AzTrials
AzTrials

HER2-positive Advanced Gastric Cancer or Gastroesophageal Junction AdenocarcinomaPhase 2NCT07490990

Disitamab Vedotin Combined With Sintilimab and Multimodal Radiotherapy for HER2-Positive Advanced Gastric Cancer After Second-Line Treatment Failure: A Prospective, Single-Arm Phase II Clinical Trial

A Phase 2 study testing Disitamab vedotin + Sintilimab + Multimodality radiotherapy in people with HER2-positive Advanced Gastric Cancer or Gastroesophageal Junction Adenocarcinoma, run by West China Hospital.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Official record

Search all trials

Trial summary

Patients with HER2-positive advanced gastric cancer who experience disease progression after standard first- and second-line therapies have limited subsequent treatment options. Disitamab vedotin, a novel anti-HER2 antibody-drug conjugate (ADC), has been approved in China for this patient population. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Disitamab vedotin + Sintilimab + Multimodality radiotherapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
No sites listed yet
Study dates
Jun 2026to Dec 2028
Phase
Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age: 18-75 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.
  • Liver function: Child-Pugh class A.
  • Histopathologically confirmed advanced gastric cancer with HER2-positive status, defined as HER2 IHC 2+ or 3+, as determined by central laboratory testing.
  • Failure of or intolerance to standard first-line and second-line treatments.
  • At least one measurable lesion based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). If a lesion has previously received local therapy, it may be considered measurable only when unequivocal disease progression has been confirmed. In addition, patients should have at least two measurable lesions suitable for radiotherapy, separate from the RECIST target lesions whenever feasible.
Show all 30Show fewer
  • Patients with controlled hepatitis B virus (HBV) infection are eligible if they have received anti-HBV therapy for at least 1 month before the first dose of study medication, and have an HBV viral load < 2000 IU/mL (10 000 copies/mL) before the first dose. Patients receiving ongoing anti-HBV therapy must maintain the same regimen throughout the study treatment period.
  • Major organ function must meet the following criteria within 28 days before treatment initiation:
  • 1)Hematological parameters, without blood transfusion within the preceding 14 days: hemoglobin (HB) ≥ 80 g/L; absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; platelet count (PLT) ≥ 80 × 10⁹/L.
  • 2)Biochemical parameters: Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN, or ≤ 5 × ULN in subjects with liver metastasis; Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min.
  • 3)Coagulation parameters: International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN. For subjects on anticoagulant therapy, PT and APTT within the therapeutic range are acceptable.
  • 4)Thyroid function: Normal T3 and T4 levels. (9)Women of childbearing potential must agree to use effective contraception during the study and for 120 days after the last dose of study treatment. A negative serum or urine pregnancy test is required within 7 days before study enrollment.
  • Patients must provide written informed consent before enrollment. Exclusion Criteria
  • History of other malignant tumors within the past 5 years or concurrent other malignancies, except cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, or papillary thyroid carcinoma.
  • History of anaphylaxis or severe hypersensitivity to disitamab vedotin, sintilimab, or any excipients of these drugs.
  • Prior treatment with disitamab vedotin or sintilimab.
  • Patients with symptomatic central nervous system metastases.
  • Patients receiving treatment with a strong CYP3A4 inhibitor within 1 week before enrollment, or treatment with a strong CYP3A4 inducer within 2 weeks before enrollment.
  • Congestive heart failure classified as New York Heart Association (NYHA) functional class III-IV.
  • History of an ischemic cardiovascular event within 1 year before enrollment.
  • Ongoing systemic immunosuppressive therapy.
  • Participation in another interventional clinical trial of investigational medicinal products within 4 weeks before the first dose of study medication.
  • Requirement for systemic corticosteroids, equivalent to > 10 mg prednisone per day, or other immunosuppressive agents within 2 weeks before the first dose of study medication.
  • Administration of an antitumor vaccine or a live attenuated vaccine within 4 weeks before the first dose of study medication.
  • Patients with severe infection within 4 weeks before the first dose of study medication.
  • Active autoimmune disease or history of autoimmune disease and history of immunodeficiency.
  • Active pulmonary tuberculosis, history of active pulmonary tuberculosis within 1 year before enrollment, or history of active pulmonary tuberculosis more than 1 year before enrollment without standard anti-tuberculosis treatment.
  • Active viral hepatitis: HBV DNA ≥ 2000 IU/mL (10 000 copies/mL); or hepatitis C virus (HCV) infection, defined as positive anti-HCV antibody and HCV-RNA above the lower limit of detection of the assay.
  • Known history of psychotropic substance abuse, alcoholism, or illicit drug use.
  • Pregnancy or breastfeeding women.

