TUCATINIB for Metastatic colorectal cancer | HER2-positive colorectal cancer

Inclusion criteria

• {"criterion_text":"- Have histologically and/or cytologically documented adenocarcinoma of the colon or rectum, which is locally advanced unresectable or metastatic"}
• {"criterion_text":"- Participants must be willing and able to provide the most recently available formalin-fixed paraffin-embedded tumor tissue blocks obtained prior to treatment initiation, to a sponsor-designated central laboratory for biomarker analysis. If archival tissue is not available, then a newly-obtained baseline biopsy of an accessible tumor lesion is required within 35 days prior to the Cycle 1 Day 1 timeframe. Biopsy must provide adequate tissue for analysis; the following biopsy types are acceptable: resection, excision, punch (skin lesions only) and core needle biopsies."}
• {"criterion_text":"- Have HER2+ disease as determined by tissue-based investigational HER2 IHC and ISH assays performed at a sponsor-defined central laboratory. HER2 amplification will be determined using ASCO/CAP guidelines for gastric and gastroesophageal cancer with IHC 3+ or IHC 2+/ISH+ result."}
• {"criterion_text":"- H4.\tHave RAS WT disease as determined by local or central testing. Central testing may only be used with Medical Monitor approval if local testing is not available or when otherwise deemed necessary. For central RAS analysis, tissue sample must be analyzed within 1 year of biopsy date."}
• {"criterion_text":"- Have radiographically measurable disease per RECIST v1.1 according to INV assessment, with at least one site of disease that is measurable and that has not been previously irradiated; or, if the subject has had previous radiation to the target lesion(s), there must be evidence of progression since the radiation"}
• {"criterion_text":"- Have ECOG Performance Status (PS) of 0 or 1"}
• {"criterion_text":"- CNS Inclusion: a.\tNo evidence of brain metastases; b.\tPreviously treated brain metastases which are asymptomatic."}

Exclusion criteria

• {"criterion_text":"- Have previously received any systemic anticancer therapy for CRC in the metastatic setting or have participated in any interventional clinical trial for CRC in the metastatic setting; note that subjects may have received a maximum of 2 doses of mFOLFOX6 in the locally advanced/unresectable or metastatic setting prior to randomization. Participants may have received prior chemotherapy for CRC in the adjuvant setting provided that it was completed >6 months prior to enrollment."}
• {"criterion_text":"- Have previously received radiation therapy within 14 days prior to enrollment (or within 7 days in the setting of SRS). SubjectsParticipants who have received prior radiation therapy must have recovered to baseline from any treatment-related adverse events (AEs). Participants Subjects who have received palliative radiotherapy for symptomatic metastases may enter the study without a washout period provided that the subject has recovered from any treatment-related AEs."}
• {"criterion_text":"- Have previously been treated with anti-HER2 therapy"}
• {"criterion_text":"- Have ongoing ≥ Grade 2 diarrhea of any etiology"}
• {"criterion_text":"- Inability to swallow pills or any significant GI disease which would preclude the adequate oral absorption of medications"}
• {"criterion_text":"- Participants with active CNS metastases (irradiated or resected lesions are permitted). See Inclusion Criteria for details. Participants with carcinomatous meningitis are excluded without exception."}

Primary endpoints

• {"endpoint_text":"- PFS per BICR is defined as the time from the date of randomization to the BICR assessment of disease progression according to RECIST v1.1 or death from any cause, whichever occurs first","definition_or_measurement_approach":"PFS per BICR is defined as the time from the date of randomization to the BICR assessment of disease progression according to RECIST v1.1 or death from any cause, whichever occurs first"}

