess complete and near-complete responses in order to pursue organ-sparing treatment

    Association between changes in circulating tumor (ct)DNA and complete and near-complete responses, and risk of relapse

    Measured: 2.5 years

  3. In case of surgery, to assess post-surgical outcome and infectious complications following neoadjuvant immunotherapy

    Post-surgical outcome will be assessed by pathologic evaluation, infection complications will be graded according to CTCAE V5.0

    Measured: 2.5 years

  4. To assess the date of relapse

    As determined by disease recurrence or disease-related death during follow-up after surgery

    Measured: 2.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Nov 2021
  2. Study start22 Dec 2022
  3. Primary completionJul 2030 (estimated)
  4. Study completionJul 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Single arm, open-label
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05131919
Sponsor's protocol ID
N21PMA
Acronym
PUMA
Status last verified
Dec 2025
First submitted
2 Nov 2021
Last updated
9 Dec 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab in people with Colorectal Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 9 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To assess the efficacy of pembrolizumab in patients with locally advanced, irresectable dMMR colorectal cancers by objective response rate (ORR) (time frame: 2.5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05131919.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2025.

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