NCT05034887

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

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 64 (estimated)
• Sponsor: National Cancer Center Hospital East · Academic / Other
• Sex: All
• Age: 20 Years
• Healthy volunteers: Not accepted

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.

Detailed description

This study is an open-label, single-arm, multicenter, phase 2 clinical trial. Eligible patients are with previously untreated gastric and gastroesophageal junction adenocarcinoma as defined by cT2-4 and/or cN+ without evidence of metastatic disease. Study treatment in this study is neoadjuvant treatment with the investigational drug, T-DXd alone, followed by surgery. T-DXd will be administered at a dose of 6.4 mg/kg (decimal) by intravenous infusion every 21 days (3 weeks) for 3 cycles as the neoadjuvant treatment followed by surgery. In the combination cohort, the efficacy and safety of neoadjuvant chemotherapy combined with T-DXd, capecitabine, and durvalumab are evaluated. 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. Monotherapy will be analyzed in the following 2 analysis sets. * Patients with HER2 overexpression (IHC3+ or IHC2+ and ISH-positive \[FISH or DISH\]) in the primary lesion or metastasis (primary analysis part) * Patients with low expression of HER2 (IHC1+ or IHC2+ and negative for ISH \[FISH or DISH\]) and HER2-ECD \> 11.6 ng/mL in the primary lesion or metastasis (exploratory part) The combination cohort will be analyzed in the following analysis sets. \- Patients with HER2 overexpression (IHC3+ or IHC2+ and ISH-positive \[FISH or DISH\]) in the primary lesion or metastasis with gastric adenocarcinoma or GEJ adenocarcinoma

Conditions

• Gastric Adenocarcinoma
• Gastroesophageal Junction Adenocarcinoma

Interventions

Type	Name	Description
DRUG	Trastuzumab Deruxtecan (T-DXd) monotherapy	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.
DRUG	T-DXd, Durvalumab and Capecitabine Combination	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.

Timeline

• Start date: 2022-01-31
• Primary completion: 2028-03-31
• Completion: 2029-03-31
• First posted: 2021-09-05
• Last updated: 2026-04-08

Locations

1 site across 1 country: Japan