Neoadjuvant pembrolizumab with a watch-and-wait strategy for patients with mismatch repair-deficient or microsatellite instability-high (dMMR/MSI-H) localized colon cancer: a randomized GERCOR G-109 PRODIGE 84 PREMICES phase II trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gercor

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

26 Nov 2025 → ongoing

Decision date (initial)

2025-03-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-509322-22-00

ClinicalTrials.gov

NCT06646445

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The primary objective of the study is to evaluate the rate of success of neoadjuvant pembrolizumab treatment for a watch-and-wait approach (experimental arm) at 6 months after randomization in localized dMMR/MSI-H CRC patients

Secondary objectives 8

1. To evaluate the rate of success at 24 months post-randomization in the experimental arm
2. To evaluate the safety according to NCI-Common Toxicity Criteria of Adverse Events (CTCAE v 5.0) of the experimental strategy
3. To assess survival rates OS at 6, 12, and 24 months in both study arms
4. To assess event-free survival (EFS) at 6, 12, and 24 months in both study arms
5. To assess 30-day postoperative morbidity (the Clavien Dindo classification recommended) for patients operated in both study arms
6. To assess participant-reported symptoms, functioning, and health-related quality of life (HRQoL) using EORTC Core-30 Quality of Life questionnaire (EORTC QLQ-C30) and EORTC Quality of Life Questionnaire - Colorectal Cancer Module 29 (EORTC QLQ-CR29) at baseline, 3, 6, 12, and 24 months for patients in both study arms
7. To assess tumor regression grade (TRG) according to the Becker/ Mandar system and the eight edition of American Joint Committee on Cancer tumor, node, metastasis (AJCC TNM) pathologic staging system in patients randomized in the experimental arm and who underwent surgery
8. 8. To assess endoscopic complete response (eCR)

Conditions and MedDRA coding

localized colon cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Is capable of giving signed and dated informed consent (IC
2. Is aged ≥18 years
3. Has an Eastern Cooperative Oncology Group Performance status (ECOG PS) of 0 or 1
4. Has newly diagnosed, histologically confirmed colonic or upper third rectal adenocarcinoma, NB: material must be available from biopsy done during colonoscopy
5. Has radiological tumor assessment at screening performed within 21 days before inclusion according to RECIST v1.1 by chest, abdomen, and pelvis (TAP-CT) showing resectable localized disease (cT0-4 cN0-2 cM0) and no metastatic or non-surgical disease,
6. Has dMMR and/or MSI-high (MSI-H) tumor status as follows: - loss of expression of ≥1 MMR protein (MLH1, MSH2, MSH6, or PMS2) or a dimeric couple (MLH1 and PMS2 or MSH2 and MSH6) on immunohistochemistry (IHC; using hMLH1, hMSH2, hMSH6, hPMS2 antibodies), - And/or ≥ 3 instable markers by the pentaplex by polymerase chain reaction (PCR) (BAT-25, BAT-26, NR-21, NR-24, and NR-27),
7. Has adequate hematological status, renal, and liver function obtained within 14 days prior to randomization of study treatment
8. Has international normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT) ≤1.5 × ULN, except for the patient on anticoagulant therapy who must have PT-INR-aPTT within therapeutic range is deemed appropriate by the Investigator,
9. A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: a. Is a woman of non-childbearing potential as defined: i/ ≥45 years of age and has not had menses for >1 year, ii/ amenorrhea for <2 years without a hysterectomy and oophorectomy and have a high follicle stimulating hormone (FSH) value in the postmenopausal range upon pre-study (screening) evaluation, iii/ post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound, MRI, or CT scan, b. Has negative pregnancy blood test within 72 hours before the first dose of pembrolizumab, AND c. If woman of childbearing potential (WOCBP), female patient must be willing to use a highly effective form of contraception from screening throughout the study treatment and 4 months after the last dose of pembrolizumab,
10. Male patient is eligible to participate if he agrees to the following during the study treatment and for 4 months after the last dose of pembrolizumab: a. Refrain from donating sperm, b. Must use contraception/barrier as follows: - Agree to use a male condom when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant. -Agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person
11. Provides primary tumor tissue samples (archival or fresh biopsy specimen) acquired during coloscopy together with images (mandatory),
12. Is willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study,
13. Is registered in the National Health Care System (PUMa - Protection Universelle Maladie included).

