Phase 2 Study of Trastuzumab Deruxtecan in the Neoadjuvant Treatment, or Trastuzumab Deruxtecan Plus Capecitabine Plus Durvalumab(MEDI4736) in the Preoperative and Postoperative Adjuvant Treatment for Patients With HER2 Positive Gastric and Gastroesophageal Junction Adenocarcinoma

NCT05034887 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: EPOC2003
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an open-label, single-arm, multicenter, Phase 2 study to evaluate the efficacy and safety of neoadjuvant chemotherapy with T-DXd monotherapy in patients with HER2-positive gastric cancer. In the combination cohort, the efficacy and safety of neoadjuvant chemotherapy combined with T-DXd, capecitabine, and durvalumab are evaluated.

Conditions

Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma

Keywords

Trastuzumab Deruxtecan T-DXd DS-8201a Gastric cancer

Outcome Measures

Primary Outcomes (1)

• Major pathological response [MPR] rate: by central assessment

  MPR is defined as the proportion of subjects with \< 10% residual tumor in the stomach and lymph nodes by central assessment

  6 months

Secondary Outcomes (8)

• MPR rate determined by the local assessment

  6 months

• Pathological complete response (pCR) rate

  6 months

• Curative Resection Rate

  6 months

• AE rate

  From the start day of study treatment, "47 days after the last dose, 30 days after surgery, or if postoperative adjuvant chemotherapy or treatment is started before it, whichever comes first.

• Percentage of completed treatment before surgery (Combination cohort only)

  3 years

Other Outcomes (5)

• Biomarkers in the Primary cohort and the Exploration cohort

  6 months

• MPR rate determined by investigator assessment in the Exploration cohort

  6 months

• pCR rate determined by investigator assessment in the Exploration cohort

  6 months

Study Arms (2)

Trastuzumab Deruxtecan (T-DXd) monotherapy

EXPERIMENTAL

One cycle is 21 days, with T-DXd repeated 3 cycles before surgery as the neo adjuvant treatment.

Drug: Trastuzumab Deruxtecan (T-DXd) monotherapy

Combination cohort

EXPERIMENTAL

T-DXd 5.4 mg/kg and Durvalumab 1500 mg were infused intravenously once 3 weeks, and Capecitabine 750 mg/m2 was administered orally twice daily for 14 days with a 7-day rest period. T-DXd, Capecitabine, and Durvalumab were repeated 3 cycles preoperatively and 3 cycles postoperatively, followed by 10 cycles of Durvalumab monotherapy every 4 weeks.

Drug: T-DXd, Durvalumab and Capecitabine Combination

Interventions

Trastuzumab Deruxtecan (T-DXd) monotherapy DRUG

T-DXd will be administered at a dose of 6.4 mg/kg (decimal) by intravenous infusion every 21 days (3 weeks) for subsequent three cycles.

Also known as: DS-8201a

Trastuzumab Deruxtecan (T-DXd) monotherapy

T-DXd, Durvalumab and Capecitabine Combination DRUG

Administer each cycle over 21 days. T-DXd is administered by intravenous infusion at 5.4 mg/kg every 21 days (every 3 weeks). Capecitabine is given at 750 mg/m2 BID, taken orally for 14 days, followed by a drug holiday from the evening of Day 15 to the morning of Day 22 (Day 1 of the next cycle). Durvalumab is administered at 1500 mg by intravenous infusion over 60 minutes every 21 days (every 3 weeks). As neoadjuvant chemotherapy, administer T-DXd, Capecitabine, and Durvalumab in combination on a q3w schedule for 3 cycles. As adjuvant chemotherapy consists of T-DXd, Capecitabine, and Durvalumab in combination on a q3w schedule for 3 cycles, followed by Durvalumab monotherapy on a q4w schedule until 10 cycles are completed.

