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

• ClinicalTrials.gov Identifier: NCT05253651
• Recruitment Status: Recruiting
• First Posted: February 24, 2022
• Last Update Posted: May 14, 2024
• Sponsor: Seagen Inc.
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Seagen Inc.

Tracking Information

• First Submitted Date: February 14, 2022
• First Posted Date: February 24, 2022
• Last Update Posted Date: May 14, 2024
• Actual Study Start Date: October 24, 2022
• Estimated Primary Completion Date: August 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 14, 2022)

Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by Blinded Independent Central Review (BICR) [ Time Frame: 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 24, 2023)

• Overall survival (OS) [ Time Frame: 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 [ Time Frame: Up to approximately 3 years ]
  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 [ Time Frame: 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 [ Time Frame: Up to approximately 3 years ]
  The proportion of participants with confirmed CR or PR according to RECIST v1.1, as assessed by investigators
• Duration of response (DOR) per RECIST v1.1 by BICR [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Through 30 days after the last study treatment; approximately 1 year ]
• Trough concentration (Ctrough) [ Time Frame: 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 [ Time Frame: Through 30-37 days after the last study treatment; approximately 1 year ]
  Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scores. Scale scores range from 0-100. For functioning and global health status/quality of life (QoL) scales, higher scores indicate better functioning or global health status/quality of life (QoL). For symptom scales, higher scores indicate greater symptom burden.
• Time to meaningful change in EORTC QLQ30 score [ Time Frame: 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 European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scores. Scale scores range from 0-100. For functioning and global health status/QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.

Original Secondary Outcome Measures (submitted: February 14, 2022)

• Overall survival (OS) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Through 30 days after the last study treatment; approximately 1 year ]
• Trough concentration (Ctrough) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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 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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Colorectal Neoplasms

Intervention

• Drug: tucatinib
  300mg given by mouth (orally) twice daily
  Other Name: 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 Name: Herceptin
• Drug: bevacizumab
  5mg/kg given by IV every 2 weeks
  Other Name: 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 Name: 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.

Study Arms

• Experimental: Tucatinib Arm
  Tucatinib + trastuzumab + mFOLFOX6
  Interventions:

  • Drug: tucatinib
  • Drug: trastuzumab
  • Drug: oxaliplatin
  • Drug: leucovorin
  • Drug: levoleucovorin
  • Drug: fluorouracil
• Active Comparator: Standard of Care Arm
  mFOLFOX6 + (bevacizumab OR cetuximab). Either (1) mFOLFOX6, (2) mFOLFOX6 and bevacizumab, or (3) mFOLFOX6 and cetuximab
  Interventions:

  • Drug: bevacizumab
  • Drug: cetuximab
  • Drug: oxaliplatin
  • Drug: leucovorin
  • Drug: levoleucovorin
  • Drug: fluorouracil

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 14, 2022): 400
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 30, 2028
• Estimated Primary Completion Date: August 31, 2025 (Final data collection date for primary outcome measure)

Eligibility 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 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
• GI perforation within 12 months of enrollment

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Seagen Trial Information Support; 866-333-7436; clinicaltrials@seagen.com

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Korea, Republic of, Netherlands, Norway, Poland, Portugal, Slovakia, Spain, Switzerland, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT05253651
• Other Study ID Numbers: SGNTUC-029; 2021-002672-40 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Seagen Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Seagen Inc.
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Monitor; Seagen Inc.

• PRS Account: Seagen Inc.
• Verification Date: May 2024