Exclusion criteria 20

1. Has a tumor that is not readily resectable
2. Has bifocal colorectal adenocarcinoma
3. Locally advanced middle or low rectal cancer (<10 cm from the anal verge on MRI, sagittal slide) staged as cT3/T4 and/or N+ and/or with predictive circumferential margin >2 mm on pretreatment MRI. NB: for rectal cancers, the margin of the tumor relative to the anal margin should be indicated on the endoscopy report
4. Has had major surgical procedure within 4 weeks prior to the first dose of study treatment
5. Has a has pre-existing hemostatic disorder or medical condition requiring chronic anticoagulation that cannot be interrupted for the purpose of study specified tumor resection or endoscopic biopsies
6. Has metastases (stage IV disease)
7. Prior treatment with an anti-PD(L)1, anti-LAG-3, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, including prior therapy with anti-tumor vaccines or other immuno-stimulatory antitumor agents
8. Prior malignancy active within the previous 3 years apart from: i/ locally curable cancers that have been apparently cured (e.g., squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast); ii/ Lynch syndrome-related non-CRC in complete remission for > 1 year
9. Has received treatment with any investigational medicinal product within 28 days prior to study entry,
10. Is human immunodeficiency virus (HIV)-positive with CD4+ cell count <600 cell/ml or detectable viral load
11. Has active hepatitis B virus (HBV, defined as having a positive hepatitis B surface antigen [HBsAg] test) or hepatitis C virus (HCV) prior to inclusion.NB: Patients with past HBV infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen antibody test) are eligible.NB: Patients positive for HCV antibody are eligible only if PCR testing is negative for HCV RNA.
12. Impossibility of submitting to the medical follow-up of the study for geographical, social, or psychiatric illness.
13. Patient under a legal protection regime (guardianship, curatorship, judicial safeguard) or administrative decision or incapable of giving his/her consent
14. Has any history of autoimmune disease including, but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis,NB: History of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.NB: Controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible
15. Has had prior (non-infectious) pneumonitis requiring systemic corticosteroid therapy or has currently pneumonitis
16. Has received any live, attenuated vaccine within 30 days prior to the first dose of study treatment or such administration is anticipated during the study
17. Has had prior allogeneic bone marrow transplantation or prior solid organ transplantation
18. Has received treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 14 days (2 weeks) prior to the first dose of trial treatment or is required to receive systemic immunosuppressive medications during the study. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
19. Ongoing anti-cancer treatment for another cancer (to be discussed with the coordinator in case of hormone therapy in patients with prostate and breast cancer)
20. Known hypersensitivity to any of the excipients of pembrolizumab.NB: L-histidine, L-Histidine Hydrochloride monohydrate, sucrose, polysorbate-80 (E433).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The rate of success of the experimental strategy at 6 months or after two successive colonoscopies (corresponding to timepoint at 6 months from the experimental strategy) following randomization

Secondary endpoints 8

1. The rate of strategy success at 24 months after randomization in the experimental arm
2. Safety (according to NCI CTCAE v 5.0) of experimental strategy
3. 3. OS at 6, 12 and 24 months in both study arms
4. EFS at 6, 12 and 24 months in both study arms
5. 30-day postoperative morbidity (the Clavien Dindo classification15 recommended) in patients operated in both treatment arms
6. Participant-reported symptoms, functioning and HRQoL (EORTC QLQ-C30; EORTC QLQ-CR29) at baseline, 3, 6, 12, and 24 months in both study arms
7. TRG (according to the Becker/Mandar system and the AJCC TNM system),
8. Endoscopic complete response (eCR)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gercor

Sponsor organisation

Gercor

Address

151 Rue Du Faubourg Saint Antoine

City

Paris

Postcode

75011

Country

France

Scientific contact point

Organisation

Gercor

Contact name

Marie Line Garcia Larnicol

Public contact point

Organisation

Gercor

Contact name

Nelly Roldan

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 19 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications