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Localized Oesogastric AdenocarcimonaPhase 2NEONIPIGANCT04006262

Pre-operative Nivolumab and Ipilimumab, Followed by Post-operative Nivolumab, for MSI/dMMR Oeso-gastric Adenocarcinoma.

A Phase 2 study testing Nivolumab 10 MG/ML and Ipilimumab 200 MG in 40 ML Injection in people with Localized Oesogastric Adenocarcimona and MSI and or dMMR, run by GERCOR - Multidisciplinary Oncology Cooperative Group at 15 sites in France.

Active, not recruiting

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

Official record
Search all trials

Trial summary

This is a non-randomized study, open label phase II study. The purpose of this study is to evaluate the complete pathologic response rate (cPRR) with neoadjuvant nivolumab and ipilimumab combination in patients with MSI and/or dMMR localized oeso-gastric cancer. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Nivolumab 10 MG/ML and Ipilimumab 200 MG in 40 ML Injection
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
15 sitesFrance
Study dates
23 Oct 2019to Oct 2025
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 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed and dated informed consent,
  • Age ≥18 years to ≤75 years of age,
  • Histologically proven non-metastatic gastric adenocarcinoma or of the oeso-gastric junction T2 to T4, Nx, M0 after thoraco-abdominopelvic computed tomography (CT) and echo-endoscopy,
  • Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study,
  • dMMR (protein expression by immunohistochemistry [ICH] and/or MSI by polymerase chain reaction [PCR]), MMR and/or MSI tumors should be assessed per local guidelines: ICH with two (anti-MLH1 and anti-MSH2 or anti-MSH6, and antiPMS2) or four antibodies (anti-MLH1, anti-MSH2, anti-MSH6, and anti-PMS2) and/or PCR (with PROMEGA: BAT- 25, BAT-26, NR-21, NR-24, and NR-27) by the investigators prior to screening, Extinct MLH1 (+/- PMS2), MSH2 (+/- MSH6), MSH6, or PMS2 alone protein expression by IHC (dMMR), and/or tumor with ≥ 2 instable MSI-H markers on PCR: BAT25, BAT26, NR21, NR24, and NR27 (pentaplex panel is recommended),
  • The Eastern Cooperative Oncology Group Performance status (ECOG PS) 0-1, for patients over 70 years ECOG PS of 0;
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  • Hematological status: absolute neutrophil count (ANC) ≥1.5 x 109/L; platelets ≥100 x 109/L; hemoglobin ≥9 g/dL,
  • Adequate renal function: serum creatinine level <120 µM, clearance > 50ml/min (Modification of the Diet in Renal Disease [MDRD] or Cockcroft and Gault),
  • Adequate liver function: serum bilirubin ≤1.5 x upper normal limit (ULN), alkaline phosphatase <5 x ULN, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3.0 x ULN,
  • No prior therapy for localized oeso-gastric cancer,
  • Radiological tumor assessment within 21 days before the start of treatment according to RECIST version 1.1 by Chest Abdomen and Pelvis CT,
  • For female patients of childbearing potential, negative pregnancy test within 7 days before starting the study drug,
  • Men and women are required to use adequate birth control during the study (when applicable), Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use a highly effective method of birth control (i.e., pregnancy rate of less than 1% per year) during the period of treatment and during 5 and 7 months, woman and men, respectively, from the last treatment administration. Men must refrain from donating sperm during this same period, Contraceptive methods that result in a low failure rate when used consistently and correctly include methods such as combined hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), some intrauterine devices, intrauterine hormone- releasing stem, true sexual abstinence (when this is in line with the preferred and usual lifestyle of the participant), bilateral tubal occlusion, or a female partner who is not of childbearing potential or a male partner who has had a vasectomy. Women and female partners using hormonal contraceptive must also use a barrier method i.e. condom or occlusive cap (diaphragm or cervical/vault caps), A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (>12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus),
  • Subject willing to comply to provide primary tumor tissue (archival or fresh biopsy specimen), including possible pre-treatment biopsy for PD-L1 expression analysis and other biomarker correlative studies
  • Registration in a National Health Care System (PUMa - Protection Universelle Maladie included)

