HERIZON-GEA-01

• Research type

  Research Study

• Full title

  A Randomized, Multicenter, Phase 3 Study of Zanidatamab in Combination with Chemotherapy with or without Tislelizumab in Subjects with HER2-positive Unresectable Locally Advanced or Metastatic Gastroesophageal Adenocarcinoma (GEA)

• IRAS ID

  1003793

• Contact name

  Carol Schmidt

• Contact email

  carol.schmidt@zymeworks.com

• Sponsor organisation

  Zymeworks Inc.

• Eudract number

  2021-000296-36

• Research summary

  Gastroesophageal adenocarcinoma (GEA) is a rare type of cancer of the oesophagus, the tube that connects the mouth and stomach.
  Human epidermal growth factor receptor 2 (HER2) can cause cancer cells to grow and spread and HER2 is excessive within GEA patients and associated with poorer prognosis than non-HER2 GEA.

  Zanidatamab (ZW25) is a new, artificial antibody that sticks to HER2. This results in a block of pathways, growth and activation.
  Trastuzumab is also an antibody that sticks to HER2 and is approved in combination with chemotherapy.

  Tislelizumab (BGB-A317) is a new antibody that sticks to PD-1 (a protein found on immune cells) and is active when PD-L1 attaches to it and this stops a body’s immunity killing cancer cells. BGB-A317 blocks PD-1 and PD-L1 so they don’t stick, therefore the “brakes” on the immune system are released and the ability of T cells to kill cancer cells is increased.

  The objective is to compare the efficacy of ZW25 in combination with chemotherapy or in
  combination with chemotherapy and BGB A317, to trastuzumab in combination with chemotherapy in participants with GEA which is no longer treatable with surgery and/or has grown/spread to other areas.

  1,149 participants will be randomized, 1:1:1 to one of 3 groups:
  A: trastuzumab 6 mg/kg intravenously (IV) on Day 1 of each 21-day cycle, with an 8 mg/kg IV loading dose on Cycle 1, Day 1
  B: zanidatamab 1,800 mg (< 70 kg at baseline) or 2,400 mg (≥ 70 kg at baseline) IV on Day 1 of each 21-day cycle
  C: tislelizumab 200 mg IV on Day 1 of each 21-day cycle in addition to zanidatamab

  All subjects will receive chemotherapy and be on treatment until blinded independent central review confirmation of investigator-determined radiographic disease progression per RECIST 1.1.

  Study procedures include CT Scans, MUGA / Bone scans, MRI, Blood tests.

• REC name

  South Central - Berkshire B Research Ethics Committee

• REC reference

  21/SC/0247

• Date of REC Opinion

  21 Sep 2021

• REC opinion

  Further Information Favourable Opinion