HER2-positive Gastric CancerPhase 1/2NCT06572319
Disitamab Vedotin Plus Trastuzumab in Patients With HER2 Positive GC/GEJ Patiens
A Phase 1/2 study testing Disitamab Vedotin(RC48) Plus Tratuzumab in people with HER2-positive Gastric Cancer and HER2-positive Gastroesophageal Junction Adenocarcinoma, run by Zhejiang Cancer Hospital at 1 site in China.
Trial summary
This trial is a single center, single arm, open label clinical study aimed at evaluating the efficacy and safety of the combination therapy of Disitamab Vedotin and trastuzumab in the treatment of advanced HER-2 positive gastric/gastroesophageal junction tumors Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- HER2-positive Gastric Cancer, HER2-positive Gastroesophageal Junction Adenocarcinoma
- What is being tested?
- Disitamab Vedotin(RC48) Plus Tratuzumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2024to 31 Dec 2026
- Phase
- Phase 1/2
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Sign the informed consent form; 2.18-75 years old (including 18 years old, excluding 75 years old), gender not limited; 3. The pathological histology confirmed by pathology is adenocarcinoma of the gastric/gastroesophageal junction; 4. HER2 positive tumor criteria (primary tumor or metastatic lesion, HER2 positive is defined as IHC 2+/FISH+(HER2: CEP17 ratio ≥ 2.0) or IHC (3+). Using the criteria for interpreting HER2 in gastric cancer 5. Recurrent or metastatic diseases that cannot be surgically treated, with at least one measurable lesion (RECIST 1.1 criteria) in the subject and an estimated survival time of at least 12 weeks; 6. ECOG score ranges from 0 to 1 points; 7. At least first-line systemic therapy has failed (regardless of whether it includes anti-HER2 monoclonal antibody therapy); 8. Having sufficient bone marrow, liver and kidney function:
- Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelets ≥ 90 × 109/L, or
- hemoglobin ≥ 9g/dL;
- ALT or AST levels without liver metastasis are less than 2.5 times the upper limit of the normal range; When liver metastasis occurs, ALT or AST is less than 5 times the upper limit of the normal range; Serum bilirubin is 1.5 times lower than the upper limit of the normal reference range;
- Serum creatinine is lower than 1.5 times the upper limit of the normal reference range or creatinine clearance rate is ≥ 40ml/min; 9. Women of childbearing age and their spouses are willing to use effective contraceptive methods within the last 7 months of treatment.
Who cannot join
- Known to be allergic to the received therapeutic drugs or excipients;
- Baseline LVEF<50% (measured by echocardiography or MUGA);
- Previously received treatment with anti-HER2 ADC drugs;
- Individuals who have undergone systemic immunotherapy, biologic therapy, or participated in any clinical drug trials within the past 2 weeks;
- Those who have undergone surgery within 3 weeks before the start of the experimental treatment and have not fully recovered;
- Patients with uncontrolled central nervous system (CNS) metastases or epilepsy requiring medication treatment;
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- Serious systemic diseases. Such as infected or uncontrolled diabetes;
- Suffering from other malignant tumors within 5 years, except for non melanoma skin cancer and cervical carcinoma in situ;
- Clinically symptomatic active coronary heart disease, cardiomyopathy, or congestive heart failure, NYHA III-IV; uncontrolled hypertension (systolic blood pressure>180 mmHg or diastolic blood pressure>100 mmHg), clinically symptomatic heart valve disease, or high-risk arrhythmia;
- Patients receiving long-term or high-dose corticosteroid treatment (inhaled steroids or short-term oral steroids are allowed to resist vomiting or promote appetite)
- Individuals without legal capacity, those whose medical or ethical reasons affect the continuation of research;
- Pregnant and lactating female patients, or those who wish to become pregnant during treatment;
- Uncontrolled pleural and peritoneal effusion;
- There is a persistent infection of>level 2 (CTC-AE 4.0); Wounds, ulcers, or fractures that cannot heal, or patients with a history of organ transplantation;
- There are unresolved toxicity levels>1 caused by any previous treatment/procedure (CTC-AE 4.0, excluding hair loss, anemia, and hypothyroidism);
- After comprehensive assessment of the patient's condition by the researchers, it is deemed that they are not suitable to participate in this study;
- Simultaneously participating in another clinical study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Jieer Ying, M.D. contact
China1 site, 1 recruiting
- Recruiting
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310022
Jieer Ying, Doctor, 13858195803, hzyingjieer@163.com
About this study
Official title: Phase I/II Clinical Study of the Combination of Disitamab Vedotin and Trastuzumab in the Treatment of HER2 Positive Gastric/Gastroesophageal Junction Tumors With Previous Systemic Therapy Failure
This trial is a single center, single arm, open label clinical study aimed at evaluating the efficacy and safety of the combination therapy of Disitamab Vedotin and trastuzumab in the treatment of advanced HER-2 positive gastric/gastroesophageal junction tumors
Read the detailed description
In a specific tumor area, the absorption of antibodies is driven by its blood vessels or permeable surface, while the microscopic distribution depends on the number of binding sites available for the specific antibody. Due to the much faster binding rate of antibodies to their targets than their diffusion rate, their penetration into tumor tissue is severely limited (such as binding site barriers). This will limit the drug's penetration into the tumor before the antibody reaches saturation dose. Due to the toxicity brought by the toxins carried by ADC itself (toxin shedding, non-specific endocytosis, or on target, off tumor toxicity), its dose will be relatively reduced compared to naked antibodies. By adding naked antibodies or directly reducing DAR, the dose of ADC can be increased to overcome the binding site barrier and improve the tumor penetration of antibody drugs. In theory, if the antibody dose is large enough, the antibody will reach all (accessible) binding points within the tumor and saturate both the interior and periphery of the tumor.
