Gastric CancerPhase 1/2NCT05894824
T-Dxd in Combination With Ramucirumab as HER2 Low Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
A Phase 1/2 study testing T-Dxd(Trastuzmab deruxtecan), Ramucirumab in people with Gastric Cancer and Gastroesophageal Junction (GEJ) Cancer, run by Yonsei University at 1 site in South Korea.
Trial summary
This is a Phase Ib/II study to identify the RP2D of T-DXd combination with Ram and to assess the safety and clinical efficacy of this combined treatment in advanced gastric cancer. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Gastric Cancer, Gastroesophageal Junction (GEJ) Cancer
- What is being tested?
- T-Dxd(Trastuzmab deruxtecan), Ramucirumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteSouth Korea
- Study dates
- 5 Feb 2024to 1 Jan 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able and willing to give written informed consent and has signed the appropriate weitten informed consent form(ICF) prior to performance of any trial activityes.
- Eligible male and female subjects aged ≥19 years.
- Histologically or cytologically proven metastatic or locally advanced HER2 low gastric or GEJ adenocarcinoma: The definition of HER2 low is 1+ by immunohistochemistry (IHC) or 2+ by IHC and without HER2 gene amplification (negative by in situ hybridization[ISH]).
- Progressed after 1st line palliative treatment. Adjuvant chemotherapy will be counted as 1st line treatment if the cancer has recurred within 6 months of completion of adjuvant chemotherapy.
- Has measurable or evaluable disease as determined by RECIST ver 1.1.
- ECOG performance status of 0 -1 at trial entry.
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- Life expectancy ≥12 weeks as judged by the Investigator.
- Has LVEF ≥ 50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before enrollment.
- Adequate baseline organ function defined as:
- Absolute neutrophil count ≥1500/mm3
- Platelets ≥100,000/mm3
- Hemoglobin ≥9.0 g/dL
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 × upper limit of normal (ULN) of the study site (or ≤5.0 × ULN in patients with liver metastases)
- Total bilirubin ≤1.5 × ULN - Serum albumin ≥2.5 g/dL
- Creatinine ≤1.5 × ULN or creatinine clearance (either measured value or estimated value using the Cockcroft-Gault equation) >40ml/min - Urinary protein ≤1+ on dipsick or routine urinalysis - INR and PTT/aPTT ≤1.5 × ULN 10. Adequate treatment washout period before randomization/enrollment. - Major Surgery ≥ 4 weeks - Radiation Therapy including palliative stereotactic radiation therapy to chest ≥ 4 weeks
- Anti-Cancer chemotherapy [Immunotherapy (non-antibody based therapy)] ≥ 3 weeks
- 11. Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential who are sexually active with a non-sterilized male partner.
- 12. Female patients of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception from the time of screening and must agree to continue using such precautions for 7 months after the last dose of IMP.
- 13. Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to 4 months after the final dose of IMP. 14. Female subjects must not donate, or retrieve for their own use, ova from the time of enrollment and throughout the study treatment period, and for at least 7 months after the final study drug administration
Who cannot join
- Anticancer treatment within 14 days before the start of trial treatment.
- Major surgery within 28 days before the start of trial treatment.
- Have received more than 2 prior lines of chemotherapy.
- Grade ≥ 2 peripheral neuropathy.
- Multiple primary malignancies within 3 years.
- Participants with a medical history of myocardial infarction within 6 months before treatment, symptomatic CHF (New York Heart Association Class II to IV), unstable angina pectoris, clinically important cardiac arrhythmias, or a recent (< 6 months) cardiovascular event, including myocardial infarction, unstable angina pectoris, and stroke.
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- Corrected QT interval (QTcF) prolongation to > 470 msec (females) or >450 msec (males) based on an average of the screening triplicate 12-lead ECG.
- Gastrointestinal perforation or fistula or any Grade 3-4 bleeding within 3 months of first dose of protocol therapy; or any arterial thromboembolic event, significant gastro-intestinal bleeding or any significant venous thromboembolism within 3 months before treatment
- History of (non-infectious) ILD / pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- Lung criteria: A. Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder. B. Any autoimmune, connective tissue or inflammatory disorders C. Prior pneumonectomy
- Has known active CNS metastases and/or carcinomatous meningitis.
- Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions that may, in the opinion of the investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results.
- Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
- Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
- Active primary immunodeficiency, known uncontrolled active HIV infection or active hepatitis B or C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1 Day 1. 16. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. 17. Receipt of live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of trastuzumab deruxtecan. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IMP. 18. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤ 1 or baseline. 19. Known allergy or hypersensitivity to study treatment or any of the study drug excipients.
- 20. History of severe hypersensitivity reactions to other monoclonal antibodies.
- 21. Pregnant or breastfeeding female patients, or patients who are planning to become pregnant.
- 22. Otherwise inappropriate for this study in the investigator's or sub-investigator's opinion.
- 23. Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis.
- 24. Serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy.
- 25. The patient is receiving chronic antiplatelet therapy, including dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted.
