A Study of Disitamab Vedotin, Tunlametinib, and PD-1 Antibody for Advanced Gastric Cancer

NCT07507526 | Not Yet Recruiting Phase 2

• 1 other identifier: SYSUCC-HER2
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if the combination of disitamab vedotin, tunlametinib, and a PD-1 antibody works to treat HER2-overexpressing advanced gastric cancer in patients who have already received at least two lines of prior therapy. It will also learn about the safety of this combination therapy. The main questions it aims to answer are: What is the objective response rate (tumor shrinkage) in participants receiving this combination? What medical problems (side effects) do participants have when taking this combination? Researchers will evaluate the efficacy and safety of disitamab vedotin combined with tunlametinib and a PD-1 antibody in patients with HER2-overexpressing advanced gastric cancer who have failed at least two lines of standard treatment. Participants will: Receive disitamab vedotin intravenously every 2 weeks and a PD-1 antibody intravenously once every 6 weeks. Take tunlametinib orally every 12 hours. Continue treatment until disease progression or unacceptable toxicity. Visit the clinic every 2 weeks for checkups, blood tests, and safety monitoring. Undergo tumor imaging assessments every 6 weeks to evaluate treatment response.

Conditions

Gastric Adenocarcinoma

Keywords

HER2 overexpression; HER2-ADC; MEK; immunotherapy

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  Objective response rate is defined as the proportion of participants who achieve a best overall response of either complete response (CR) or partial response (PR) according to irRECIST (immune-related Response Evaluation Criteria in Solid Tumors) criteria.

  Up to approximately 24 months

Secondary Outcomes (2)

• Overall survival

  Up to 24 months after last patient enrollment

• Progression free survival

  Up to approximately 24 months

Study Arms (1)

DTP

EXPERIMENTAL

Disitamab vedotin (RC48): 2.5 mg/kg intravenously on Day 1 of each 14-day cycle Tislelizumab: 400 mg intravenously on Day 1 of each 42-day cycle Tunlametinib: Orally every 12 hours at the dose determined during the safety run-in phase

Drug: Tunlametinib+PD-1 mAb

Interventions

Tunlametinib+PD-1 mAb DRUG

Disitamab vedotin (RC48): 2.5 mg/kg intravenously on Day 1 of each 14-day cycle Tislelizumab: 400 mg intravenously on Day 1 of each 42-day cycle Tunlametinib: Orally every 12 hours at the dose determined during the safety run-in phase

Also known as: Disitamab vedotin

DTP

Eligibility Criteria

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

You may qualify if:

• Patients with advanced gastric cancer who have received at least two lines of prior systemic therapy or are intolerant to standard therapy; HER2 immunohistochemistry (IHC) 2+ or 3+; Presence of measurable target lesions according to irRECIST criteria; Expected survival of at least 3 months; Age ≥ 18 years, male or female;
• Adequate organ function meeting the following requirements:
• White blood cell count (WBC) ≥ 3.0 × 10⁹/L, absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L;
• Platelet count ≥ 75 × 10⁹/L;
• Hemoglobin ≥ 9 g/dL;
• Serum albumin ≥ 2.8 g/dL;
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN), ALT, AST, and/or ALP ≤ 2.5 × ULN;
• Serum creatinine ≤ 1.5 × ULN or creatinine clearance \> 60 mL/min; Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1; Ability to understand the study and provide written informed consent.

You may not qualify if:

• Known or suspected hypersensitivity to the investigational drugs. Dysphagia. Female patients who are pregnant or breastfeeding. Patients who have received disitamab vedotin in first- or second-line treatment.
• Inability to provide informed consent due to psychological, family, social, or other factors.
• Severe impairment of cardiac, pulmonary, hepatic, or renal function; hematopoietic system disorders; cachexia; or other conditions that preclude tolerability of drug therapy.
• Autoimmune diseases or history of autoimmune diseases (e.g., colitis, hepatitis, hyperthyroidism, including but not limited to these diseases or syndromes); history of immunodeficiency, including positive HIV test, or other acquired or congenital immunodeficiency diseases; history of organ transplantation or allogeneic bone marrow transplantation.
• Patients requiring systemic corticosteroids (\>10 mg/day prednisone equivalent) or other immunosuppressive medications within 14 days prior to the first dose or during the study period. However, the following circumstances are permitted for enrollment: topical or inhaled steroids, or adrenal hormone replacement therapy at a dose ≤10 mg/day prednisone equivalent, in the absence of active autoimmune disease.
• History of interstitial lung disease or non-infectious pneumonitis.
• Active pulmonary tuberculosis infection identified by medical history or CT scan, or history of active pulmonary tuberculosis infection within 1 year prior to enrollment, or history of active pulmonary tuberculosis infection more than 1 year prior to enrollment without appropriate treatment.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Shanghai Kechow Pharma, Inc.: collaborator
• BeOne Medicines: collaborator
• RemeGen Co., Ltd.: collaborator

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Interventions

disitamab vedotin

Central Study Contacts

Miaozhen Qiu, MD, PhD

CONTACT

8602087343351; qiumzh@sysucc.org.cn

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: Professor

Study Record Dates

• First Submitted: March 26, 2026
• First Posted: April 2, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2028
• Last Updated: April 2, 2026

Record last verified: 2026-03

Locations

CN (1)