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Combination treatment for HER2 positive metastatic colorectal cancer

An Open-label Randomized Phase 3 Study of Tucatinib in Combination With Trastuzumab and mFOLFOX6 Versus mFOLFOX6 Given With or Without Either Cetuximab or Bevacizumab as First-line Treatment for Subjects With HER2+ Metastatic Colorectal Cancer

Phase 3 Interventional Seagen Inc. · NCT05253651

This study is testing a new combination of tucatinib, trastuzumab, and mFOLFOX6 to see if it helps people with HER2 positive metastatic colorectal cancer more than the usual treatments.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment400 (estimated)
Ages18 Years and up
SexAll
SponsorSeagen Inc. Industry-sponsored
Drugs / interventionschemotherapy, radiation, trastuzumab, bevacizumab, cetuximab, tucatinib
Locations382 sites (Glendale, Arizona and 381 other locations)
Trial IDNCT05253651 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of tucatinib combined with trastuzumab and mFOLFOX6 compared to standard care treatments for patients with HER2 positive metastatic colorectal cancer. Participants will be randomly assigned to receive either the combination therapy or standard treatments, which may include mFOLFOX6 alone or with other agents like bevacizumab or cetuximab. The study aims to assess both the efficacy of the new treatment regimen and the side effects experienced by participants.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed HER2 positive metastatic or unresectable colorectal cancer.

Not a fit: Patients with HER2 negative colorectal cancer or those who have previously received treatment for their metastatic disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective option for patients with HER2 positive metastatic colorectal cancer.

How similar studies have performed: Other studies have shown promising results with similar combination therapies in HER2 positive cancers, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Histologically and/or cytologically confirmed adenocarcinoma of the colon or rectum which is locally advanced unresectable or metastatic
* Able to provide the most recently available formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks (or freshly sectioned slides) obtained prior to treatment initiation to a central laboratory

  * If archival tissue is not available, a newly-obtained baseline biopsy of an accessible tumor lesion is required within 35 days prior to start of study treatment
* HER2+ disease as determined by a tissue based assay performed at a central laboratory.
* Participant has rat sarcoma viral oncogene homolog wild-type (RAS WT) disease as determined by local or central testing. For central RAS analysis, tissue sample must be analyzed within 1 year of biopsy date.
* Radiographically measurable disease per RECIST v1.1 with:

  * At least one site of disease that is measurable and that has not been previously irradiated, or
  * If the participant has had previous radiation to the target lesion(s), there must be evidence of progression since the radiation
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* CNS Inclusion - based on contrast brain magnetic resonance imaging, participants may have any of the following:

  * No evidence of brain metastases
  * Previously treated brain metastases which are asymptomatic

Exclusion Criteria:

* Prior systemic anticancer therapy for colorectal cancer (CRC) in the locally advanced unresectable or metastatic setting; note that participants may have received a maximum of 2 doses of mFOLFOX6 in the locally advanced/unresectable or metastatic setting prior to randomization.

  * Note: May have received chemotherapy for CRC in the adjuvant setting if it was completed \>6 months prior to enrollment
* Radiation therapy within 14 days prior to enrollment (or within 7 days in the setting of stereotactic radiosurgery)
* Previous treatment with anti-HER2 therapy
* Ongoing Grade 3 or higher neuropathy
* Active or untreated gastrointestinal (GI) perforation at the time of screening.

Where this trial is running

Glendale, Arizona and 381 other locations

+332 more sites — see ClinicalTrials.gov for the full list.

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 Colorectal NeoplasmsColorectal CancerCRCSeattle Genetics
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.