Secondary endpoints

• {"endpoint_text":"- OS, defined as time from randomization to death from any cause (key secondary endpoint)","definition_or_measurement_approach":"OS defined as time from randomization to death from any cause"}
• {"endpoint_text":"- cORR per BICR is defined as the proportion of participants with confirmed CR or PR according to RECIST v1.1, as assessed by BICR. (key secondary endpoint)","definition_or_measurement_approach":"Proportion of participants with confirmed complete response (CR) or partial response (PR) per RECIST v1.1 assessed by BICR"}
• {"endpoint_text":"- PFS per INV is defined as time from the date of randomization to the investigator assessment of disease progression according to RECIST v1.1 or death from any cause, whichever occurs first","definition_or_measurement_approach":"Time from randomization to investigator-assessed disease progression per RECIST v1.1 or death"}
• {"endpoint_text":"- cORR per INV is defined as the proportion of participants with confirmed CR or PR according to RECIST v1.1, as assessed by investigators.","definition_or_measurement_approach":"Proportion of participants with confirmed CR or PR per RECIST v1.1 assessed by investigators"}
• {"endpoint_text":"- DOR is defined as 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, whichever occurs earlier.","definition_or_measurement_approach":"Time from first documented objective response to first documentation of disease progression per RECIST v1.1 or death"}
• {"endpoint_text":"- DOR per investigator is based on investigator response assessment and DOR per BICR is based on BICR response.","definition_or_measurement_approach":"DOR determined separately by investigator assessment and by BICR"}
• {"endpoint_text":"- Time to second progression or death (PFS2) is defined as the time from randomization to disease progression on the next-line of therapy, or death from any cause, whichever occurs first","definition_or_measurement_approach":"Time from randomization to progression on next-line therapy or death"}
• {"endpoint_text":"- Individual plasma tucatinib concentrations will be used for PK assessments","definition_or_measurement_approach":"Individual plasma concentrations of tucatinib will be measured and used for PK assessments"}
• {"endpoint_text":"- Change from baseline will be measured for the following PROs scales: global health status/QoL (EORTC QLQ-C30 items 29 and 30) and physical functioning (EORTC QLQ-C30 items 1-5) and time to meaningful change, defined as the time from baseline to the first onset of a ≥10-point changes from baseline in global health status/QoL (EORTC QLQ-C30 items 29 and 30), physical functioning (EORTC QLQ-C30 items 1-5)","definition_or_measurement_approach":"Change from baseline on EORTC QLQ-C30 items 29-30 (global health/QoL) and items 1-5 (physical functioning); time to meaningful change defined as first onset of ≥10-point change from baseline"}

Methods

• Patient email (country-specific patient email recruitment materials provided, documented as K2_1_Recruitment Material_Patient Email files)
• Patient brochure (country-specific patient brochure recruitment materials provided, documented as K2_2_Recruitment Material_Patient Brochure files)
• Sponsor / site websites (OUS Website recruitment material documented as K2_3_Recruitment Material_OUS Website files)
• Regional image/library materials (K2_4_Regional Image library files)
• Local site recruitment and third-party site support (documents and site-level Scout Clinical materials listed for some countries)

Primary sponsor

Full Name

Seagen Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

Management of lab safety data

Name

Parexel International (IRL) Limited

Name

Ppd Inc.

Name

QPS LLC

Name

Continuum Clinical LLC

Responsibilities

subject recruitment and retention services

Name

4g Clinical LLC

Name

WCG Clinical Inc.

Responsibilities

Site support and staffing

Third parties

• {"country":"United States","full_name":"Cytel Inc.","duties_or_roles":"Independent Data Monitoring Committee","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Alturas Analytics Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Subject reimbursement, subject recruitment and meeting planning","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Management of lab safety data","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Transperfect Translations International Inc.","duties_or_roles":"Translations","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Imperial Clinical Research Services International Limited","duties_or_roles":"Subject recruitment and retention; printing and shipping","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Imaging","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"Site support and staffing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"QPS LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Continuum Clinical LLC","duties_or_roles":"subject recruitment and retention services","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Ppd Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Alpha Solutions USA LLC","duties_or_roles":"Web site maintenance","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"ePRO","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Discovery Life Sciences Biomarker Services GmbH","duties_or_roles":"","organisation_type":"Pharmaceutical company"}