Who cannot join

  • Non-eligible to clinical trial if one of following parameter is reported:
  • Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),
  • Treatment with any investigational medicinal product within 28 days prior to study entry,
  • Major surgical procedure within 4 weeks prior to initiation of study treatment,
  • Other serious and uncontrolled non-malignant disease (including active infection),
  • Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years,
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  • Metastases (M stage disease) whatever the location,
  • Pregnant or breastfeeding women,
  • Human immunodeficiency virus (HIV),
  • Active hepatitis B virus (HBV, defined as having a positive hepatitis B surface antigen [HBsAg] test prior to inclusion) or hepatitis C virus (HCV). Note: 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. Note: Patients positive for HCV antibody are eligible only if PCR testing is negative for HCV RNA
  • Patient on tutelage or guardianship or under the protection of justice.
  • Impossibility of submitting to the medical follow-up of the study for geographical, social or psychiatric reasons.
  • Non-eligible to immunotherapy:
  • 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, Note: History of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible. Note: Controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible.
  • History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest imaging,
  • Administration of a live, attenuated vaccine within 4 weeks prior to start of treatment or anticipation that such a live attenuated vaccine will be required during the remainder of the study,
  • Prior treatment with CD137 agonists, anti-CTLA4, anti-PD-1, or antiPD-L1 therapeutic antibody or pathway-targeting agents,
  • Prior allogeneic bone marrow transplantation or prior solid organ transplantation,
  • 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 2 weeks prior to start of adjuvant treatment, or requirement for systemic immunosuppressive medications during the remainder of the study. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Note: Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled into the study after approval of the Medical Contact. Subjects are permitted the use of topical, ocular, intra- articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption).
  • Adrenal replacement steroid doses including doses >10 mg daily prednisone is permitted. A brief (less than 3 weeks) course of corticosteroids for prophylaxis (e.g. contrast dye allergy) or for treatment of non-autoimmune conditions (e.g. delayed-type hypersensitivity reaction caused by a contact allergen) is permitted

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

France15 sites

  • CHRU Jean Minjoz

    Besançon

  • Hôpital Henri Mondor

    Créteil

  • Institut Hospitalier Franco-Britannique

    Levallois-Perret

  • CHRU Lille

    Lille

  • Centre Léon Bérard

    Lyon, 69373

  • Hôpital Privé Jean Mermoz

    Lyon

  • ICM Val d'Aurelle

    Montpellier

  • CHU Nantes

    Nantes

  • Hôpital Européen Geroges Pompidou

    Paris

  • Hôpital Saint Antoine

    Paris

  • Hôpital Saint Louis

    Paris

  • Institut Mutualiste Montsouris

    Paris

  • CHU Poitiers

    Poitiers

  • CHU Pontchaillou Rennes

    Rennes, 35033

  • CHU Toulouse

    Toulouse

Other trials in France

About this study

Official title: Peri-operative Association of Immunotherapy (Pre-operative Association of Nivolumab and Ipilimumab, Post-operative Nivolumab Alone) in Localized Microsatellite Instability (MSI) and/or Deficient Mismatch Repair (dMMR) Oeso-gastric Adenocarcinoma: An Open-label GERCOR Phase II Study

This is a non-randomized study, open label phase II study. The purpose of this study is to evaluate the complete pathologic response rate (cPRR) with neoadjuvant nivolumab and ipilimumab combination in patients with MSI and/or dMMR localized oeso-gastric cancer.

Read the detailed description

In patients with resectable oeso-gastric adenocarcinoma, radical surgery is the only curative option. Despite the evolution in treatment with multimodality treatment strategies, oeso-gastric cancer remains one of the most lethal malignancies with 5-year survival rates reaching only 22%. When the disease is localized, perioperative chemotherapy with cytotoxic agents is the preferred strategy since it increases the overall survival (OS) rate. However, in oeso-gastric cancers with microsatellite instability (MSI), is a favorable prognostic factor, the recommended cytotoxic chemotherapy combination seems inefficient and even deleterious.

It is now well established that dMMR and or the MSI phenotype are the surrogate markers of response to immunotherapy.

The combination of nivolumab and ipilimumab had shown promising efficacy in multiple tumor types (dMMR/MSI).

Based on the data above, we have designed this phase II study to evaluate the complete pathological response rate (cPRR) in patients with non-metastatic MSI/dMMR oeso-gastric adenocarcinoma treated with neoadjuvant nivolumab and ipilimumab treatment.

Being tested
Nivolumab 10 MG/ML, Ipilimumab 200 MG in 40 ML Injection
Medical subject headings
Microsatellite Instability

What participants receive

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

  • Nivolumab 10 MG/MLDrug

    Also called Opdivo

    Neo-adjuvant treatment : 240 mg intravenous (I.V.) in 30 minutes - every 2 weeks - 6 cycles

    • Adjuvant treatment : 480mg I.V. in 30 minutes - every 4 weeks - 9 cycles

  • Ipilimumab 200 MG in 40 ML InjectionDrug

    Also called Yervoy

    Neo-adjuvant treatment : 1mg/kg over 30 minutes every 6 cycles - 2 cycles

Study groups in NCT04006262
Study groupRoleWhat they receive
Experimental armExperimental* Neo-adjuvant treatment (6 cycles - 12 weeks) * Surgery * Adjuvant treatment (9 cycles - 9 months)
Receives: Drug: Nivolumab 10 MG/ML; Drug: Ipilimumab 200 MG in 40 ML Injection

What is being measured

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

  1. Complete pathological response (cPRR) rate

    Each center will assess the pathologic response with a centralized center review in case of cPRR and the analysis will be in intention-to-treat (ITT).

    cPRR will be defined as complete tumor disappearance of tumor in the low esophagus or the stomach (from 1/3 inferior of the esophagus to pylorus) after surgery anatomopathologic examination according to mandard scale.

