Gastric AdenocarcinomaPhase 2DTP-HER2NCT07507526
A Study of Disitamab Vedotin, Tunlametinib, and PD-1 Antibody for Advanced Gastric Cancer
A Phase 2 study testing Tunlametinib+PD-1 mAb in people with Gastric Adenocarcinoma, run by Sun Yat-sen University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastric Adenocarcinoma
- What is being tested?
- Tunlametinib+PD-1 mAb
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 1 siteChina
- Study dates
- Apr 2026to 30 Apr 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 510060
Miaozhen Qiu, MD, PhD, 8602087343351, qiumzh@sysucc.org.cn
Miao-Zhen Qiu, MD, PhD
About this study
Official title: A Study on the Efficacy and Safety of Disitamab Vedotin Combined With Tunlametinib and PD-1 Antibody in Third-Line and Above Treatment of Patients With HER2-Overexpressing Advanced Gastric Cancer
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:
Read more
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.
Read the detailed description
This is an open-label, single-arm, phase II clinical trial evaluating the efficacy and safety of disitamab vedotin (RC48) in combination with tunlametinib and a PD-1 antibody (tislelizumab) in patients with HER2-overexpressing advanced gastric cancer who have failed at least two lines of prior systemic therapy.
Background HER2-overexpressing gastric cancer accounts for approximately 12-23% of advanced gastric cancer cases. Disitamab vedotin, a novel anti-HER2 antibody-drug conjugate (ADC) conjugated with the microtubule inhibitor MMAE, has demonstrated an objective response rate (ORR) of 24.8% and a median overall survival (OS) of 7.9 months in third-line treatment of HER2-overexpressing advanced gastric cancer (C008 study). However, primary and acquired resistance to ADC monotherapy remains a significant clinical challenge. Preclinical studies by the study team have shown that MAPK-ERK pathway inhibition with MEK inhibitors can upregulate HER2 expression, enhance lysosomal activity, and synergistically augment the antitumor activity of HER2-ADCs both in vitro and in vivo. The combination of a MEK inhibitor with disitamab vedotin and a PD-1 antibody has demonstrated synergistic effects in humanized mouse models.
Study Design The study consists of a safety run-in phase followed by an expansion phase. The safety run-in phase will evaluate three dose levels of tunlametinib (6 mg, 9 mg, and 12 mg orally every 12 hours) in combination with fixed doses of disitamab vedotin (2.5 mg/kg intravenously every 2 weeks) and tislelizumab (400 mg intravenously every 6 weeks) to determine the recommended dose for the expansion phase.
Following determination of the recommended dose, the expansion phase will enroll additional patients to further evaluate the efficacy and safety of the triplet combination.
Treatment Regimen
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
Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-specified discontinuation criteria are met. Tumor assessments will be performed every 6 weeks ± 3 days using enhanced CT or MRI according to irRECIST criteria.
Study Objectives
Primary Objectives: To evaluate the objective response rate (ORR) and safety profile of the combination therapy
Secondary Objectives: To evaluate progression-free survival (PFS), overall survival (OS), and quality of life
Exploratory Objectives
To analyze HER2 protein expression and immune cell infiltration in pre-/post treatment tumor tissue samples
To assess changes in serum cytokine levels before and after treatment
To characterize gut microbiota composition using 16S and metagenomic sequencing of fecal samples collected at baseline, first efficacy assessment, and disease progression.
- Conditions
- Gastric Adenocarcinoma
- Being tested
- Tunlametinib+PD-1 mAb
- Keywords
- HER2 overexpression, HER2-ADC, MEK, immunotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tunlametinib+PD-1 mAbDrug
Also called Disitamab vedotin
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Tunlametinib+PD-1 mAb |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to approximately 24 months
Secondary outcomes (2)
Overall survival
Time from first dose of study treatment to death from any cause. Participants alive at the time of analysis will be censored at the last known alive date. Kaplan-Meier method will be used to estimate median OS with 95% confidence intervals.
Measured: Up to 24 months after last patient enrollment
Progression free survival
Progression-free survival is defined as the time from the first dose of study treatment to the date of first documented disease progression per irRECIST criteria or death from any cause, whichever occurs first.
Measured: Up to approximately 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2026
- Study startApr 2026 (estimated)
- Primary completion30 Apr 2028 (estimated)
- Study completion30 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastric AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 76 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Kechow Pharma, Inc., BeOne Medicines, RemeGen Co., Ltd.