In addition, in addition to ADC drugs, chemotherapy, immunotherapy, targeted therapy, and other options are also available for HER2 positive gastric cancer posterior line, but the efficacy is still unclear. Therefore, it is urgent to explore new treatment options to further improve the efficacy of this special population.
Therefore, we designed this Phase I/II clinical trial to explore whether the combination of RC48 and naked anti trastuzumab currently on the market can improve efficacy.
- Being tested
- Disitamab Vedotin(RC48) Plus Tratuzumab
- Keywords
- HER-2, ADC, Disitamab Vedotin, trastuzumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Disitamab Vedotin(RC48) Plus TratuzumabDrug
Disitamab Vedotin: 2.5mg/kg，ivgtt，D1, every 2 weeks for a treatment cycle. Tratuzumab: RP2D，ivgtt，D1, every 2 weeks for a treatment cycle.
| Study group | Role | What they receive |
|---|---|---|
| Phase Ⅰ/Ⅱ： Disitamab Vedotin(RC48) Plus Tratuzumab | Experimental | Dose exploration： Disitamab Vedotin（RC48）: 2.5mg/kg，ivgtt，D1, every 2 weeks for a treatment cycle.
Tratuzumab:"3+3"Design，1mg/kg Q2W，2.5mg/kg Q2W，4mg/kg Q2W Dose expansion： Disitamab Vedotin（RC48）: 2.5mg/kg，ivgtt，D1, every 2 weeks for a treatment cycle.
Tratuzumab: RP2D Receives: Drug: Disitamab Vedotin(RC48) Plus Tratuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate(ORR)
he number of cases in which tumor size is reduced to PR or CR / the total number of evaluable cases (%)
Measured: 12 months
Secondary outcomes (4)
Overall survival (OS)
The time interval between the start date of study drug and the date of death (any cause)
Measured: up to 36 months
Progression-free survival (PFS)
Refers to the date from the date of admission to the date of the first progression of disease or death of any cause, using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
Measured: up to 12 months
Disease control rate (DCR)
Percentage of confirmed cases including complete remission (CR), partial remission (PR) and disease stability (SD) among patients with evaluable efficacy
Measured: up to 12 months
Incidence of Treatment-Emergent 3/4 Adverse Events
Number and percentage of participants with Adverse Events (any Grade and Grade 3/4)
Measured: up to 12 months after enrollment or study close
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2024
- Study start1 Sep 2024 (estimated)
- Primary completion1 Aug 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2-positive Gastric CancerStudies of the same condition, open and under way.
- More trials run by Zhejiang Cancer HospitalThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhejiang Cancer Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ying Jieer, Zhejiang Cancer Hospital
- Investigators
- Jieer Ying, M.D., Principal investigator, Zhejiang Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06572319
- Sponsor's protocol ID
- IRB-2024-278
- Status last verified
- Aug 2024
- First submitted
- 23 Aug 2024
- Last updated
- 27 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Clinical Study of the Combination of Disitamab Vedotin and Trastuzumab in the Treatment of HER2 Positive Gastric/Gastroesophageal Junction Tumors With Previous Systemic Therapy Failure
- ClinicalTrials.gov ID
- NCT06572319
- Acronym / sponsor ID
- IRB-2024-278
- Keywords
- HER-2, ADC, Disitamab Vedotin, trastuzumab
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Zhejiang Cancer HospitalUniversity, hospital or other
- Study start
- 1 Sep 2024 (estimated)
- Primary completion
- 1 Aug 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 27 Aug 2024 (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.
This trial is a single center, single arm, open label clinical study aimed at evaluating the efficacy and safety of the combination therapy of Disitamab Vedotin and trastuzumab in the treatment of advanced HER-2 positive gastric/gastroesophageal junction tumors
Detailed description
In a specific tumor area, the absorption of antibodies is driven by its blood vessels or permeable surface, while the microscopic distribution depends on the number of binding sites available for the specific antibody. Due to the much faster binding rate of antibodies to their targets than their diffusion rate, their penetration into tumor tissue is severely limited (such as binding site barriers). This will limit the drug's penetration into the tumor before the antibody reaches saturation dose. Due to the toxicity brought by the toxins carried by ADC itself (toxin shedding, non-specific endocytosis, or on target, off tumor toxicity), its dose will be relatively reduced compared to naked antibodies. By adding naked antibodies or directly reducing DAR, the dose of ADC can be increased to overcome the binding site barrier and improve the tumor penetration of antibody drugs. In theory, if the antibody dose is large enough, the antibody will reach all (accessible) binding points within the tumor and saturate both the interior and periphery of the tumor.
