MOUNTAINEER-03: A Study of Tucatinib With Trastuzumab and mFOLFOX6 Versus Standard of Care Treatment in First-line HER2+ Metastatic Colorectal Cancer

Sponsor

Seagen Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05253651

Collaborator

Merck Sharp & Dohme LLC (Industry)

400

Enrollment

Locations

Arms

Anticipated Duration (Months)

28.6

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief 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 test 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 a group to the tucatinib 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 These are drugs that are used to treat this type of cancer.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Neoplasms	Drug: tucatinib Drug: trastuzumab Drug: bevacizumab Drug: cetuximab Drug: oxaliplatin Drug: leucovorin Drug: levoleucovorin Drug: fluorouracil	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Aug 31, 2022

Anticipated Primary Completion Date :

Aug 31, 2025

Anticipated Study Completion Date :

Apr 30, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tucatinib Arm Tucatinib + trastuzumab + mFOLFOX6	Drug: tucatinib 300mg given by mouth (orally) twice daily Other Names: TUKYSA, ONT-380, ARRY-380 Drug: 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. Other Names: Herceptin Drug: oxaliplatin 85mg/m2 given by IV every 2 weeks. Component of mFOLFOX6. Drug: leucovorin 400mg/ m2 given by IV every 2 weeks. Component of mFOLFOX6. Drug: levoleucovorin 200mg/ m2 given by IV every 2 weeks. May be given in place of leucovorin. Component of mFOLFOX6. Drug: 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.
Active Comparator: Standard of Care Arm mFOLFOX6 + (bevacizumab OR cetuximab). Either (1) mFOLFOX6, (2) mFOLFOX6 and bevacizumab, or (3) mFOLFOX6 and cetuximab	Drug: bevacizumab 5mg/kg given by IV every 2 weeks Other Names: Avastin Drug: cetuximab 400mg/m2 loading dose will be given by IV on Cycle 1 day 1, followed by 250mg/m2 given by IV weekly Other Names: Erbitux Drug: oxaliplatin 85mg/m2 given by IV every 2 weeks. Component of mFOLFOX6. Drug: leucovorin 400mg/ m2 given by IV every 2 weeks. Component of mFOLFOX6. Drug: levoleucovorin 200mg/ m2 given by IV every 2 weeks. May be given in place of leucovorin. Component of mFOLFOX6. Drug: 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.

Arm

Intervention/Treatment

Experimental: Tucatinib Arm

Tucatinib + trastuzumab + mFOLFOX6

Drug: tucatinib

300mg given by mouth (orally) twice daily

Other Names:

TUKYSA, ONT-380, ARRY-380

Drug: 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.

Other Names:

Herceptin

Drug: oxaliplatin

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

Drug: leucovorin

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

Drug: levoleucovorin

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

Drug: 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.

Active Comparator: Standard of Care Arm

mFOLFOX6 + (bevacizumab OR cetuximab). Either (1) mFOLFOX6, (2) mFOLFOX6 and bevacizumab, or (3) mFOLFOX6 and cetuximab

Drug: bevacizumab

5mg/kg given by IV every 2 weeks

Other Names:

Avastin

Drug: cetuximab

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

Other Names:

Erbitux

Drug: oxaliplatin

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

Drug: leucovorin

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

Drug: levoleucovorin

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

Drug: 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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Overall survival (OS) [Up to approximately 6 years]
The time from randomization to death from any cause
Confirmed objective response rate (cORR) per RECIST v1.1 by BICR [Up to approximately 3 years]
The proportion of subjects 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 [Up to approximately 3 years]
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 [Up to approximately 3 years]
The proportion of subjects with confirmed CR or PR according to RECIST v1.1, as assessed by investigators
Duration of response (DOR) per RECIST v1.1 by BICR [Up to approximately 3 years]
The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of disease progression per RECIST v1.1 or death from any cause
DOR per RECIST v1.1 by investigator assessment [Up to approximately 3 years]
The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of disease progression per RECIST v1.1 or death from any cause
Time to second progression or death (PFS2) [Up to approximately 3 years]
The time from randomization to disease progression on the next-line of therapy, or death from any cause
Incidence of adverse events (AEs) [Through 30 days after the last study treatment; approximately 1 year]
Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Incidence of dose alterations [Through 30 days after the last study treatment; approximately 1 year]
Trough concentration (Ctrough) [Approximately 4 months]
PK parameter
Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQC30) score [Through 30-37 days after the last study treatment; approximately 1 year]
The EORTC questionnaires measure aspects of health-related quality of life (HRQoL).
Time to meaningful change in EORTC QLQ30 score [Through 30-37 days after the last study treatment; approximately 1 year]
The time from baseline to the first onset of a ≥10-point changes in global health status/quality of life (QoL)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically and/or cytologically confirmed adenocarcinoma of the colon or rectum which is metastatic and/or unresectable
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
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 metastatic setting
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
GI perforation within 12 months of enrollment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pacific Cancer Medical Center	Anaheim	California	United States	92801
2	Los Angeles Cancer Network	Los Angeles	California	United States	90017
3	Kaiser Permanente Southern California	Los Angeles	California	United States	90027
4	Saint Joseph Heritage Medical Group	Santa Rosa	California	United States	95403
5	HealthPartners Institute	Saint Louis Park	Minnesota	United States	55416
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Gabrail Cancer Center Research, LLC	Canton	Ohio	United States	44718
8	Providence Portland Medical Center	Portland	Oregon	United States	97213
9	US Oncology Investigational Products Center (IPC)	Irving	Texas	United States	75063
10	Texas Oncology - McKinney	McKinney	Texas	United States	75071
11	Texas Oncology - Paris	Paris	Texas	United States	75460
12	US Oncology Central Regulatory	The Woodlands	Texas	United States	77380
13	Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care	Roanoke	Virginia	United States	24014
14	Northwest Cancer Specialists, P.C.	Vancouver	Washington	United States	98684