Who cannot join

None listed.

About this study

Patients with HER2-positive advanced gastric cancer who experience disease progression after standard first- and second-line therapies have limited subsequent treatment options. Disitamab vedotin, a novel anti-HER2 antibody-drug conjugate (ADC), has been approved in China for this patient population. Immune checkpoint inhibitors (ICIs) serve as a core therapeutic modality for advanced gastric cancer; however, treatment discontinuation often occurs due to disease progression or immune-related adverse events, which raises clinical demands for immunotherapy rechallenge. Preclinical and early clinical evidence suggests that disitamab vedotin may remodel the tumor immune microenvironment and generate synergistic anti-tumor activity with PD-1 blockade. Furthermore, multimodal radiotherapy combining low-dose radiotherapy (LDRT) and high-dose hypofractionated radiotherapy (HFRT) can enhance systemic anti-tumor immunity through tumor antigen release and remodeling of the tumor immune microenvironment.

This prospective, multicenter, interventional, single-arm phase II clinical study aims to evaluate the efficacy and safety of disitamab vedotin combined with sintilimab and multimodal radiotherapy in patients with HER2-positive advanced gastric cancer with progression following first- and second-line systemic therapy. Eligible participants will receive protocol-specified disitamab vedotin and sintilimab, followed by multimodal radiotherapy delivered to at least two independent lesions. The primary endpoint is progression-free survival (PFS) assessed according to RECIST v1.1. Secondary endpoints include overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety profile. Exploratory biomarker analyses will be conducted using matched tumor tissue and peripheral blood specimens. A total of 30 participants will be enrolled. This trial is conducted in accordance with the Declaration of Helsinki and relevant Chinese biomedical research regulations. All enrolled patients will provide written informed consent, and the study has obtained ethical approval from the Ethics Committee of West China Hospital, Sichuan University.

Being tested
Disitamab vedotin + Sintilimab + Multimodality radiotherapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Disitamab vedotin + Sintilimab + Multimodality radiotherapyDrug

    Patients receive disitamab vedotin (2.5 mg/kg intravenously every 2 weeks), sintilimab (200 mg intravenously every 2 weeks), combined with multimodal radiotherapy consisting of low-dose radiotherapy (2 Gy × 5 fractions) and hypofractionated radiotherapy (8 Gy × 3 fractions).

Study groups in NCT07490990
Study groupRoleWhat they receive
Disitamab vedotin plus sintilimab combined with multimodal radiotherapyExperimentalNot described
Receives: Drug: Disitamab vedotin + Sintilimab + Multimodality radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival (PFS)

    Time from study enrollment to documented disease progression (per RECIST v1.1) or death from any cause, whichever occurs first. Patients without progression or death will be censored at the last valid tumor assessment.

    Measured: Up to 24 months from enrollment of the last participant

Secondary outcomes (3)

  1. Objective Response Rate (ORR)

    Percentage of participants achieving confirmed complete response (CR) or partial response (PR) according to RECIST v1.1.

    Measured: Up to 24 months from enrollment of the last participant

  2. Disease Control Rate (DCR)

    Percentage of participants achieving confirmed CR, PR, or stable disease (SD) according to RECIST v1.1.

    Measured: Up to 24 months from enrollment of the last participant

  3. Overall Survival (OS)

    Time from study enrollment to death from any cause. Participants alive at data cutoff will be censored at the last follow-up date

    Measured: Up to 36 months from enrollment of the last participant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Mar 2026
  2. Study startJun 2026 (estimated)
  3. Primary completionJun 2028 (estimated)
  4. Study completionDec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07490990
Sponsor's protocol ID
20252707
Status last verified
Jul 2026
First submitted
18 Mar 2026
Last updated
3 Aug 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in