In addition, in addition to ADC drugs, chemotherapy, immunotherapy, targeted therapy, and other options are also available for HER2 positive gastric cancer posterior line, but the efficacy is still unclear. Therefore, it is urgent to explore new treatment options to further improve the efficacy of this special population.
Therefore, we designed this Phase I/II clinical trial to explore whether the combination of RC48 and naked anti trastuzumab currently on the market can improve efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phase Ⅰ/Ⅱ： Disitamab Vedotin(RC48) Plus Tratuzumab | Experimental | Drug: Disitamab Vedotin(RC48) Plus TratuzumabDose exploration： Disitamab Vedotin（RC48）: 2.5mg/kg，ivgtt，D1, every 2 weeks for a treatment cycle. Tratuzumab:"3+3"Design，1mg/kg Q2W，2.5mg/kg Q2W，4mg/kg Q2W Dose expansion： Disitamab Vedotin（RC48）: 2.5mg/kg，ivgtt，D1, every 2 weeks for a treatment cycle. Tratuzumab: RP2D |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 1. Sign the informed consent form; 2.18-75 years old (including 18 years old, excluding 75 years old), gender not limited; 3. The pathological histology confirmed by pathology is adenocarcinoma of the gastric/gastroesophageal junction; 4. HER2 positive tumor criteria (primary tumor or metastatic lesion, HER2 positive is defined as IHC 2+/FISH+(HER2: CEP17 ratio ≥ 2.0) or IHC (3+). Using the criteria for interpreting HER2 in gastric cancer 5. Recurrent or metastatic diseases that cannot be surgically treated, with at least one measurable lesion (RECIST 1.1 criteria) in the subject and an estimated survival time of at least 12 weeks; 6. ECOG score ranges from 0 to 1 points; 7. At least first-line systemic therapy has failed (regardless of whether it includes anti-HER2 monoclonal antibody therapy); 8. Having sufficient bone marrow, liver and kidney function:
- Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelets ≥ 90 × 109/L, or
- hemoglobin ≥ 9g/dL;
- ALT or AST levels without liver metastasis are less than 2.5 times the upper limit of the normal range; When liver metastasis occurs, ALT or AST is less than 5 times the upper limit of the normal range; Serum bilirubin is 1.5 times lower than the upper limit of the normal reference range;
- Serum creatinine is lower than 1.5 times the upper limit of the normal reference range or creatinine clearance rate is ≥ 40ml/min; 9. Women of childbearing age and their spouses are willing to use effective contraceptive methods within the last 7 months of treatment.
Key exclusion criteria (17 listed)
- Known to be allergic to the received therapeutic drugs or excipients;
- Baseline LVEF<50% (measured by echocardiography or MUGA);
- Previously received treatment with anti-HER2 ADC drugs;
- Individuals who have undergone systemic immunotherapy, biologic therapy, or participated in any clinical drug trials within the past 2 weeks;
- Those who have undergone surgery within 3 weeks before the start of the experimental treatment and have not fully recovered;
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 |
|---|---|---|
| Disitamab Vedotin(RC48) Plus TratuzumabDisitamab Vedotin: 2.5mg/kg，ivgtt，D1, every 2 weeks for a treatment cycle. Tratuzumab: RP2D，ivgtt，D1, every 2 weeks for a treatment cycle. | Drug | Phase Ⅰ/Ⅱ： Disitamab Vedotin(RC48) Plus Tratuzumab |
Primary outcome
Objective response rate(ORR)
Time frame: 12 months
he number of cases in which tumor size is reduced to PR or CR / the total number of evaluable cases (%)
4 secondary outcomes
Overall survival (OS)
Time frame: up to 36 months
Progression-free survival (PFS)
Time frame: up to 12 months
Disease control rate (DCR)
Time frame: up to 12 months
Incidence of Treatment-Emergent 3/4 Adverse Events
Time frame: up to 12 months after enrollment or study close
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 27 Aug 2024.
- Individual participant dataSharing planned: No
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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.
Jieer Ying, M.D. contact
Jieer Ying, M.D. principal investigator
Zhejiang Cancer Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Disitamab Vedotin(RC48) Plus Tratuzumab in people with HER2-positive Gastric Cancer and HER2-positive Gastroesophageal Junction Adenocarcinoma, run by Zhejiang Cancer Hospital 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 5 inclusion and 17 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: looking for participants now, as of the sponsor's last update on 27 Aug 2024. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Jieer Ying, M.D. (13858195803, jieerying@aliyun.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate(ORR) (time frame: 12 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 27 Aug 2024.