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

NCT04006262 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: NEONIPIGA - D18-02
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 15

Brief 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.

Conditions

Localized Oesogastric Adenocarcimona; MSI and or dMMR

Outcome Measures

Primary Outcomes (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

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

Secondary Outcomes (6)

• Disease-free survival (DFS)

  Up to 36 months

• Overall Survival (OS)

  Up to 36 months

• Number of participants with treatment-related adverse events

  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.

• Analyze MSI status

  up to 36 months

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

  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)

Study Arms (1)

Experimental arm

EXPERIMENTAL

* Neo-adjuvant treatment (6 cycles - 12 weeks) * Surgery * Adjuvant treatment (9 cycles - 9 months)

Drug: Nivolumab 10 MG/ML; Drug: Ipilimumab 200 MG in 40 ML Injection

Interventions

Nivolumab 10 MG/ML DRUG

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

Also known as: Opdivo

Experimental arm

Ipilimumab 200 MG in 40 ML Injection DRUG

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

Also known as: Yervoy

Experimental arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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)

You may not qualify if:

• 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,
• Metastases (M stage disease) whatever the location,
• Pregnant or breastfeeding women,
• Human immunodeficiency virus (HIV),
• 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,

Sponsors & Collaborators

• GERCOR - Multidisciplinary Oncology Cooperative Group: lead
• Bristol-Myers Squibb: collaborator

Study Sites (15)

CHRU Jean Minjoz

Besançon, France

Location

Hôpital Henri Mondor

Créteil, France

Location

Institut Hospitalier Franco-Britannique

Levallois-Perret, France

Location

CHRU Lille

Lille, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Hôpital Privé Jean Mermoz

Lyon, France

Location

ICM Val d'Aurelle

Montpellier, France

Location

CHU Nantes

Nantes, France

Location

Hôpital Européen Geroges Pompidou

Paris, France

Location

Hôpital Saint Antoine

Paris, France

Location

Hôpital Saint Louis

Paris, France

Location

Institut Mutualiste Montsouris

Paris, France

Location

CHU Poitiers

Poitiers, France

Location

CHU Pontchaillou Rennes

Rennes, 35033, France

Location

CHU Toulouse

Toulouse, France

Location

Related Publications (1)

• 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.

  PMID: 35969830 DERIVED

MeSH Terms

Conditions

Microsatellite Instability

Interventions

Nivolumab; Ipilimumab; Injections

Condition Hierarchy (Ancestors)

Genomic Instability; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Thierry ANDRE, MD

  Hôpital Saint Antoine PARIS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2019
• First Posted: July 5, 2019
• Study Start: October 23, 2019
• Primary Completion: October 1, 2025
• Study Completion: October 1, 2025
• Last Updated: June 15, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (15)