A Phase 1b/2 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of Trastuzumab Deruxtecan (T-DXd) Monotherapy and Combinations in Adult Participants With HER2-expressing Gastric Cancer (DESTINY-Gastric-03)

Summary

DESTINY-Gastric03 will investigate the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary antitumor activity of trastuzumab deruxtecan (T-DXd) alone or in combination with chemotherapy and/or immunotherapy in HER2-expressing advanced/metastatic gastric/gastroesophageal junction (GEJ) and esophageal adenocarcinoma patients. Study hypotheses: Combination of T-DXd with cytotoxic chemotherapy and/or immunotherapy administered to subjects at the recommended phase 2 dose will show manageable safety and tolerability and preliminary anti-tumor efficacy so as to permit further clinical testing. T-DXd in combination with cytotoxic chemotherapy or immune checkpoint inhibitor administered to HER2-expressing gastric, GEJ and esophageal cancer patients who have not received prior treatment for advanced/metastatic disease will show preliminary evidence of anti-tumour activity and the potential to become a therapeutic option for this patient population.

Eligibility

Age range

18–130 years

Sex

All

Healthy volunteers

No

Interventions

• Drug
  Fluorouracil (5-FU)

  5-FU: administered as an IV infusion

• Drug
  Capecitabine

  Capecitabine: administered orally

• Biological
  Durvalumab

  Durvalumab: administered as an IV infusion

• Drug
  Oxaliplatin

  Oxaliplatin: administered as an IV infusion

• Biological
  Trastuzumab

  Trastuzumab: administered as an IV infusion

• Drug
  Trastuzumab deruxtecan

  T-DXd: administered as an IV infusion

• Drug
  Cisplatin

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