- 26. The patient has uncontrolled or poorly-controlled hypertension (>160 mmHg systolic or > 100 mmHg diastolic for >4 weeks) despite standard medical management.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
South Korea1 site, 1 recruiting
- Recruiting
Sun Young Rha
Seoul, Seoul, 03722
About this study
Official title: An Open Label, Single-arm, Multicenter Phase Ib/II Study to Evaluate the Safety and Efficacy of T-Dxd in Combination With Ramucirumab as a 2nd Line in Patients With HER2 Low Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
This is a Phase Ib/II study to identify the RP2D of T-DXd combination with Ram and to assess the safety and clinical efficacy of this combined treatment in advanced gastric cancer. The study will be conducted in two parts: Phase Ib dose escalation study to determine the MTD and RP2D of T-DXd combination and Ram, and Phase II to further evaluate the safety and tolerability of T-DXd combinations with Ram at the RP2D and determine anti-tumor activity.
Read the detailed description
This is a Phase Ib/II study to identify the RP2D of T-DXd combination with Ram and to assess the safety and clinical efficacy of this combined treatment in advanced gastric cancer after first-line treatment. The study will be conducted in two parts: Phase Ib dose escalation study to determine the MTD and RP2D of T-DXd combination and Ram, and Phase II to further evaluate the safety and tolerability of T-DXd combinations with Ram at the RP2D and determine anti-tumor activity.
- Being tested
- T-Dxd(Trastuzmab deruxtecan), Ramucirumab
- Keywords
- HER2 gastric cancer, T-Dxd, Ramucirumab
- Medical subject headings
- Stomach Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
T-Dxd(Trastuzmab deruxtecan), RamucirumabDrug
Also called Enhertu, Cyramza
Phase Ib will use a standard 3+3 scheme with the planned doses of T-DXd (4.4~6.4 mg/kg) once every 3 weeks in combination with Ramucirumab 8mg/kg administered once every 2 weeks.
- Dosing Regimen
- Trastruzumab deruxtecan : One IV infusion every 3 weeks on Day 1 of each 21-day cycle
- Ramucirumab : One IV infusion on every 2 weeks on Day 1,15 of each 28-day cycle
| Study group | Role | What they receive |
|---|---|---|
| Single arm, Trastruzumab deruxtecan, Ramucirumab | Other | Single arm, Trastruzumab deruxtecan, Ramucirumab Receives: Drug: T-Dxd(Trastuzmab deruxtecan), Ramucirumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
RP2D
Maximum Tolerated dose (MTD) and Recommended phase 2 dose as determined by Dose limiting Toxicity (DLT).
Measured: within first 6 weeks of treatment
PFS rate at 24 weeks
Defined as the time from start of study treatment until the date of objective disease progression or death (by any cause in the absence of disease progression) Progression is defined in accordance with the RECIST v1.1 criteria. Determination of PFS rate at 24 weeks.
Measured: within first 2 4weeks of treatment
Secondary outcomes (6)
Overall Survival (OS)
Defined from the date of treatment assignment until the date of death due to any cause. Any participant not known to have died at the time of analysis will be censored based on the last recorded date on which the participant was known to be alive.
Measured: 6 months after the last treatment of the last subject
Objective Response Rate (ORR)
Defined as the proportion of participants with measurable disease who achieve complete response(CR) or partial response(PR), as determined by the Investigator per RECIST v1.1. Data obtained up until disease progression, or the last evaluable assessment in the absence of progression, will be included in the assessment of ORR. Confirmatory scan is needed for the patients with CR or PR after 4 weeks of the first response. Participants who discontinue treatment without progression, receive a subsequent therapy, and then respond, will not be included as responders in the ORR.
Measured: 6 months after the last treatment of the last subject
Disease Control Rate (DCR)
Defined as the percentage of participants who have a confirmed CR or PR or who have SD (without subsequent cancer therapy) after the date of treatment assignment.
Measured: 6 months after the last treatment of the last subject
Duration of Response (DoR)
Defined as the percentage of participants who have a confirmed CR or PR or who have SD (without subsequent cancer therapy) after the date of treatment assignment.
Measured: 6 months after the last treatment of the last subject
Progression-free survival (PFS)
Defined as time from the date of treatment assignment until progression per RECIST v1.1 as assessed by the Investigator, or death due to any cause. Participants who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable RECIST v1.1 assessment.
Measured: 6 months after the last treatment of the last subject
adverse events categorized in accordance with CTCAE 5.0 Criteria.
Safety and tolerability
Measured: 6 months after the last treatment of the last subject
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2023
- Study start5 Feb 2024
- Primary completion1 Dec 2025 (estimated)
- Study completion1 Jan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastric CancerStudies of the same condition, open and under way.