Combination cohort

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed adenocarcinoma of the gastric or gastroesophageal junction.
• Has HER2 overexpression (IHC3+, or IHC2+ and ISH positive \[FISH or DISH\]). (HER2 Low expression: IHC1+, or IHC2+ and ISH-negative \[FISH or DISH\] with HER2-ECD \> 11.6 ng/mL in the exploratory cohort).
• Have previously untreated gastric and gastroesophageal junction adenocarcinoma and cT2-4 and/or cN+M0.according to the UICC TNM classification (8th edition),
• Age ≥ 20 years as the day of informed consent.
• Has an ECOG performance status (PS) of 0 or 1.
• Has a left ventricular ejection fraction (LVEF) ≥ 50% by either echocardiogram (ECHO) or multigated collecting acquisition (MUGA) scan within 28 days before enrollment (acceptable on the same day of the week).
• Has a corrected QT interval (QTc) ≦ 470 ms in females, or QTc ≦ 450 ms in males based on a 12-lead ECG screening within 28 days before enrollment (allowed on the same day of the week). \[Fridericia's correction is recommended\]
• Satisfies all of the following requirements within 14 days before enrollment (allowed on the same day of the week).
• Absolute neutrophil count ≧1500 / mm3 \[except for assessment ≦ 14 days after administration of Granules colony-stimulating factors (G-CSF)\]
• Hemoglobin ≧ 8.0 g/dL (except for those measured within 7 days after whole blood transfusion or packed red blood cells)
• Platelet count ≧100000 per mm3 (excluding measurements within 7 days after platelet transfusion).
• Total bilirubin ≦1.5 mg/dL (patients with gilbert's syndrome will be allowed if they have \< 3.0 mg/dL).
• AST(GOT)≦100 IU/L
• ALT(GPT)≦100 IU/L
• Serum albumin ≧ 2.5 g/dL

You may not qualify if:

• Has a medical history of myocardial infarction or congestive heart failure (New York Heart Association Classes II-IV) within 6 months before enrollment, corresponding to the value diagnosed as myocardial infarction as defined by the \*validated test within 28 days before enrollment (allowed on the same day), unstable angina, or any serious arrhythmia requiring treatment.
• tested in local institutions \*\*: Enrollment is allowed with value exceeds ULN if myocardial infarction can be excluded.
• Active other cancers \[Synchronous other cancers and metachronous other cancers within 3 years prior to enrollment, but carcinoma in situ or other lesions corresponding to mucosal carcinoma that are considered curable with local treatment will not be included in active other cancers.\]
• Has serious (hospitalized) complications (intestinal palsy, intestinal obstruction, pulmonary fibrosis, diabetes mellitus that is difficult to control, heart failure, myocardial infarction, unstable angina, renal failure, liver failure, psychiatric disorders, cerebrovascular disorders, etc.).
• Has history of gastrointestinal perforation and/or gastrointestinal fistula within 6 months before enrollment.
• Has any of the following infections:
• HBs antigen positive
• HBs antibody or HBc antibody and HBV-DNA positive
• Active hepatitis C (eg, if HCV RNA is detected qualitatively) Patients who are HBsAg positive but who have achieved HBV DNA level \< 1.3 log IU/mL (2.1 log copies/mL) after treatment with antiviral drugs such as NAs, are eligible for the study.
• HIV infection
• Lung diseases defined as:
• Has a history of non-infectious interstitial lung disease or pneumonitis that required treatment, has interstitial lung disease or pneumonitis, or these lung diseases cannot be ruled out by radiographic examination before enrollment.
• Severe pulmonary disease (eg, pulmonary embolism within 3 months prior to enrollment, serious bronchial asthma, severe COPD, restrictive pulmonary disease, or pleural effusion).
• Lung-related autoimmune or connective tissue or inflammatory diseases (eg, rheumatoid arthritis, Sjögren's syndrome, or sarcoidosis) with clinically severe pulmonary risks.
• Has history of pneumonectomy.

Sponsors & Collaborators

• National Cancer Center Hospital East: lead
• Daiichi Sankyo Co., Ltd.: collaborator

Study Sites (1)

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

Location

MeSH Terms

Interventions

trastuzumab deruxtecan; durvalumab

Study Officials

• Kohei Shitara, MD

  National Cancer Center Hospital East

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Gastroenterology and Gastrointestinal Oncology Division

Study Record Dates

• First Submitted: September 2, 2021
• First Posted: September 5, 2021
• Study Start: January 31, 2022
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)