Phase II Study of Trastuzumab Rezetecan Combined With Retlirafusp Alfa With or Without CAPOX as Perioperative Therapy for Resectable Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma

September 2, 2026 updated by: Tianjin Medical University Cancer Institute and Hospital

A Multicenter, Randomized Phase II Study of Trastuzumab Rezetecan Combined With Retlirafusp Alfa With or Without CAPOX Regimen for Perioperative Treatment of Resectable Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

This two-stage, multicenter, randomized open-label phase II trial enrolls untreated resectable stage II-III gastric/gastroesophageal junction adenocarcinoma patients with any HER2 expression. Stage 1 is a safety lead-in cohort of 6 patients receiving Trastuzumab Rezetecan(SHR-A1811)+Retlirafusp alfa(SHR-1701) plus CAPOX to assess dose-limiting toxicity (DLT) within 21 days after initial dosing. If safety risk is acceptable, stage 2 will randomize 74 eligible patients 1:1 into two parallel cohorts stratified by HER2 status. Cohort1 receives perioperative Trastuzumab Rezetecan(SHR-A1811)+Retlirafusp alfa(SHR-1701)+CAPOX; Cohort2 receives dual targeted-immunotherapy without chemotherapy (Trastuzumab Rezetecan+Retlirafusp alfa). All patients undergo D2 radical gastrectomy after neoadjuvant therapy, followed by adjuvant treatment and Retlirafusp alfa(SHR-1701) maintenance up to maximum 17 total cycles. The primary endpoint is pCR rate evaluated by CAP pathological criteria. Secondary endpoints include R0 resection rate, EFS, DFS, OS and perioperative/surgical/systemic safety profiles. Biomarker exploratory analysis will be performed to evaluate the correlation between PD-L1, MSI, TMB and clinical efficacy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Tianjin Municipality
      • Tianjin, Tianjin Municipality, China, 300000
        • Tianjin Medical University Cancer Institute & Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Voluntarily sign written informed consent before any study-related procedures
  2. Age ≥18 and ≤75 years old
  3. Histopathologically confirmed gastric or gastroesophageal junction adenocarcinoma
  4. AJCC 8th edition stage II-III resectable disease (cT1-2N+M0, T3-4aNanyM0); negative peritoneal cytology (CY0) confirmed by pre-study laparoscopy
  5. HER2 expression status: High HER2 (IHC 3+ or IHC 2+ FISH-positive) OR Low/Intermediate HER2 (IHC 2+ FISH-negative / IHC 1+)
  6. No prior systemic anti-tumor therapy (chemotherapy, targeted therapy, immunotherapy, radiotherapy, radical gastrectomy)
  7. Planned radical D2 gastrectomy after neoadjuvant treatment completion
  8. Able to swallow oral capecitabine tablets intact
  9. ECOG Performance Status 0 or 1
  10. Estimated overall survival ≥12 months

  11. Adequate organ function (no blood products/G-CSF within prior 14 days):

    • ANC ≥1.5×10⁹/L; PLT ≥80×10⁹/L; Hb ≥90 g/L
    • Total bilirubin <1.5×ULN; ALT/AST ≤2.5×ULN
    • Serum Cr ≤1.5×ULN or CrCl >50 mL/min
    • INR, PT, APTT ≤1.5×ULN
  12. Fertile female subjects: Negative serum pregnancy test within 72 hours before first dose; all fertile participants agree to effective contraception during treatment and required post-treatment contraceptive window

Exclusion Criteria:

