HER2+ mCRC HER2+ metastatic colorectal cancer
Conditions
Interventions
The study consists of 2 arms. Approximately 400 subjects will be randomized in
a 1:1 fashion to either the tucatinib experimental arm or the standard of care
(SOC) control arm.
Tucatinib experimen
leucovorin or levoleucovorin is administered
concurrently with oxaliplatin via separate IV lines), 5-fluorouracil 400 mg/m2
(IV bolus), then 5-fluorouracil 2400 mg/m2 (IV administration over 46-48
however, individual components within a regim
Sponsors
Seagen Inc., a wholly owned subsidiary of Pfizer
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Inclusion Criteria Participants must meet the following key inclusion criteria to be eligible for the study: • Have histologically and/or cytologically documented adenocarcinoma of the colon or rectum, which is locally advanced unresectable or metastatic • Participants must be willing and able to provide the most recently available formalin fixed paraffin embedded tumor tissue blocks (or freshly sectioned slides, see laboratory manual for details), 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. • 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. • Have 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 testing, tissue must be submitted prior to study enrollment and analyzed within 1 year of biopsy date. • 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 participant has had previous radiation to the target lesion(s), there must be evidence of progression since the radiation • Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 • CNS Inclusion*Based on screening contrast brain magnetic resonance imaging (or CT with contrast if MRI is contraindicated), participants may have any of the following: a. No evidence of brain metastases b. Previously treated brain metastases which are asymptomatic * Brain metastases previously treated with local therapy must not have progressed since treatment * Time since whole brain radiation therapy (WBRT) is >= 14 days prior to enrollment, time since stereotactic radiosurgery (SRS) is >= 7 days prior to enrollment, or time since surgical resection is >= 28 days prior to enrollment * Relevant records of any CNS treatment must be available to allow for classification of target and non target lesions
Exclusion criteria
Exclusion criteria: Exclusion Criteria Participants will be excluded from the study for any of the following key exclusion criteria reasons: • Have previously received any systemic anticancer therapy for CRC in the locally advanced unresectable or metastatic setting or have participated in any interventional clinical trial for 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: participants may have received prior chemotherapy for CRC in the adjuvant setting provided that it was completed >6 months prior to enrollment. • Have previously received radiation therapy within 14 days prior to enrollment (or within 7 days in the setting of SRS). Participants who have received prior radiation therapy must have recovered to baseline from any treatment related adverse events (AEs). Participants who have received palliative radiotherapy for symptomatic metastases may enter the study without a washout period provided that the participant has recovered from any treatment related AEs. • Have previously been treated with anti HER2 therapy • Have ongoing >= Grade 2 diarrhea of any etiology • Inability to swallow pills or any significant GI disease which would preclude the adequate oral absorption of medications • Participants with active CNS metastases (irradiated or resected lesions are permitted, See Inclusion Criteria for details). Participants with carcinomatous meningitis are excluded without exception.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Objective: To compare progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST v1.1) according to blinded independent central review (BICR) assessment between treatment arms. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Objectives: • To compare overall survival (OS) between treatment arms • To compare confirmed objective response rate (cORR) per RECIST v1.1 according to BICR assessment between treatment arms • To assess PFS per RECIST v1.1 according to investigator (INV) assessment • To evaluate cORR per RECIST v1.1 according to INV assessment • To evaluate duration of response (DOR) per RECIST v1.1 according to BICR assessment • To evaluate DOR according to INV assessment • To evaluate time from randomization to disease progression on next-line treatment or death from any cause (PFS2) • To assess the overall safety profiles by the treatment arms • To evaluate the pharmacokinetics (PK) of tucatinib • To assess the change from baseline in selected items of the global health status/quality of life (QoL), physical functioning, and appetite loss by treatment arms using the European Organization for Research and Treatment of Cancer Quality of Life 30-item core questionnaire (EORTC QLQ-C30) • To assess the time to meaningful change in global health status/QoL, physical functioning and appetite loss by treatment arms using the EORTC QLQ-C30 | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, China, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Netherlands, Norway, Poland, Portugal, Slovakia, South Korea, Spain, Switzerland, Taiwan, United Kingdom, United States
Contacts
Public ContactK. Sokolowski
Seagen Inc., a wholly owned subsidiary of Pfizer
Outcome results
None listed