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

Phase 3RecruitingNCT05253651

Seagen, a wholly owned subsidiary of Pfizer400 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

400

Conditions

Colorectal Neoplasms

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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

Time frame: Up to approximately 3 years

Secondary Outcomes

Overall survival (OS)

The time from randomization to death from any cause

Time frame: Up to approximately 6 years

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

Time frame: Up to approximately 3 years

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

Time frame: Up to approximately 3 years

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

Time frame: Up to approximately 3 years

Duration of response (DOR) per RECIST v1.1 by BICR

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 frame: Up to approximately 3 years

DOR per RECIST v1.1 by investigator assessment

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 frame: Up to approximately 3 years

Time to second progression or death (PFS2)

The time from randomization to disease progression on the next-line of therapy, or death from any cause

Time frame: Up to approximately 3 years

Incidence of adverse events (AEs)

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.

Time frame: Through 30 days after the last study treatment; approximately 1 year

Incidence of dose alterations

Time frame: Through 30 days after the last study treatment; approximately 1 year

Trough concentration (Ctrough)

PK parameter

Time frame: Approximately 4 months

Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQC30) score

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 frame: Through 30-37 days after the last study treatment; approximately 1 year

Time to meaningful change in EORTC QLQ30 score

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.

Time frame: Through 30-37 days after the last study treatment; approximately 1 year

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

Overview

Conditions

Interventions

Eligibility

Locations (378)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts