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Localized Resectable TumorPhase 2IMHOTEPNCT04795661

Immunotherapy in MSI/dMMR Tumors in Perioperative Setting.

A Phase 2 study testing Pembrolizumab in people with Localized Resectable Tumor and MSI/dMMR, run by Centre Leon Berard at 18 sites in France.

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

This trial is a multicenter, 3-cohort, prospective, Phase II trial conducted in patients with untreated resectable MSI/dMMR carcinomas and aiming to evaluate the safety and the efficacy of ICI (immune checkpoint inhibitor) as neoadjuvant treatment in these patients. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Localized Resectable Tumor, MSI/dMMR
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
240 participants
Where
18 sitesFrance
Study dates
18 Oct 2021to Oct 2029
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

  • I1. Age ≥ 18 years on the day of signing informed consent.
  • I2. Histologically proven localized non-metastatic tumor included in one of the 4 cohorts:
  • Colon or rectal Cancer (cT3/T4 N0 M0 ou cT N+ M0) OR
  • Oesogastric (gastric, gastro-oesophageal or oesophageal) cancer (cT2 to cT4 N M0) OR
  • Other tumor types (cT2 to cT4 N M0): small bowel adenocarcinoma (duodenum, jejunum, ileum).
  • I3. MSI/dMMR established by immunohistochemistry (IHC) [MMR protein expression] and polymerase chain reaction (PCR) (or Next-Generation Sequencing (NGS)) [both techniques are required] and validated by coordinator's team.
Show all 38Show fewer
  • MMR and/or MSI tumors will be assessed using IHC with four antibodies (anti-MLH1, anti-MSH2, anti-MSH6 and anti-PMS2) and PCR (pentaplex panel is recommended: BAT-25, BAT-26, NR-21, NR-24, and NR-27) prior to screening. Loss of MLH1 and PMS2 / or MSH2 and MSH6 / or MSH6 alone / or PMS2 alone protein staining by IHC indicates dMMR, and tumor with ≥ 2 unstable markers analyzed on PCR proves MSI/dMMR, NGS will be accepted instead of PCR analysis.
  • I4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 to 1 within 7 days prior to the inclusion.
  • I5. Adequate bone-marrow, hepatic, and renal functions, within 10 days prior to the start of study treatment with:
  • Hemoglobin ≥ 9 g/dl or ≥ 5.6 mmol/l, neutrophils ≥ 1.0 x 109/l, platelets ≥ 100 x 109/l,
  • Creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 30 ml/min/1.73m² using either MDRD or CKD-EPI formula,
  • AST and ALT ≤ 3 x ULN, total bilirubin ≤ 1.5 ULN (or direct bilirubin ≤ ULN for patients with total bilirubin >1.5 × ULN),
  • International normalized ratio (INR) OR prothrombin time (PT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants.
  • I6. Covered by a medical/health insurance.
  • I7. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
  • I8. Patients of childbearing potential accepting to use effective contraceptive measures or abstain from heterosexual activity, for the course of the study through 4 months after the last dose of pembrolizumab MK-3475 adjuvant treatment or 6 months after adjuvant chemotherapy or being surgically sterile. Refer to Appendix 1 for approved methods of contraception.
  • I9. Signed and dated IRB/IE approved informed consent form.
  • Non-inclusion criteria
  • E1. MSS/pMMR tumors.
  • E2. Metastatic disease (stage IV).
  • E3. HIV positive with CD4 count under 400 cells/mm3
  • E4.Concurrent active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] positive and/or detectable HBV DNA) or Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection).
  • E5. Active systemic autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg. thyroxine, insulin) is not considered a form of systemic treatment and is allowed.
  • E6. Interstitial lung disease.
  • E7. Prior (non-infectious) pneumonitis requiring systemic corticosteroid therapy or current pneumonitis.
  • E8. History of severe hypersensitivity to another monoclonal antibody.
  • E9. Receiving immunosuppressive therapy or having received corticosteroids (in dosing exceeding 10 mg daily of prednisone equivalent) within the last 2 months before inclusion.
  • E10. Active infections.
  • E11. Radiotherapy within the 2 weeks before inclusion. Patients 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. - Not applicable
  • E12. Live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
  • E13. Known history of active TB (Bacillus Tuberculosis).
  • E14. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
  • E15. Pregnant or breastfeeding woman or patient expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 4 months after the last dose of study treatment.
  • E16. Patient requiring tutorship or curatorship.
  • E17. Ongoing anti-cancer treatment for another cancer (to be discussed with the coordinator in case of hormone therapy).
  • E18. Prior history of other malignancies (except for HNPCC or Lynch syndrome-related cancers) unless the subjects has been free of the disease for at least 2 years.
  • E19. Patient hospitalized at the moment of inclusion and treatment initiation (palliative care unit, retirement home … are considered as hospitals).
  • E20. Recent hemorrhage (in the month before inclusion).

