Neoplasms
Conditions
Interventions
Drug: Encorafenib
75 mg capsules
Other Name: Braftovi, PF-07263896, LGX818, ONO-7702
Drug: Cetuximab
Injection for intravenous use 100 mg/vial, 200 mg/vial, or 500 mg/vial
Other Name: Erbitux
Drug
Sponsors
Kawai Norisuke
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria: * Safety Lead-In = Male/female >= 18 years old * Phase 3 and Cohort 3: Male/female >= 16 years old (where permitted locally) * Histologically or cytologically confirmed Stage IV CRC that contains BRAF V600E mutation * Prior systemic treatment in metastatic setting: 0-1 regimens for Safety Lead In; none for Phase 3 and Cohort 3. (Note: Prior adjuvant or neoadjuvant therapy considered metastatic treatment if relapse/metastasis < 6 month from end of adj/neoadjuvant treatment ) * Measurable disease (Phase 3 and Cohort 3)/ Measurable or evaluable disease (Safety Lead-in) * ECOG PS 0-1 * Adequate organ function
Exclusion criteria
Exclusion criteria: Exclusion Criteria: * Tumors that are locally confirmed MSI-H or dMMR unless participant is ineligible to receive immune checkpoint inhibitors due to a pre-existing medical condition * Active bacterial or viral infections in 2 weeks prior to starting dosing * Symptomatic brain metastases
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Outcome Measures : 1.Safety Lead-in Study: Incidence of Dose Limiting Toxicities (DLTs) [ Time Frame: After 30 evaluable patients in each cohort complete 1 cycle (up to 28 days), approximately 12 months ] Incidence of dose limiting toxicity defined as any adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, disease progression, intercurrent illness or concomitant medications/therapies occurring during the first 28 days of treatment 2.Phase 3: Progression free survival, by blinded independent review [ Time Frame: Duration of Phase 3, approximately 36 months ] Progression free survival, defined as the time from the date of randomization to the earliest documented disease progression or death due to any cause: encorafenib and cetuximab + (Arm A) vs Control Arm (Arm C) and encorafenib and cetuximab + mFOLFOX6 or encorafenib + cetuximab + FOLFIRI (Arm B) vs the Control Arm (Arm C) 3.Phase 3: Objective response rate by blinded independent review [ Time Frame: Duration of Phase 3, approximately 23 months ] Objective response defined as complete response (CR), or partial response (PR) according to RECIST v1.1 based on BICR assessment, from the date of randomization until the date of the first documentation of progression of disease (PD) 4.Cohort 3: Objective response rate by blinded independent review [ Time Frame: Duration of Cohort 3, approximately 15 months ] Defined as CR, or PR according to RECIST v1.1 based on BICR assessment, from the date of randomization until the date of the first documentation of PD, death or start of new anticancer therapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety Lead-in: Incidence of adverse events, Incidence of abnormal clinical laboratory parameters, abnormal vital signs and abnormal electrocardiograms, Incidence of dose interruptions, dose modifications and discontinuations due to adverse events, etc. Phase 3 and Cohort 3: Overall survival, Overall response rate by Investigator, Duration of response by blinded independent review and by Investigator, etc. | — |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Czechia, Denmark, Finland, Germany, India, Italy, Japan, Mexico, Netherlands, New Zealand, Norway, Poland, Russia, Slovakia, South Africa, South Korea, Spain, Sweden, Taiwan, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trials Information Desk
Pfizer R&D Japan G.K.
Outcome results
None listed