- Responsible party
- Principal investigator, Rui-hua Xu, MD, PhD, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07507526
- Sponsor's protocol ID
- SYSUCC-HER2
- Acronym
- DTP-HER2
- Status last verified
- Mar 2026
- First submitted
- 26 Mar 2026
- Last updated
- 2 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study on the Efficacy and Safety of Disitamab Vedotin Combined With Tunlametinib and PD-1 Antibody in Third-Line and Above Treatment of Patients With HER2-Overexpressing Advanced Gastric Cancer
- ClinicalTrials.gov ID
- NCT07507526
- Acronym / sponsor ID
- DTP-HER2 / SYSUCC-HER2
- Conditions
- Gastric Adenocarcinoma
- Keywords
- HER2 overexpression, HER2-ADC, MEK, immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 76 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Collaborators
- Shanghai Kechow Pharma, Inc., BeOne Medicines, RemeGen Co., Ltd.
- Study start
- Apr 2026 (estimated)
- Primary completion
- 30 Apr 2028 (estimated)
- Study completion
- 30 Apr 2028 (estimated)
- First posted
- 2 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is an open-label, single-arm, phase II clinical trial evaluating the efficacy and safety of disitamab vedotin (RC48) in combination with tunlametinib and a PD-1 antibody (tislelizumab) in patients with HER2-overexpressing advanced gastric cancer who have failed at least two lines of prior systemic therapy.
Background HER2-overexpressing gastric cancer accounts for approximately 12-23% of advanced gastric cancer cases. Disitamab vedotin, a novel anti-HER2 antibody-drug conjugate (ADC) conjugated with the microtubule inhibitor MMAE, has demonstrated an objective response rate (ORR) of 24.8% and a median overall survival (OS) of 7.9 months in third-line treatment of HER2-overexpressing advanced gastric cancer (C008 study). However, primary and acquired resistance to ADC monotherapy remains a significant clinical challenge. Preclinical studies by the study team have shown that MAPK-ERK pathway inhibition with MEK inhibitors can upregulate HER2 expression, enhance lysosomal activity, and synergistically augment the antitumor activity of HER2-ADCs both in vitro and in vivo. The combination of a MEK inhibitor with disitamab vedotin and a PD-1 antibody has demonstrated synergistic effects in humanized mouse models.
Study Design The study consists of a safety run-in phase followed by an expansion phase. The safety run-in phase will evaluate three dose levels of tunlametinib (6 mg, 9 mg, and 12 mg orally every 12 hours) in combination with fixed doses of disitamab vedotin (2.5 mg/kg intravenously every 2 weeks) and tislelizumab (400 mg intravenously every 6 weeks) to determine the recommended dose for the expansion phase.
Following determination of the recommended dose, the expansion phase will enroll additional patients to further evaluate the efficacy and safety of the triplet combination.
Treatment Regimen
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
Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-specified discontinuation criteria are met. Tumor assessments will be performed every 6 weeks ± 3 days using enhanced CT or MRI according to irRECIST criteria.
Study Objectives
Primary Objectives: To evaluate the objective response rate (ORR) and safety profile of the combination therapy
Secondary Objectives: To evaluate progression-free survival (PFS), overall survival (OS), and quality of life
Exploratory Objectives
To analyze HER2 protein expression and immune cell infiltration in pre-/post treatment tumor tissue samples
To assess changes in serum cytokine levels before and after treatment
To characterize gut microbiota composition using 16S and metagenomic sequencing of fecal samples collected at baseline, first efficacy assessment, and disease progression.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DTP | Experimental | Drug: Tunlametinib+PD-1 mAbDisitamab 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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;
- 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;
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tunlametinib+PD-1 mAbAlso: Disitamab vedotinDisitamab 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 | DTP |
Primary outcome
Objective response rate
Time frame: Up to approximately 24 months
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.
2 secondary outcomes
Overall survival
Time frame: Up to 24 months after last patient enrollment
Progression free survival
Time frame: Up to approximately 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tunlametinib+PD-1 mAb in people with Gastric Adenocarcinoma, run by Sun Yat-sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 2 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Miaozhen Qiu, MD, PhD (8602087343351, qiumzh@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (time frame: Up to approximately 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2026.