Testing Immunotherapy (Atezolizumab) With or Without Chemotherapy in Locoregional MSI-H/dMMR Gastric and Gastroesophageal Junction (GEJ) Cancer

Running, not enrolling · Phase 2

Conditions studied: Clinical Stage I Gastric Cancer AJCC v8, Clinical Stage I Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage II Gastric Cancer AJCC v8, Clinical Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage III Gastric Cancer AJCC v8, Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage IVA Gastric Cancer AJCC v8, Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8, Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma

In brief

This phase II trial compares atezolizumab in combination with chemotherapy (docetaxel, oxaliplatin, leucovorin calcium, fluorouracil, capecitabine) to atezolizumab alone for controlling the growth and/or spreading of the disease in patients with gastric or gastroesophageal junction (JEG) cancer that has not spread from where it first started (local) or only has spread to nearby lymph nodes or tissue (locoregional) and has high microsatellite instability (MSI-H) and mismatch repair deficiency (dMMR). The mismatch repair (MMR) system in the body corrects errors made during the copying of DNA and serves as a proofreading function. If this system isn't working correctly, mutations (changes) in DNA occur which can allow the cancer to grow or spread. This is called dMMR (deficient mismatch repair) . MSI-H describes cancer cells that have a high number of mutations within microsatellites. For example, microsatellite testing that shows mutations in 30% or more microsatellites is called microsatellite instability-high (MSI-H). Microsatellites are short, repeated sequences of DNA. There is evidence that MSI-H/ dMMR gastric or GEJ tumors respond well to immunotherapy. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Docetaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It damages the cell's DNA and may kill tumor cells. Capecitabine is in a class of medications called antimetabolites. It is taken up by tumor cells and breaks down into fluorouracil, a substance that kills tumor cells. Chemotherapy drugs such as leucovorin calcium and fluorouracil work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Using atezolizumab as immunotherapy with and following chemotherapy versus atezolizumab alone prior to and after surgery may shrink or stabilize the tumor in patients with MSI-H/dMMR localized gastric or GEJ cancer and may increase the length of time after treatment that cancer does not come back or get worse.

Key facts

Study ID

NCT05836584

Run by

National Cancer Institute (NCI)

People needed

2

Starts

2023-12-06

Expected to finish

2027-06-28

Last updated by the study team

2026-07-01

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patient must be >= 18 years of age
• Patient must have histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma that is MSI-H/dMMR (microsatellite instability-high/mismatch repair deficient) as determined by one of three methods:
• Deficient deoxyribonucleic acid (DNA) mismatch repair protein (MMR) expression status: MMR status must be assessed by immunohistochemistry (IHC) for MMR protein expression (MLH1, MSH2, MSH6, PMS2) where loss of one or more proteins indicates dMMR. dMMR may be determined either locally or by site-selected reference lab by Clinical Laboratory Improvement Act (CLIA)-certified assay
• NOTE: Loss of MLH1 and PMS2 commonly occur together
• Polymerase chain reaction (PCR) determined microsatellite instability
• MSI-H tumor status determined by next-generation sequencing
• Patient must have previously untreated localized gastric, or Siewert type II or III GEJ (gastroesophageal junction) adenocarcinoma. Tumors must be staged as T2 or greater primary lesion or be any T stage with the presence of positive locoregional lymph nodes- N+ (clinical nodes) without evidence of metastatic disease
• Siewert type II tumors: tumors located between 1 cm proximal and 2 cm distal to the GEJ
• Siewert type III tumors: tumors located between 2 and 5 cm distal to GEJ
• Patient must be amenable to surgical resection with therapeutic intent
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count (ANC) >= 1,500/mcL (obtained =< 14 days prior to randomization)
• Platelets >= 100,000/mcL (obtained =< 14 days prior to randomization)
• Hemoglobin >= 9 g/dL (obtained =< 14 days prior to randomization)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) OR direct bilirubin =< ULN (for patients with total bilirubin > 1.5 x ULN) (obtained =< 14 days prior to randomization)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]): x =< 3 institutional ULN (obtained =< 14 days prior to randomization)
• Creatinine =< 1.5 x institutional ULN OR glomerular filtration rate (GFR) > 50 mL/min/1.73m\^2 (obtained =< 14 days prior to randomization)
• Albumin >= 2.5 g/dL (obtained =< 14 days prior to randomization)
• International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN (unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time [PTT] is within therapeutic range of intended use of anticoagulants) (obtained =< 14 days prior to randomization)
• Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants) (obtained =< 14 days prior to randomization)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• Patient must have no contraindications to receive one of the chemotherapy regimens: FLOT or mFOLFOX / CAPOX
• Patient must not have had prior potentially curative surgery for carcinoma of the stomach/GEJ
• Patient must not receive any other standard anti-cancer therapy or experimental agent concurrently with the study drugs
• Patient must have recovered from clinically significant adverse events of their most recent therapy/intervention prior to randomization

Where it is running

• Kaiser Permanente-Fremont — Fremont, California, United States
• Kaiser Permanente-Fresno — Fresno, California, United States
• Kaiser Permanente-Modesto — Modesto, California, United States
• Kaiser Permanente-Oakland — Oakland, California, United States
• Kaiser Permanente-Roseville — Roseville, California, United States
• Kaiser Permanente Downtown Commons — Sacramento, California, United States
• Kaiser Permanente-South Sacramento — Sacramento, California, United States
• Kaiser Permanente-San Francisco — San Francisco, California, United States
• Kaiser Permanente-Santa Teresa-San Jose — San Jose, California, United States
• Kaiser Permanente San Leandro — San Leandro, California, United States
• Kaiser San Rafael-Gallinas — San Rafael, California, United States
• Kaiser Permanente Medical Center - Santa Clara — Santa Clara, California, United States
• Kaiser Permanente-Santa Rosa — Santa Rosa, California, United States
• Kaiser Permanente-South San Francisco — South San Francisco, California, United States
• Kaiser Permanente-Vallejo — Vallejo, California, United States
• Kaiser Permanente-Walnut Creek — Walnut Creek, California, United States
• Beebe South Coastal Health Campus — Millville, Delaware, United States
• Helen F Graham Cancer Center — Newark, Delaware, United States
• Medical Oncology Hematology Consultants PA — Newark, Delaware, United States
• Beebe Health Campus — Rehoboth Beach, Delaware, United States
• Kaiser Permanente Moanalua Medical Center — Honolulu, Hawaii, United States
• Illinois CancerCare-Bloomington — Bloomington, Illinois, United States
• Illinois CancerCare-Canton — Canton, Illinois, United States
• Illinois CancerCare-Carthage — Carthage, Illinois, United States
• Kaiser Permanente Dublin — Dublin, California, United States

Full record on ClinicalTrials.gov

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