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Combining zanidatamab with standard treatment for advanced HER2 positive gastroesophageal cancer

A Randomized Phase II Study of Paclitaxel and Ramucirumab +/- Zanidatamab in HER2 Positive Advanced Gastroesophageal Adenocarcinoma

Phase 2 Interventional Canadian Cancer Trials Group · NCT06043427

This study is testing if adding a new drug called zanidatamab to standard treatments can help people with advanced HER2 positive gastroesophageal cancer live longer without their cancer getting worse.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment168 (estimated)
Ages18 Years and up
SexAll
SponsorCanadian Cancer Trials Group Research network
Drugs / interventionstrastuzumab, ramucirumab, chemotherapy, zanidatamab
Locations18 sites (Calgary, Alberta and 17 other locations)
Trial IDNCT06043427 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate whether adding zanidatamab to the standard treatment regimen of paclitaxel and ramucirumab can reduce the progression of HER2 positive advanced gastroesophageal adenocarcinoma. Participants will be compared based on their response to the usual treatment versus the combination treatment. The primary goal is to determine if the addition of zanidatamab can lower the risk of cancer worsening by at least 37%. The study will involve patients who have previously failed a trastuzumab-containing regimen.

Who should consider this trial

Good fit: Ideal candidates are patients with unresectable or metastatic HER2 positive gastroesophageal adenocarcinoma who have previously failed trastuzumab-based therapy.

Not a fit: Patients with HER2 negative gastroesophageal adenocarcinoma or those who have not received prior trastuzumab therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment option that significantly reduces cancer progression for patients with advanced HER2 positive gastroesophageal adenocarcinoma.

How similar studies have performed: Other studies have shown promising results with similar combinations of targeted therapies and chemotherapy in treating HER2 positive cancers.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Participants must have histologically or pathologically confirmed gastroesophageal adenocarcinoma (stomach, gastroesophageal junction or esophagus) that is unresectable or metastatic and which must be HER2 positive as confirmed by central testing using FDA-approved HER2 assay. HER2 positive is defined as IHC 3+, or IHC 2+ and FISH positive.
* Participants must have received and failed at least one prior trastuzumab-containing regimen in combination with platinum-based chemotherapy for treatment of locally advanced or metastatic disease. Failure is defined as demonstrated objective disease progression (radiologic) on the most recently administered HER2 targeting agent.
* Participants must have presence of measurable or evaluable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST 1.1).
* Participants must be considered a suitable candidate for, and able to receive chemotherapy for advanced disease with paclitaxel and ramucirumab.
* Participants must consent to the provision of samples of blood, serum and plasma in order that the specific correlative marker assays may be conducted.
* Participants must consent to provision of, and investigator(s) must confirm access to a representative formalin fixed paraffin embedded (FFPE) block of tumour tissue/ or a predetermined number of freshly cut slides of representative tumour tissue of adequate amount and quality in order that the central HER2 testing may be done
* Participants must be ≥ 18 years of age.
* Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Participants must have a life expectancy of at least 12 weeks at the time of study entry
* Imaging investigations including CT/MRI of chest/abdomen/pelvis or other scans as necessary to document all sites of disease must be done within 28 days prior to randomization
* Participants must have adequate cardiac function by ECHO or MUGA defined as EF ≥ 50%. This is to be performed within 4 weeks (preferred) but no more than 8 weeks prior to randomization
* Participants must have adequate normal organ and marrow function
* Participant is able (i.e. sufficiently fluent) and willing to complete the quality of life and/or health utility questionnaires in either English or French
* Participant consent must be appropriately obtained in accordance with applicable local and regulatory requirements.
* Participant must be accessible for treatment and follow-up. Investigators must assure themselves the participants enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
* In accordance with CCTG policy, protocol treatment is to begin within 2 working days of participant enrollment
* Participants of childbearing potential must have agreed to use a highly effective contraceptive method for the entire period of study treatment and for at least 7 months after discontinuing study therapy.

Exclusion Criteria:

* Participants with a history of other malignancies except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years. Patients with a history of other malignancies detected at an early stage and whom the investigator believes have been curatively treated and are at a low risk of recurrence MAY be eligible
* Participants receiving therapy in a concurrent clinical study. Patients must agree not to participate in other clinical studies during their participation in this trial while on study treatment
* Participants with active or uncontrolled intercurrent illness
* Participants with human immunodeficiency virus infection (positive HIV 1/2 antibodies), active hepatitis B infection (positive HBV surface antigen (HBsAg)) or positive for hepatitis C (HCV) antibody may be considered for enrollment, if infection is adequately controlled in the opinion of the investigator.
* Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy
* Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol
* Any unresolved toxicity (CTCAE grade 2 or greater) from previous anti-cancer therapy which in the opinion of the investigator puts the participant at higher than expected risk during protocol treatment. However, participants with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational products in the Investigator's opinion may be included.

Where this trial is running

Calgary, Alberta and 17 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Gastroesophageal Adenocarcinoma
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.