A Study of Tucatinib With Trastuzumab and mFOLFOX6 Versus Standard of Care Treatment in First-line HER2+ Metastatic Colorectal Cancer

NCT05253651 · tracked via the Priya Life Science USA tracker

Sponsor

Seagen, a wholly owned subsidiary of Pfizer

Phase

Phase 3

Started

2022-10-24

Last updated

2026-07-22

Condition(s) studied

Colorectal Neoplasms

Investigational drug(s) / intervention(s)

tucatinibtrastuzumabbevacizumabcetuximaboxaliplatinleucovorinlevoleucovorinfluorouracil

tucatinib: 300mg given by mouth (orally) twice daily

trastuzumab: 8mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 day 1, followed by 6mg/kg given by IV every 3 weeks thereafter.

bevacizumab: 5mg/kg given by IV every 2 weeks

cetuximab: 400mg/m2 loading dose will be given by IV on Cycle 1 day 1, followed by 250mg/m2 given by IV weekly

oxaliplatin: 85mg/m2 given by IV every 2 weeks. Component of mFOLFOX6.

leucovorin: 400mg/ m2 given by IV every 2 weeks. Component of mFOLFOX6.

levoleucovorin: 200mg/ m2 given by IV every 2 weeks. May be given in place of leucovorin. Component of mFOLFOX6.

fluorouracil: 400mg/m2 given by IV bolus then 2400mg/m2 given by continuous IV infusion (over 46-48 hours) every 2 weeks. Component of mFOLFOX6.

Study summary

This study is being done to find out if tucatinib with other cancer drugs works better than standard of care to treat participants with HER2 positive colorectal cancer. This study will also determine what side effects happen when participants take this combination of drugs. A side effect is anything a drug does to the body besides treating your disease.

Participants in this study have colorectal cancer that has spread through the body (metastatic) and/or cannot be removed with surgery (unresectable).

Participants will be assigned randomly to the tucatinib group or standard of care group. The tucatinib group will get tucatinib, trastuzumab, and mFOLFOX6. The standard of care group will get either:

* mFOLFOX6 alone,
* mFOLFOX6 with bevacizumab, or
* mFOLFOX6 with cetuximab mFOLFOX6 is a combination of multiple drugs. All of the drugs given in this study are used to treat this type of cancer.

Eligibility

Sex

ALL

Min age

18 Years

Max age

—

Healthy volunteers

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.

Primary outcome measure(s)

Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by Blinded Independent Central Review (BICR) — Up to approximately 3 years
The time from the date of randomization to the BICR assessment of disease progression according to RECIST v1.1 or death from any cause

Trial sites (366)

Facility	City	Region	Status
Palo Verde Hematology Oncology	Glendale	Arizona	Recruiting
Mayo Clinic Building - Phoenix	Phoenix	Arizona	Recruiting
Mayo Clinic Hospital	Phoenix	Arizona	Recruiting
Mayo Clinic	Scottsdale	Arizona	Recruiting
Los Angeles Cancer Network - Anaheim	Anaheim	California	Recruiting
Kaiser Permanente Anaheim Kraemer Medical Offices	Anaheim	California	Active Not Recruiting
Kaiser Permanente Baldwin Park Medical Center	Baldwin Park	California	Active Not Recruiting
Kaiser Permanente Bellflower Medical Offices	Bellflower	California	Active Not Recruiting
Kaiser Permanente Fontana Medical Center	Fontana	California	Active Not Recruiting
Los Angeles Cancer Network - Fountain Vally	Fountain Valley	California	Recruiting
Los Angeles Cancer Network - Corporate Office	Glendale	California	Recruiting
Los Angeles Hematology Oncology Medical Group	Glendale	California	Recruiting
Los Angeles Hematology Oncology Medical Group	Glendale	California	Recruiting
Kaiser Permanente South Bay Medical center	Harbor City	California	Active Not Recruiting
Kaiser Permanente Alton/Sand Canyon Medical Offices	Irvine	California	Active Not Recruiting
Los Angeles Hematology Oncology Medical Group	Los Angeles	California	Recruiting
USC Norris Koreatown - Medical Oncology	Los Angeles	California	Terminated
Kaiser Permanente Los Angeles Medical Offices	Los Angeles	California	Active Not Recruiting
Keck Hospital of USC	Los Angeles	California	Terminated
Los Angeles General Medical Center	Los Angeles	California	Terminated
University of Southern California	Los Angeles	California	Terminated
USC/Norris Comprehensive Cancer Center	Los Angeles	California	Terminated
Kaiser Permanente West Los Angeles Medical Center	Los Angeles	California	Active Not Recruiting
USC Norris Oncology/Hematology - Newport Beach	Newport Beach	California	Terminated
Kaiser Permanente Ontario Medical Center	Ontario	California	Active Not Recruiting
Kaiser Permanente Panorama City Medical Center	Panorama City	California	Active Not Recruiting
Keck Medical Center of USC Pasadena	Pasadena	California	Terminated
Los Angeles Hematology Oncology Medical Group	Pasadena	California	Recruiting
Kaiser Permanente Riverside Medical Center	Riverside	California	Active Not Recruiting
Kaiser Permanente San Diego Mission Road (Regulatory and Lab Supplies)	San Diego	California	Active Not Recruiting
Kaiser Permanente Zion Medical Center	San Diego	California	Active Not Recruiting
Kaiser Permanente San Marcos Medical Offices	San Marcos	California	Active Not Recruiting
Los Angeles Hematology Oncology Medical Group	Van Nuys	California	Recruiting
Kaiser Permanente Woodland Hills Medical Center	Woodland Hills	California	Active Not Recruiting
Rocky Mountain Cancer Centers, LLP	Aurora	Colorado	Recruiting
Rocky Mountain Cancer Centers, LLP	Boulder	Colorado	Recruiting
Rocky Mountain Cancer Centers, LLP	Colorado Springs	Colorado	Recruiting
Rocky Mountain Cancer Centers, LLP	Denver	Colorado	Recruiting
Rocky Mountain Cancer Centers, LLP	Denver	Colorado	Recruiting
Rocky Mountain Cancer Centers, LLP	Lakewood	Colorado	Recruiting

+ 326 more sites — see the full list on the official registry below.

On this site

📄 Herceptin (trastuzumab) drug profile → 📄 Avastin (bevacizumab) drug profile →

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05253651 on ClinicalTrials.gov ↗ ← All trials in the USA