  1. Siewert type I GEJ tumor or Siewert II tumor requiring cervicothoracic surgical approach
  2. Confirmed peritoneal metastasis, positive peritoneal cytology (CY1), or AJCC T4b disease
  3. Tumor unresectable or absolute contraindication to radical gastrectomy
  4. History of other malignant tumor within past 5 years (excluding cured basal cell skin carcinoma, cervical/breast carcinoma in situ)
  5. Uncontrolled hypertension (SBP≥160 mmHg or DBP≥100 mmHg despite optimal medical management)
  6. Cardiac dysfunction: NYHA grade ≥2 heart failure, LVEF <50%, unstable angina, myocardial infarction within 1 year, prolonged QTc interval (male >450ms, female >470ms), family history of sudden cardiac death <40 years old
  7. GI perforation/fistula within 6 months, intestinal obstruction within 3 months (not fully resolved)
  8. Active severe bleeding disorder or active peptic ulcer disease
  9. Arterial/venous thromboembolic event within past 6 months (stroke, DVT, pulmonary embolism etc.)
  10. Severe uncontrolled infection (≥CTCAE grade 2) within 4 weeks prior to first dose
  11. Active viral hepatitis (HBV DNA ≥2000 IU/mL; active HCV viremia) or HIV positive
  12. History or active interstitial lung disease, pulmonary fibrosis, active tuberculosis
  13. Active autoimmune disease requiring long-term systemic immunosuppressive therapy
  14. Systemic corticosteroid dose >10 mg prednisone equivalent within 7 days pre-treatment
  15. Received live attenuated vaccine within 28 days before enrollment
  16. Hypersensitivity to any study drug or excipients
  17. Participation in other interventional clinical trials within 4 weeks prior to first dose
  18. Lactating female subjects
  19. Any medical, psychiatric or social condition judged by investigator to interfere with study compliance or subject safety

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort 1: Trastuzumab Rezetecan + Retlirafusp alfa + CAPOX Perioperative Therapy + Retlirafusp Alfa
Drug: Trastuzumab Rezetecan + Retlirafusp alfa + CAPOX
  1. Drug: Trastuzumab Rezetecan Description: IV infusion Q3W; Cycle 1 loading dose 6.4 mg/kg, subsequent cycles 4.8 mg/kg; administered for 3 neoadjuvant cycles and 3 adjuvant cycles
  2. Drug: Retlirafusp alfa Description: IV infusion 1800 mg Q3W; 3 neoadjuvant, 3 adjuvant cycles, then single-agent maintenance up to total 17 cycles
  3. Drug: Oxaliplatin Description: 60 mg/m² IV Q3W, only 3 neoadjuvant cycles
  4. Drug: Capecitabine Description: 750 mg/m² oral twice daily, 2 weeks on / 1 week off; 3 neoadjuvant + 3 adjuvant cycles
  5. Procedure: Radical D2 Gastrectomy Description: R0 curative resection performed 3-6 weeks post final neoadjuvant dose
Experimental: Cohort 2: Trastuzumab Rezetecan + Retlirafusp Alfa (Without Chemotherapy) Perioperative Therapy + Re
Drug: Trastuzumab Rezetecan + Retlirafusp Alfa
  1. Drug: Trastuzumab Rezetecan Description: IV infusion Q3W; Cycle 1 loading dose 6.4 mg/kg, subsequent cycles 4.8 mg/kg; administered for 3 neoadjuvant cycles and 3 adjuvant cycles
  2. Drug: Retlirafusp alfa Description: IV infusion 1800 mg Q3W; 3 neoadjuvant, 3 adjuvant cycles, then single-agent maintenance up to total 17 cycles
  3. Procedure: Radical D2 Gastrectomy Description: R0 curative resection performed 3-6 weeks post final neoadjuvant dose

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Pathological Complete Response (pCR)
Time Frame: after surgery，within approximately 4-6 weeks
Proportion of subjects achieving CAP Tumor Regression Grade 0 (TRG0), defined as no viable malignant cells detected in primary gastric tumor and all regional lymph nodes after radical D2 gastrectomy
after surgery，within approximately 4-6 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
R0 Resection Rate
Time Frame: within approximately 2 weeks after surgery
The proportion of subjects who achieve R0 resection confirmed by postoperative surgical pathology.
within approximately 2 weeks after surgery
Event-Free Survival (EFS)
Time Frame: Up to 5 years
EFS is the time from date of randomization until the date of disease progression or death.(assessed by the investigator per RECIST v1.1 criteria)
Up to 5 years
Overall Survival (OS)
Time Frame: Up to 5 years
Overall survival is length of time from randomization until the date of death due to any cause.
Up to 5 years
Incidence, severity and causality of TEAEs, SAEs graded by NCI-CTCAE 6.0.
Time Frame: From first study drug to 90 days after last drug administration
Assessment of safety
From first study drug to 90 days after last drug administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tianjin Medical University Cancer Institute and Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 30, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 30, 2031

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 19, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 2, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 3, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 2, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • E20260976

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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