- More trials run by Yonsei 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 58 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sun Young Rha, Yonsei University
- Investigators
- SUN YOUNG RHA, Principal investigator, Yonsei Cancer Center, Yonsei University College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05894824
- Sponsor's protocol ID
- 4-2023-0392
- Status last verified
- Jul 2025
- First submitted
- 31 May 2023
- Last updated
- 11 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- 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 11 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Single-arm, Multicenter Phase Ib/II Study to Evaluate the Safety and Efficacy of T-Dxd in Combination With Ramucirumab as a 2nd Line in Patients With HER2 Low Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
- ClinicalTrials.gov ID
- NCT05894824
- Acronym / sponsor ID
- 4-2023-0392
- Keywords
- HER2 gastric cancer, T-Dxd, Ramucirumab
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 58 participants (estimated)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- 5 Feb 2024 (actual)
- Primary completion
- 1 Dec 2025 (estimated)
- Study completion
- 1 Jan 2026 (estimated)
- First posted
- 8 Jun 2023 (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 is a Phase Ib/II study to identify the RP2D of T-DXd combination with Ram and to assess the safety and clinical efficacy of this combined treatment in advanced gastric cancer. The study will be conducted in two parts: Phase Ib dose escalation study to determine the MTD and RP2D of T-DXd combination and Ram, and Phase II to further evaluate the safety and tolerability of T-DXd combinations with Ram at the RP2D and determine anti-tumor activity.
Detailed description
This is a Phase Ib/II study to identify the RP2D of T-DXd combination with Ram and to assess the safety and clinical efficacy of this combined treatment in advanced gastric cancer after first-line treatment. The study will be conducted in two parts: Phase Ib dose escalation study to determine the MTD and RP2D of T-DXd combination and Ram, and Phase II to further evaluate the safety and tolerability of T-DXd combinations with Ram at the RP2D and determine anti-tumor activity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm, Trastruzumab deruxtecan, Ramucirumab | Other | Drug: T-Dxd(Trastuzmab deruxtecan), RamucirumabSingle arm, Trastruzumab deruxtecan, Ramucirumab |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Able and willing to give written informed consent and has signed the appropriate weitten informed consent form(ICF) prior to performance of any trial activityes.
- Eligible male and female subjects aged ≥19 years.
- Histologically or cytologically proven metastatic or locally advanced HER2 low gastric or GEJ adenocarcinoma: The definition of HER2 low is 1+ by immunohistochemistry (IHC) or 2+ by IHC and without HER2 gene amplification (negative by in situ hybridization[ISH]).
- Progressed after 1st line palliative treatment. Adjuvant chemotherapy will be counted as 1st line treatment if the cancer has recurred within 6 months of completion of adjuvant chemotherapy.
- Has measurable or evaluable disease as determined by RECIST ver 1.1.
Key exclusion criteria (22 listed)
- Anticancer treatment within 14 days before the start of trial treatment.
- Major surgery within 28 days before the start of trial treatment.
- Have received more than 2 prior lines of chemotherapy.
- Grade ≥ 2 peripheral neuropathy.
- Multiple primary malignancies within 3 years.
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 |
|---|---|---|
| T-Dxd(Trastuzmab deruxtecan), RamucirumabAlso: Enhertu, CyramzaPhase Ib will use a standard 3+3 scheme with the planned doses of T-DXd (4.4~6.4 mg/kg) once every 3 weeks in combination with Ramucirumab 8mg/kg administered once every 2 weeks. * Dosing Regimen * Trastruzumab deruxtecan : One IV infusion every 3 weeks on Day 1 of each 21-day cycle * Ramucirumab : One IV infusion on every 2 weeks on Day 1,15 of each 28-day cycle | Drug | Single arm, Trastruzumab deruxtecan, Ramucirumab |
Primary outcome
RP2D
Time frame: within first 6 weeks of treatment
Maximum Tolerated dose (MTD) and Recommended phase 2 dose as determined by Dose limiting Toxicity (DLT).
PFS rate at 24 weeks
Time frame: within first 2 4weeks of treatment
Defined as the time from start of study treatment until the date of objective disease progression or death (by any cause in the absence of disease progression) Progression is defined in accordance with the RECIST v1.1 criteria. Determination of PFS rate at 24 weeks.
6 secondary outcomes
Overall Survival (OS)
Time frame: 6 months after the last treatment of the last subject
Objective Response Rate (ORR)
Time frame: 6 months after the last treatment of the last subject
Disease Control Rate (DCR)
Time frame: 6 months after the last treatment of the last subject
Duration of Response (DoR)
Time frame: 6 months after the last treatment of the last subject
Progression-free survival (PFS)
Time frame: 6 months after the last treatment of the last subject
adverse events categorized in accordance with CTCAE 5.0 Criteria.
Time frame: 6 months after the last treatment of the last subject
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 11 Jul 2025.
- 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.
SUN YOUNG RHA principal investigator
Yonsei Cancer Center, Yonsei University College of Medicine
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 T-Dxd(Trastuzmab deruxtecan), Ramucirumab in people with Gastric Cancer and Gastroesophageal Junction (GEJ) Cancer, run by Yonsei University at 1 site in South Korea.
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 19 inclusion and 22 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 11 Jul 2025. 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 South Korea. 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 SUN YOUNG RHA (82-2-2228-8053, rha7655@yuhs.ac), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
RP2D (time frame: within first 6 weeks of treatment). The study lists 2 primary outcomes in all. 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 11 Jul 2025.