    Surgery will be performed within 5 weeks +\- 1 week after the last cycle (cycle 6) of neoadjuvant therapy

    Measured: time point when the tumor is examined after the surgery (up to 30 months)

Secondary outcomes (6)

  1. Disease-free survival (DFS)

    DFS is defined as the time from the date of starting treatment to local recurrence and/or metastases or death irrespective of cause and censored at the date of last contact.

    Measured: Up to 36 months

  2. Overall Survival (OS)

    OS is defined as the time between the date of the first dose of study treatment and the death date. Patients alive at last report will be considered censored at the endpoint. Alive patients will be censored at the last date known to be alive, either during study treatment period or during follow-up period.

    Measured: Up to 36 months

  3. Number of participants with treatment-related adverse events

    Number of participants with treatment-related adverse events as assessed by National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] v5.0

    Measured: Patients will be assessed for AEs throughout the study at every visit during treatment and at 3-month follow-up visit (3 months after treatment ends). Investigators using the NCI-CTCAE version 5.0 will grade the severity of AEs.

  4. Analyze MSI status

    Confirmation of MSI and/or dMMR has to be confirmed retrospectively on archival or fresh tumor FFPET block from the primary tumor obtained at the time of the initial diagnosis

    Measured: up to 36 months

  5. Quantification of antigen-specific CD4+ T cells as biomarker of anti-PD1/PDL1 immunotherapy in dMMR tumors

    Quantification of antigen-specific CD4+ T cells as biomarker of anti-PD1/PDL1 immunotherapy in blood of dMMR tumors.

    Measured: Blood samples at baseline, C3D1 and C6D1 of neoadjuvant therapy - cycle every 2 weeks, after surgery at C1 D1(first cycle of adjuvant treatment) and at the end of treatment visit (28 days after the last dose of treatment (up to 36 months)

  6. Number of Species of bacteria and yeast composition

    To investigate the microbiota composition changes during neoadjuvant therapy with nivolumab and ipilimumab and its relation to response and/or chemotoxicity.

    Number of Species of bacteria and yeast will be quantitfy and identify. Number of Change of composition will be investigate based on baseline samples compared to 12 weeks sample.

    DNA will be extracted from fecal samples taken prior to therapy and on-treatment (week 12). A gene sequencing approach will be utilized to survey microbial species in the gut in order to define microbiota as a function of the efficacy and safety.

    Measured: Baseline and at week 12

Timeline

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

  1. First posted5 Jul 2019
  2. Study start23 Oct 2019
  3. Primary completionOct 2025 (estimated)
  4. Study completionOct 2025 (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
Masking
None (open label)
Enrolment
32 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04006262
Sponsor's protocol ID
NEONIPIGA - D18-02
Acronym
NEONIPIGA
Status last verified
Jun 2025
First submitted
17 Jun 2019
Last updated
15 Jun 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Samaille T, Henriques J, Tougeron D, Piessen G, de la Fouchardiere C, Louvet C, Adenis A, Jary M, Garcia-Larnicol ML, Cohen R, Vernerey D, Lefevre JH, Svrcek M, Andre T. Nivolumab-Ipilimumab for Localized Microsatellite Instability-High Gastric/Gastroesophageal Junction Adenocarcinoma: The Phase 2 NEONIPIGA Nonrandomized Clinical Trial. JAMA Oncol. 2026 Oct 15:e264162. doi: 10.1001/jamaoncol.2026.4162. Online ahead of print.

    PubMed 42879140

  • Andre T, Tougeron D, Piessen G, de la Fouchardiere C, Louvet C, Adenis A, Jary M, Tournigand C, Aparicio T, Desrame J, Lievre A, Garcia-Larnicol ML, Pudlarz T, Cohen R, Memmi S, Vernerey D, Henriques J, Lefevre JH, Svrcek M. Neoadjuvant Nivolumab Plus Ipilimumab and Adjuvant Nivolumab in Localized Deficient Mismatch Repair/Microsatellite Instability-High Gastric or Esophagogastric Junction Adenocarcinoma: The GERCOR NEONIPIGA Phase II Study. J Clin Oncol. 2023 Jan 10;41(2):255-265. doi: 10.1200/JCO.22.00686. Epub 2022 Aug 15.

    PubMed 35969830

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab 10 MG/ML and Ipilimumab 200 MG in 40 ML Injection in people with Localized Oesogastric Adenocarcimona and MSI and or dMMR, run by GERCOR - Multidisciplinary Oncology Cooperative Group at 15 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 15 inclusion and 21 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 15 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 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?

Complete pathological response (cPRR) rate (time frame: time point when the tumor is examined after the surgery (up to 30 months)). 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 NCT04006262, 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 15 Jun 2025.

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