Conversion Therapy With RC48, Sintilimab, and SOX for HER2 1+/2+ Unresectable Gastric Cancer

NCT07194005 | Recruiting Phase 2

• 1 other identifier: RCVDTYPEC092
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the efficacy of disitamab vedotin in combination with sintilimab and SOX as conversion therapy in patients with initially unresectable locally advanced or metastatic gastric cancer exhibiting HER2 IHC 1+/2+ expression. The trial plans to enroll patients with a single initial unresectable factor and HER2 IHC 1+/2+ status. Participants will receive disitamab vedotin combined with sintilimab and SOX for 4 to 6 treatment cycles. Those who achieve successful conversion will undergo surgical resection, while patients with unsuccessful conversion will either continue the original regimen or switch to an alternative treatment at the investigator's discretion.

Conditions

Gastric Cancer

Keywords

gastric cancer; disitamab vedotin; conversion therapy

Outcome Measures

Primary Outcomes (1)

• R0 resection rate

  Defined as no residue under the microscope after resection

  Within 1 month of surgery

Secondary Outcomes (5)

• Pathologic complete response

  Within 1 month of surgery.

• Overall survival

  2 years from the start of system therapy.

• 1/2-year survival rate

  1/2 years from the start of system therapy.

• Adverse events(all grades）

  From the start of system therapy to 6 months after surgery.

• Serious adverse events(≥grade 3）

  From the start of system therapy to 6 months after surgery.

Study Arms (1)

Conversion therapy

EXPERIMENTAL

Drug: Disitamab Vedotin in combination with sintilimab and SOX

Drug: Disitamab vedotin(RC48); Drug: Sintilimab; Drug: S-1; Drug: Oxaliplatin

Interventions

Disitamab vedotin(RC48) DRUG

2.5 mg/kg, administered intravenously every 3 weeks (Q3W) on Day 1 of each cycle.

Also known as: RC48

Conversion therapy

Sintilimab DRUG

200 mg, administered intravenously, d1, every 3 weeks.

Conversion therapy

S-1 DRUG

Oral, 40-60 mg, twice daily (bid), d1-14, every 3 weeks.

Also known as: Tegafur Gimeracil Oteracil Potassium Capsule

Conversion therapy

Oxaliplatin DRUG

130 mg/m², administered intravenously on Day 1 (d1), every 3 weeks.

Conversion therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily enrolled and provided written informed consent;
• Aged 18-70 years (inclusive), male or female;
• Histologically and/or cytologically confirmed unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma;
• No prior systemic anticancer therapy;
• HER2 immunohistochemistry (IHC) result of 2+ or 1+, based on either previous test results (confirmed by the investigator) or central laboratory assessment;
• Presence of a single initial unresectable factor;
• At least one measurable lesion per RECIST 1.1;
• Life expectancy ≥ 6 months;
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1;
• Adequate organ function, defined as follows:
• Hematological (within 14 days prior to screening, without transfusion or granulocyte colony-stimulating factor \[G-CSF\] support):
• Hemoglobin ≥ 90 g/L;
• Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L;
• White blood cell count ≥ 3.0 × 10⁹/L;
• Platelet count ≥ 80 × 10⁹/L;

You may not qualify if:

• History of malignancies other than gastric cancer, with the following exceptions:
• Malignancies treated with curative intent and with no evidence of disease for 5 years;
• Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, superficial bladder cancer, cervical carcinoma in situ, or other in situ carcinomas.
• Conditions affecting the absorption, distribution, metabolism, or excretion of the investigational drug(s) (e.g., severe vomiting, chronic diarrhea, intestinal obstruction, malabsorption, etc.).
• Previous allogeneic stem cell or solid organ transplantation.
• Prior systemic antitumor therapy (including Chinese herbal medicine with antitumor indications) completed less than 4 weeks before the first dose of study treatment, or with prior treatment-related adverse events not recovered to ≤ CTCAE grade 1 (except for alopecia or pigmentation).
• History or presence of congenital or acquired immunodeficiency disorders.
• Active or previously documented autoimmune or inflammatory disorders (including but not limited to autoimmune hepatitis, interstitial pneumonia, inflammatory bowel disease, systemic lupus erythematosus, vasculitis, uveitis, hypophysitis, hyperthyroidism, hypothyroidism, asthma requiring bronchodilators, etc.). Patients with vitiligo, childhood asthma that has fully resolved without intervention in adulthood, or other conditions deemed eligible by the investigator may be included.
• Use of systemic immunosuppressive therapy within 2 weeks prior to enrollment, or anticipated need for such therapy during the study, with the following exceptions:
• Intranasal, inhaled, topical, or local corticosteroid injections (e.g., intra-articular);
• Systemic corticosteroids at a dose ≤ 10 mg/day prednisone or equivalent;
• Prophylactic corticosteroids for hypersensitivity reactions.
• Known or suspected history of hypersensitivity to disitamab vedotin, anti-PD-1 agents, chimeric or humanized antibodies or fusion proteins, or any excipient of the investigational drug(s).
• History of thrombotic or thromboembolic events within the past 6 months, such as stroke and/or transient ischemic attack, deep vein thrombosis, pulmonary embolism, etc.
• Patients assessed by the physician to be at significant risk of bleeding, including but not limited to:

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200230, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

sintilimab; S 1 (combination); Oxaliplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Central Study Contacts

Xiaowen Liu

CONTACT

18017317145; liuxw1129@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Gastric Surgery

Model Details: Disitamab vedotin in combination with sintilimab and SOX as conversion therapy

Study Record Dates

• First Submitted: September 18, 2025
• First Posted: September 26, 2025
• Study Start: September 4, 2025
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2028
• Last Updated: September 26, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)