Neoadjuvant SHR-A1811 and SHR-A1701 ± Pertuzumab for Potentially Immunotherapy-Sensitive GC or GEJ Adenocarcinoma

NCT07716111 | Not Yet Recruiting Phase 2

• 1 other identifier: ART-HER2-2
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-center, randomized controlled phase II clinical trial.It plans to enroll a total of 24 eligible patients with locally advanced gastric/gastroesophageal junction adenocarcinoma who are HER2-positive and have potential benefit from immunotherapy (PD-L1 CPS≥1, EBV-positive, or dMMR/MSI-H). All patients were randomly assigned to the following two groups in a 1:1 ratio. Group A:Trastuzumab Rezatecan Dosage: 4.8 mg/kg, intravenous infusion Frequency: Once every 3 weeks (Q3W) Retlirafusp alfa (SHR-1701) Dosage: 30 mg/kg, intravenous infusion Frequency: Once every 3 weeks (Q3W) Group B: Trastuzumab Rezatecan Dosage: 4.8 mg/kg, intravenous infusion Frequency: Once every 3 weeks (Q3W) Retlirafusp alfa (SHR-1701) Dosage: 30 mg/kg, intravenous infusion Frequency: Once every 3 weeks (Q3W) Pertuzumab biosimilar (Betta Pharma): 840mg at first usage; subsequent maintenance: 420mg per dose,Q3W The neoadjuvant treatment phase will consist of 4 cycles, with each cycle lasting 21 days, for a total treatment duration of approximately 12 weeks. Imaging examinations will be performed after 2 cycles. Preoperative Assessment and Surgery Within 4 weeks after the completion of neoadjuvant therapy, patients will undergo imaging examinations for surgical feasibility assessment. Those eligible for surgery will undergo radical gastrectomy (D2 lymphadenectomy) 4-6 weeks after the last dose. The endpoints are efficacy and safety, specifically including: Primary Endpoint: pCR rate (the percentage of subjects achieving pathological complete response, defined as the absence of residual viable tumor cells in the primary tumor bed); Secondary Endpoints: MPR rate (the percentage of subjects achieving major pathological response, defined as ≤10% residual viable tumor cells in the tumor bed); EFS (Event-Free Survival, defined as the time from the initiation of treatment to the first occurrence of any of the following events: disease progression precluding surgical resection, local or distant recurrence, or death from any cause); R0 resection rate (defined as macroscopically tumor-free surgical margins and microscopically negative tumor cells within 1 mm of the surgical margin); OS (Overall Survival, defined as the time from the start date of neoadjuvant therapy to death from any cause or the date of the last follow-up). Safety: The incidence rates of adverse events (AE) and serious adverse events (SAE) and their correlation with the treatment. Exploratory Endpoints: Infiltration status of immune cell subsets in tumor tissue before and after treatment.

Conditions

Gastric or Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Complete pathological response (pCR) rate

  The percentage of subjects achieving pathological complete response, defined as the absence of residual viable tumor cells in the primary tumor bed.

  assessed within 4 weeks post-surgery

Secondary Outcomes (5)

• Major Pathological Response (MPR)

  from preoperative to 7 days postoperative

• EFS (Event-Free Survival)

  2 years after surgery

• R0 resection rate

  from preoperative to 7 days postoperative

• OS (Overall Survival)

  2 years after surgery

• adverse events (AEs)

  From enrollment to the end of treatment at 12 weeks

Other Outcomes (1)

• Exploratory Endpoints

  From the first administration of the drug to 2 years after the surgery

Study Arms (2)

control group

ACTIVE COMPARATOR

Trastuzumab Rezatecan Dosage: 4.8 mg/kg, intravenous infusion Frequency: Once every 3 weeks (Q3W) Retlirafusp alfa (SHR-1701) Dosage: 30 mg/kg, intravenous infusion Frequency: Once every 3 weeks (Q3W)

Drug: Trastuzumab Rezatecan and Retlirafusp alfa

Experimental group

EXPERIMENTAL

Trastuzumab Rezatecan Dosage: 4.8 mg/kg, intravenous infusion Frequency: Once every 3 weeks (Q3W) Retlirafusp alfa (SHR-1701) Dosage: 30 mg/kg, intravenous infusion Frequency: Once every 3 weeks (Q3W) Pertuzumab biosimilar (Betta Pharma):840mg, subsequent maintenance: 420mg per dose,Q3W

Drug: Trastuzumab Rezatecan and Retlirafusp alfa+Pertuzumab

Interventions

Trastuzumab Rezatecan and Retlirafusp alfa DRUG

Trastuzumab Rezatecan Dosage: 4.8 mg/kg, intravenous infusion Frequency: Once every 3 weeks (Q3W) Retlirafusp alfa (SHR-1701) Dosage: 30 mg/kg, intravenous infusion Frequency: Once every 3 weeks (Q3W)

control group

Trastuzumab Rezatecan and Retlirafusp alfa+Pertuzumab DRUG

Trastuzumab Rezatecan Dosage: 4.8 mg/kg, intravenous infusion Frequency: Once every 3 weeks (Q3W) Retlirafusp alfa (SHR-1701) Dosage: 30 mg/kg, intravenous infusion Frequency: Once every 3 weeks (Q3W) Pertuzumab biosimilar (Betta Pharma):840mg, subsequent maintenance: 420mg per dose,Q3W

