A Study of Disitamab Vedotin Combined With Trastuzumab and Tislelizumab Versus Chemotherapy Combined With Trastuzumab With or Without Pembrolizumab in HER2-high Expression Advanced Gastric or Gastroesophageal Junction Adenocarcinoma.

RemeGen

Status and phase: Enrolling; Phase 3

Conditions: Gastric Carcinoma

Treatments: Drug: Pembrolizumab; Drug: CAPOX (oxaliplatin/capecitabine); Drug: Tislelizumab; Drug: Disitamab Vedotin; Drug: Trastuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT07315750

RC48-C040

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy and safety of Disitamab Vedotin combined with Trastuzumab and Tislelizumab Versus Chemotherapy Combined with Trastuzumab with or without Pembrolizumab as First-Line Treatment for Advanced Gastric/Gastroesophageal Junction Adenocarcinoma with HER2-high Expression.

Enrollment: 555 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Voluntarily consent to participate in the study and sign the informed consent form
• Expected survival period >12 weeks
• ECOG Performance Status 0 or 1
• Histologically confirmed unresectable locally advanced or metastatic --gastric/gastroesophageal junction adenocarcinoma
• No prior systemic therapy for locally advanced or metastatic gastric cancer; or disease progression or recurrence occurring ≥6 months after completion of neoadjuvant/adjuvant therapy
• HER2-high expression
• At least one assessable lesion according to RECIST v1.1 criteria
• Adequate organ function
• Female subjects of childbearing potential must have a negative blood pregnancy test within 7 days prior to the first treatment, and agree not to breastfeed or donate ova from the signing of the informed consent form until 6 months after the last treatment. Male subjects must agree not to donate sperm from the signing of the informed consent form until 6 months after the last treatment.
• Able to understand the study requirements and willing to comply with the study and follow-up procedures

Exclusion criteria

• Presence of central nervous system (CNS) metastasis and/or carcinomatous meningitis
• Peripheral neuropathy > Grade 1
• Tumor lesions with a tendency to bleed
• Severe gastrointestinal dysfunction that may affect drug intake, transport, or absorption
• Bone metastases with a risk of paraplegia
• Past or current interstitial lung disease, or severely impaired lung function
• Other malignancies within 5 years prior to randomization, except for those expected to be cured with treatment
• Pregnant or breastfeeding women

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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555 participants in 2 patient groups

Disitamab Vedotin Combined with Trastuzumab and Tislelizumab

Experimental group

Description:

Participants will receive Disitamab Vedotin, Trastuzumab and Tislelizumab until the occurrence of intolerable toxicity, disease progression (investigator-assessed), initiation of new anti-tumor therapy, loss to follow-up, withdrawal of informed consent, or death (whichever occurs first).

Treatment:

Drug: Trastuzumab

Drug: Disitamab Vedotin

Drug: Tislelizumab

Chemotherapy (CAPOX) Combined with Trastuzumab With or Without Pembrolizumab

Active Comparator group

Description:

Participants will receive CAPOX, Trastuzumab and Trastuzumab. Only subjects whose PD-L1 expression is confirmed as CPS ≥1 by the central laboratory will receive pembrolizumab. Treatment will continue until the occurrence of intolerable toxicity, disease progression (investigator-assessed), initiation of new anti-tumor therapy, loss to follow-up, withdrawal of informed consent, or death (whichever occurs first).

Treatment:

Drug: Trastuzumab

Drug: Pembrolizumab

Drug: CAPOX (oxaliplatin/capecitabine)