Who cannot join

None listed.

Trial locations and contacts

18 sites in 1 country.

18 sites in 1 country

France18 sites

  • CHU Amiens Picardie

    Amiens, 80054

  • CHU Clermont-Ferrand

    Clermont-Ferrand, 63003

  • Centre Georges-Francois Leclerc

    Dijon, 21079

  • Hopital Huriez

    Lille, 59037

  • Centre Léon Bérard

    Lyon, 69008

  • Institut Paoli Calmettes

    Marseille, 13273

  • Institut du Cancer Val d'Aurelle

    Montpellier, 34298

  • Centre Antoine Lacassagne

    Nice, 06189

  • APHP Hôpital Saint-Louis

    Paris, 75010

  • Institut mutualiste Montsouris

    Paris, 75014

  • Hôpital Européen Georges Pompidou

    Paris, 75015

  • APHP - Hôpital Saint-Antoine

    Paris, 75571

  • Groupe Hospitalier Diaconesses Croix Saint-Simon

    Paris, 75571

  • CHU Poitiers

    Poitiers, 86021

  • Centre Eugène Marquis

    Rennes, 35042

  • CHU Saint Etienne

    Saint-Etienne, 42270

  • Centre Paul Strauss

    Strasbourg, 67200

  • Institut de cancérologie Strasbourg Europe

    Strasbourg, 67200

Other trials in France

About this study

This trial is a multicenter, 3-cohort, prospective, Phase II trial conducted in patients with untreated resectable MSI/dMMR carcinomas and aiming to evaluate the safety and the efficacy of ICI (immune checkpoint inhibitor) as neoadjuvant treatment in these patients.

We hypothesize that immune checkpoint inhibitors (ICPi) will benefit to MSI/dMMR tumors from the early stages, whatever their anatomical origin. We assume that this neoadjuvant treatment would improve the response rate, providing even high rate of pathological complete responses and prolong patients survival.

We anticipated colorectal and gastric cancers to be the most frequent recruited and constructed our statistical hypothesis with results in those 2 cancers. However patients with other localized MSI/dMMR tumors could be included.

Read the detailed description

TREATMENT PLAN:

Pre-operative pembrolizumab will be administered intravenously (IV) over 30 minutes at the dose of 400 mg according to recent summary of product characteristics (SPC). Until four doses will be administered 6 weeks before the planned surgery, as close as possible to inclusion, and whenever possible during standard visit (surgery, anesthesia or other).

Surgery will be performed during the 6th week after the last pembrolizumab injection, as per standard practices.

An adjuvant treatment will be administered upon the Investigator decision, depending on the protocol: the results and tolerance of pre-operative treatment and ability of the patient to receive the treatment regarding his general post-operative condition.

STATISTICAL ANALYSIS:

A total of 240 patients will be enrolled in this study

Sample size was thus evaluated by analogy with an A'Hern's single stage phase II design with P0=25%, P1=50% and 85% power.

A sequential Bayesian design will be used to allow continuous monitoring of the primary endpoint and update knowledge gradually.

For each cohort, interim analyses are planned after 6-week follow up of the first 10 patients (i.e. after surgery) and then every 10 patients.

Early stopping will be recommended if there is a high posterior probability (≥90%) given observed data that the rate of pathological response is lower than 50%.

DATA ENTRY, DATA MANAGEMENT AND STUDY MONITORING:

All the data concerning the patients will be recorded in the electronic case report form (eCRF) throughout the study. Serious adverse event (SAE) and Adverse Event of Specific Interest (AESI) reporting will be also paper-based by e-mail and/or Fax.

The sponsor will perform the study monitoring and will help the investigators to conduct the study in compliance with the clinical trial protocol, Good Clinical Practices (GCP) and local law requirements.

