Ph1b/2 Study of the Safety and Efficacy of T-DXd Combinations in Advanced HER2-expressing Gastric Cancer (DESTINY-Gastric03)

Condition(s) studied

Investigational drug(s) / intervention(s)

Fluorouracil (5-FU): 5-FU: administered as an IV infusion

Capecitabine: Capecitabine: administered orally

Durvalumab: Durvalumab: administered as an IV infusion

Oxaliplatin: Oxaliplatin: administered as an IV infusion

Trastuzumab: Trastuzumab: administered as an IV infusion

Trastuzumab deruxtecan: T-DXd: administered as an IV infusion

Cisplatin: Cisplatin: administered as an IV infusion

Pembrolizumab: Pembrolizumab: administered as an IV infusion

Volrustomig: Volrustomig: administered as an IV infusion

Rilvegostomig: Rilvegostomig: administered as an IV infusion

Study 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

Primary outcome measure(s)

• Part 1: Occurrence of adverse events (AEs) and serious adverse events (SAEs), graded according to NCI CTCAE v5.0 — Safety will be assessed up to the follow-up period, approximately 24 months.
  Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0
• Part 1: Ocurrence of dose-limiting toxicities (DLTs) — Safety will be assessed up to the follow-up period, approximately 24 months.
  Occurrence of dose limiting toxicities
• Part 1: Changes from baseline in laboratory parameters — Safety will be assessed up to the follow-up period, approximately 24 months.
  Changes in laboratory parameters (every in appropriate units) compared to baseline results.
• Part 1: Changes from baseline in vital signs — Safety will be assessed up to the follow-up period, approximately 24 months.
  Changes in vital signs results compared to baseline results.
• Part 1: Changes from baseline in electrocardiogram (ECG) results — Safety will be assessed up to the follow-up period, approximately 24 months.
  Changes in ECG results compared to baseline results.
• Part 2, Part 3, Part 4 and Part 5: Endpoint assessed by Investigator per RECIST v1.1: Confirmed Objective Response Rate (ORR) — (Endpoint: ORR) Efficacy will be assessed at an average of approximately 12 months
  Confirmed ORR per RECIST 1.1 is the percentage of patients with Complete Response or Partial Response that is subsequently confirmed.

Trial sites (71)

+ 31 more sites — see the full list on the official registry below.

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