Experimental group

Eligibility Criteria

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

You may qualify if:

• Voluntary Participation: The subject voluntarily agrees to participate in this study, is able to sign the informed consent form (ICF), and has good compliance.
• Age and Gender: Aged 18 to 75 years (at the time of signing the ICF), regardless of gender.
• Diagnosis and Staging: Histologically and/or cytologically confirmed gastric cancer or gastroesophageal junction adenocarcinoma. Diagnosed as locally advanced according to the AJCC 8th Edition criteria, with cTNM staged as T3-4N+M0 based on endoscopic ultrasound or contrast-enhanced CT/MRI scans (combined with diagnostic laparoscopy if necessary). The subject must agree to undergo radical surgery, and the investigator assesses the lesion as potentially resectable.
• Treatment History: No prior systemic therapy for the current disease, including anti-tumor radiotherapy, chemotherapy, or immunotherapy.
• HER2 Status: Confirmed HER2 IHC 3+ or HER2 IHC 2+ with positive FISH result based on endoscopic biopsy tissue IHC results.
• Biomarker Status: PD-L1 CPS ≥1, EBV-positive, or dMMR/MSI-H; at least one of the three criteria must be met.
• Performance Status: ECOG score of 0-1.
• Life Expectancy: Estimated life expectancy ≥6 months.
• Organ Function: Adequate major organ function
• Contraception and Pregnancy: Subjects of childbearing potential must use appropriate contraception methods during the study and for 120 days after the end of the study. Serum pregnancy test must be negative within 7 days prior to study enrollment, and the subject must not be breastfeeding.

You may not qualify if:

• Other Malignancies: Concomitant malignant diseases other than gastric cancer (excluding early-stage tumors that have been radically cured).
• Bleeding Risk: Tumor lesions with a tendency to bleed (e.g., active ulcerative tumor lesions with positive fecal occult blood test, history of hematemesis or melena within 2 months prior to signing the ICF, or judged by the investigator to be at risk of massive gastrointestinal bleeding) or have received blood transfusion therapy within 4 weeks prior to the administration of the study drug.
• Concurrent Studies: Currently participating in other interventional drug clinical studies, or have received other investigational drugs or investigational device therapy within 4 weeks prior to the first dose.
• Prior Therapies: Previous exposure to the following therapies: anti-HER2, anti-PD-1, anti-PD-L1 agents, anti-PD-L2 agents, or drugs targeting another stimulatory or co-inhibitory T-cell receptor (including but not limited to CTLA-4, OX-40, CD137, etc.).
• Autoimmune Disease: Active autoimmune disease that required systemic treatment (e.g., use of disease-modifying agents, corticosteroids, or immunosuppressants) within 2 years prior to the first dose.
• Note: The use of physiological doses of corticosteroids (≤10 mg/day prednisone or equivalent) is permitted. Replacement therapies (e.g., thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are not considered systemic treatment.
• Prior Medication: Received systemic treatment with Traditional Chinese Medicines with anti-tumor indications or drugs with immunomodulatory effects (including thymosin, interferon, interleukins, excluding local use for pleural effusion control) within 2 weeks prior to the first dose.
• Transplant History: Known history of allogeneic organ transplantation (excluding corneal transplantation) or allogeneic hematopoietic stem cell transplantation.
• Allergy: Known hypersensitivity to the drugs used in this study.
• Neuropathy: Peripheral neuropathy ≥ Grade 2.
• HIV Infection: Known history of Human Immunodeficiency Virus (HIV) infection (i.e., HIV 1/2 antibody positive).
• Hepatitis: Subjects with active Hepatitis B or Hepatitis C.
• Vaccination: Received live vaccines within 30 days prior to the first dose (Cycle 1, Day 1).
• Note: Inactivated virus vaccines for seasonal influenza (injection) are permitted within 30 days prior to the first dose; however, live attenuated influenza vaccines administered intranasally are not permitted.
• Pregnancy/Lactation: Pregnant or breastfeeding women.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

First Affiliated Hospital of Nanjing Medical Unviersity

Nanjing, Jiangsu, 210000, China

Location

Central Study Contacts

Hao XU

CONTACT

86-2568306505; liuhongda@njmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This is a randomized controlled study design, planning to enroll a total of 24 eligible patients with locally advanced gastric/gastroesophageal junction adenocarcinoma who are HER2-positive and have potential benefit from immunotherapy (PD-L1 CPS≥1, EBV-positive, or dMMR/MSI-H). All patients were randomly assigned to the following two groups in a 1:1 ratio. Group A:Trastuzumab Rezatecan Dosage: 4.8 mg/kg, intravenous infusion Frequency: Once every 3 weeks (Q3W) Retlirafusp alfa (SHR-1701) Dosage: 30 mg/kg, intravenous infusion Frequency: Once every 3 weeks (Q3W) Group B: Trastuzumab Rezatecan Dosage: 4.8 mg/kg, intravenous infusion Frequency: Once every 3 weeks (Q3W) Retlirafusp alfa (SHR-1701) Dosage: 30 mg/kg, intravenous infusion Frequency: Once every 3 weeks (Q3W) Pertuzumab biosimilar (Betta Pharma): 840mg, subsequent maintenance: 420mg per dose,Q3W

Study Record Dates

• First Submitted: July 16, 2026
• First Posted: July 21, 2026
• Study Start: July 16, 2026
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2029
• Last Updated: July 21, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)