Being tested
Pembrolizumab
Keywords
Oncology, MSI/dMMR status, Pembrolizumab, Immunotherapy, Phase II, Neoadjuvant treatment
Medical subject headings
Neoplasms

What participants receive

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

  • PembrolizumabDrug

    Also called MK3475 - Keytruda®

    Administered intravenous (IV)

Study groups in NCT04795661
Study groupRoleWhat they receive
Cohort Colorectal cancer (CRC)ExperimentalPembrolizumab prior to surgery
Receives: Drug: Pembrolizumab
Cohort Oesogastric cancerExperimentalPembrolizumab prior to surgery
Receives: Drug: Pembrolizumab
Cohort Other cancerExperimentalPembrolizumab prior to surgery
Receives: Drug: Pembrolizumab

What is being measured

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

  1. Rate of complete pathological response (pCR) after surgery

    A complete pathological response will be defined as 0% viable tumor cells.

    Measured: 6 weeks after first injection

Secondary outcomes (12)

  1. Safety of the perioperative treatment

    Safety profile, determined using the National Cancer Institute - Common Terminology Criteria for Adverse Event (NCI-CTC AE) grading scale version 5. Adverse events will be described by their intensity and severity

    Measured: 60 Months (over the whole study)

  2. Rate of surgical complications (post-operative morbidity)

    The rate of surgical complications (post-operative morbidity) will be assessed according to modified Clavien Dindo scoring

    Measured: 1 Month after sugery

  3. Rate of patients with the R0 resection

    Percentage of patients with the R0 resection

    Measured: 60 Months

  4. Major pathological response rate

    Percentage of patients with major pathological response (≤ 10% residual viable tumor)

    Measured: 60 Months

  5. Recurrence-free survival (RFS)

    RFS defined as the time from the date of first study treatment administration to the date of first documented recurrence

    Measured: 60 Months

  6. Overall response rate (ORR) at 4, 10, 16 and 21 weeks after the pembrolizumab initiation

    Percentage of patients with objective response at week 4, 10, 16 and 21 (complete or partial response) after neoadjuvant pembrolizumab, according to RECIST v1.1.

    Measured: 4, 10, 16, 21 weeks after first study treatment injection

  7. Rate of second cancer in the Lynch syndrom spectrum

    Percentage of patients with second cancer

    Measured: 60 Months

  8. The overall survival (OS)

    OS, defined from the date of first study treatment administration to the date of death due to any cause.

    Measured: From 60 months

  9. Progression-free survival (PFS) after recurrence

    PFS, defined from the date of first documented recurrence to the date of documented progression.

    Measured: 60 months

  10. Quality of life (QoL)

    QoL, assessed using the EORTC QLQ-C30

    Measured: Baseline,cycle 2 and 4 before surgery and 5 months after the surgery

  11. The prognostic value of lung immune prognostic index (LIPI)

    Measured: 60 months

  12. the progression free survival for patient without surgery

    PFS, defined from the date of first documented recurrence to the date of documented progression.

    Measured: 60 months

Timeline

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

  1. First posted12 Mar 2021
  2. Study start18 Oct 2021
  3. Primary completion5 Oct 2023
  4. Study completionOct 2029 (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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
240 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04795661
Sponsor's protocol ID
IMHOTEP (ET20-093)
Acronym
IMHOTEP
Status last verified
Sep 2026
First submitted
11 Mar 2021
Last updated
10 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • de la Fouchardiere C, Zaanan A, de Montfort A, Cohen R, Le Sourd S, Tougeron D, Soularue E, Dubreuil O, Williet N, Samalin-Scalzi E, Piessen G, Hautefeuille V, Jary M, Ben Abdelghani M, Evesque L, Rochigneux P, Blanc E, Perol D, Bibeau F, Coutzac C. Efficacy of Perioperative Pembrolizumab in Mismatch Repair Deficient/Microsatellite Unstable Localized Colorectal Cancers: Results of the Phase II Trial IMHOTEP. J Clin Oncol. 2026 Jun;44(16):1520-1528. doi: 10.1200/JCO-25-02169. Epub 2026 Apr 14.

    PubMed 41980235

  • Klute KA, Shah MA. Evolving Therapeutics for Resectable Esophageal Adenocarcinoma. J Natl Compr Canc Netw. 2025 May;23(5):e257044. doi: 10.6004/jnccn.2025.7044.

    PubMed 40340830

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab in people with Localized Resectable Tumor and MSI/dMMR, run by Centre Leon Berard at 18 sites in France.

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 38 inclusion and 0 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 10 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in France. 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?

Rate of complete pathological response (pCR) after surgery (time frame: 6 weeks after first injection). 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 NCT04795661, which also lists 2 linked publications.

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 10 Sep 2026; AzTrials last refreshed its copy on 6 Nov 2026.

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