A Study of Atezolizumab and Trastuzumab in Combination With Capecitabine and Oxaliplatin in Patients With HER2 Positive Locally Advanced Resectable Gastric Cancer of Adenocarcinoma of Gastroesophageal Junction

NCT04661150 | Active Not Recruiting Phase 2 Results FDA Drug

• 1 other identifier: ML42058
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 8

Brief Summary

This is a phase II, multicenter, randomized, open-label study designed to evaluate the efficacy and safety of perioperative trastuzumab+XELOX with / without atezolizumab in participants eligible for surgery with locally advanced HER2-positive gastric cancer or adenocarcinoma of GEJ.

Conditions

Gastric Cancer; Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Regression (pCR) Rate

  pCR is defined as no evidence of vital residual tumor cells on hematoxylin and eosin evaluation of the complete resected gastric/GEJ specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (NAST), which will be reviewed by local pathologist..

  Completion of neoadjuvant systemic therapy (up to approximately 16 months)

Secondary Outcomes (7)

• Event-free Survival (EFS)

  Randomization to the first documented disease recurrence, unequivocal tumor progression or death from any cause, whichever occurs first (up to approximately 52 months)

• Disease-Free Survival (DFS)

  Surgery to first documented disease recurrence or death from any cause, whichever occurs first (up to approximately 52 months)

• Overall Survival (OS)

  Randomiation to death from any cause (up to approximately 52 months)

• Major Pathologic Response (MPR)

  Randomization up to approximately 16 months

• Objective Response Rate (ORR)

  Randomiation to CR or PR during neoadjuvant systemic therapy (up to approximately 16 months)

Study Arms (2)

Arm A: Atezolizumab plus Trastuzumab with XELOX (Capecitabine + Oxaliplatin)

EXPERIMENTAL

Participants will receive atezolizumab + trastuzumab + XELOX (Capecitabine + Oxaliplatin) for 3 treatment cycles prior to surgery, each cycle is 3 weeks. Following surgery, patrticipants will receive 5 further cycles of this regimen.

Drug: Atezolizumab; Drug: Trastuzumab; Drug: Capecitabine; Drug: Oxaliplatin

Arm B: Trastuzumab with XELOX (Capecitabine + Oxaliplatin)

ACTIVE COMPARATOR

Participants will receive trastuzumab + XELOX (Capecitabine + Oxaliplatin) for 3 treatment cycles prior to surgery, each cycle is 3 weeks. Following surgery, participants will receive 5 further cycles of this regimen.

Drug: Trastuzumab; Drug: Capecitabine; Drug: Oxaliplatin

Interventions

Atezolizumab DRUG

Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle for 3 cycles prior to surgery and 5 cycles after surgery.

Also known as: Tecentriq

Arm A: Atezolizumab plus Trastuzumab with XELOX (Capecitabine + Oxaliplatin)

Trastuzumab DRUG

Trastuzumab will be administered as an 8 mg/kg IV loading dose and then 6 mg/kg IV on Day 1 of a 21-day cycle for 3 cycles before surgery, and administration will continue after surgery. The first administration of trastuzumab after surgery should also be given at the loading dose of 8 mg/kg.

Also known as: Herceptin

Arm A: Atezolizumab plus Trastuzumab with XELOX (Capecitabine + Oxaliplatin); Arm B: Trastuzumab with XELOX (Capecitabine + Oxaliplatin)

Capecitabine DRUG

Capecitabine 1000 mg/m\^2 will be administered twice orally on Days 1-14, repeated every 3 weeks.

Arm A: Atezolizumab plus Trastuzumab with XELOX (Capecitabine + Oxaliplatin); Arm B: Trastuzumab with XELOX (Capecitabine + Oxaliplatin)

Oxaliplatin DRUG

Oxaliplatin 130 mg/m\^2 will be administered by IV on Day 1 of a 21-day cycle.

Arm A: Atezolizumab plus Trastuzumab with XELOX (Capecitabine + Oxaliplatin); Arm B: Trastuzumab with XELOX (Capecitabine + Oxaliplatin)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed gastric cancer or adenocarcinoma of GEJ
• HER2-positive status defined as either IHC score of 3+ or IHC 2+ with amplification proven by in situ hybridization (ISH) as assessed by local review based on pretreatment endoscopic biopsies.
• Clinical stage at presentation: cT3/T4a/T4b, or N+, M0 as determined by AJCC staging system, 8th edition
• Availability of pretreatment tumor specimen for biomarker analysis by central lab
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy \>= 12 weeks
• Adequate hematologic and end-organ function
• For female patients of childbearing potential, agreement (by patient) to remain abstinent (refrain from heterosexual intercourse) or to use highly effective form(s) of contraception during the treatment period and to continue its use for at least i) 5 months after the last dose of atezolizumab, ii) 7 months after the last dose of trastuzumab, or iii) 6 months after the last dose of capecitabine or oxaliplatin, whichever is longer.
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm

You may not qualify if:

• Stage IV (metastatic) or unresectable gastric/GEJ cancer determined by investigators
• Prior systemic therapy for treatment of gastric cancer
• History of malignancy other than GC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
• Cardiopulmonary dysfunction
• Dyspnea at rest
• Active or history of autoimmune disease or immune deficiency with the following exceptions: (a) Patients with a history of autoimmune-mediated hypothyroidism who are on thyroid-replacement hormone are eligible for the study. (b) Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study. (c) Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only are eligible for the study provided allof following conditions are met: (i) Rash must cover \< 10% of body surface area (ii) Disease is well controlled at baseline and requires only low-potency topical corticosteroids (iii) No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
• Active tuberculosis
• Patients with active hepatitis B
• Patients with active hepatitis C

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (8)

Beijing Cancer Hospital

Beijing, 100142, China

Location

West China Hospital, Sichuan University

Chengdu, 610041, China

Location

Nanfang Hospital, Southern Medical University

Guangzhou, 510515, China

Location

Harbin Medical University Cancer Hospital

Harbin, 150081, China

Location

Zhongshan Hospital Fudan University

Shanghai, 200032, China

Location

Liaoning Provincial Cancer Hospital

Shengyang, 110042, China

Location

First Hospital of China Medical University

Shenyang, 110001, China

Location

Tianjin Medical University Cancer Institute & Hospital

Tianjing, 300060, China

Location

Related Publications (2)

• Peng Z, Zhang X, Liang H, Zheng Z, Wang Z, Liu H, Hu J, Sun Y, Zhang Y, Yan H, Tong L, Xu J, Ji J, Shen L. Atezolizumab and Trastuzumab Plus Chemotherapy for ERBB2-Positive Locally Advanced Resectable Gastric Cancer: A Randomized Clinical Trial. JAMA Oncol. 2025 Jun 1;11(6):619-624. doi: 10.1001/jamaoncol.2025.0522.

  PMID: 40244574 DERIVED

• Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore). 2022 May 27;101(21):e29304. doi: 10.1097/MD.0000000000029304.

  PMID: 35623069 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

atezolizumab; Trastuzumab; Capecitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2020
• First Posted: December 10, 2020
• Study Start: March 12, 2021
• Primary Completion: May 8, 2023
• Study Completion (Estimated): July 30, 2026
• Last Updated: April 16, 2026
• Results First Posted: October 17, 2024

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

CN (8)