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.
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.
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
Parallel
tucatinib
Drug300mg given by mouth (orally) twice daily
trastuzumab
Drug8mg/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
Drug5mg/kg given by IV every 2 weeks
cetuximab
Drug400mg/m2 loading dose will be given by IV on Cycle 1 day 1, followed by 250mg/m2 given by IV weekly
oxaliplatin
Drug85mg/m2 given by IV every 2 weeks. Component of mFOLFOX6.
leucovorin
Drug400mg/ m2 given by IV every 2 weeks. Component of mFOLFOX6.
levoleucovorin
Drug200mg/ m2 given by IV every 2 weeks. May be given in place of leucovorin. Component of mFOLFOX6.
fluorouracil
Drug400mg/m2 given by IV bolus then 2400mg/m2 given by continuous IV infusion (over 46-48 hours) every 2 weeks. Component of mFOLFOX6.
Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by Blinded Independent Central Review (BICR)
The time from the date of randomization to the BICR assessment of disease progression according to RECIST v1.1 or death from any cause
Overall survival (OS)
The time from randomization to death from any cause
Confirmed objective response rate (cORR) per RECIST v1.1 by BICR
The proportion of participants with confirmed complete response (CR) or partial response (PR) according to RECIST v1.1, as assessed by BICR
PFS per RECIST v1.1 by investigator assessment
The time from the date of randomization to the investigator assessment of disease progression according to RECIST v1.1 or death from any cause
cORR per RECIST v1.1 by investigator assessment
The proportion of participants with confirmed CR or PR according to RECIST v1.1, as assessed by investigators
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