A Study of Encorafenib Plus Cetuximab With or Without Chemotherapy in People With Previously Untreated Metastatic Colorectal Cancer

Condition(s) studied

Investigational drug(s) / intervention(s)

Encorafenib: 75 mg capsules

Cetuximab: Injection for intravenous use 100 mg/vial, 200 mg/vial, or 500 mg/vial

Oxaliplatin: Powder for solution for intravenous use 50 mg/vial, 100 mg/vial, or 200 mg/vial

Irinotecan: Solution for intravenous infusion 40 mg/vial, 100 mg/vial, or 300 mg/vial

Leucovorin: Injection 50 mg/vial, 100 mg/vial, 200 mg/vial, or 350 mg/vial

5-FU: Injection for intravenous use 250 mg/vial, 500 mg/vial, or 1000 mg/vial

Capecitabine: 150 mg or 500 mg Tablet

Bevacizumab: Optional Injection for intravenous use 100 mg/vial or 400 mg/vial

Study summary

The purpose of this study is to evaluate two study medicines (encorafenib plus cetuximab) taken alone or together with standard chemotherapy for the potential treatment of colorectal cancer that:

* has spread to other parts of the body (metastatic);
* has a certain type of abnormal gene called "BRAF"; and
* has not received prior treatment.

Participants in this study will receive one of the following study treatments:

* Encorafenib plus cetuximab: These participants will receive encorafenib by mouth at home every day and cetuximab once every two weeks by intravenous (IV) infusion (an injection into the vein) at the study clinic.
* Encorafenib plus cetuximab with chemotherapy: These participants will receive encorafenib and cetuximab in the way described in the bullet above. Additionally, they will receive standard chemotherapy by IV infusion and oral treatment at home.
* Chemotherapy alone: These participants will receive chemotherapy, the standard treatment for this condition, by IV infusion at the study clinics and oral treatment at home.

This study is currently enrolling participants who will receive either encorafenib plus cetuximab with chemotherapy or chemotherapy alone.

The study team will monitor how each participant responds to the study treatment for up to about 3 years.

Eligibility

Primary outcome measure(s)

• SLI: Number of Participants With Dose Limiting Toxicity (DLTs) — Cycle 1 (28 days)
  DLT: Any AE/lab value during first 28 days (D) of treatment that met at least 1 criteria: AE/lab value unrelated to underlying disease,PD,intercurrent illness,concomitant medications resulting in inability to tolerate atleast 75% of planned dose intensity of study drug,fatigue grade (G)3\>14 consecutive D, interstitial lung disease G\>=2,rash,hand foot skin reaction G3\>14 consecutive D or G4,diarrhea G3 \>=48 hours or G4,nausea/vomiting G3\>=48 hours or G4,mucositis G\>=3,total bilirubin G\>=3, aspartate aminotransferase/alanine aminotransferase G\>=3 in conjunction with total bilirubin G\>=2 or G3 \>7 consecutive D or G4,Serum creatinine G\>=3,absolute neutrophil count G4 \>7 consecutive D, \>=G3 febrile neutropenia,G3 platelet count decreased with signs of bleeding,platelet count G4,ECG QTcF prolonged \>=G3,G\>=3 uveitis \>21 consecutive D,G4 confirmed by ophthalmic examination,paresthesia/dysesthesias G\>=3,other G\>=3 hematologic/nonhematologic toxicity except lymphocyte count decreased G\>=3.
• Phase 3: Progression Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) for Arm B vs Arm C - FAS — From date of randomization to earliest documentation of PD by BICR or death or censoring date, whichever occurred first (maximum up to 37.25 months)
  PFS was defined as the time from date of randomization to earliest documented disease progression (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or death due to any cause as assessed by BICR. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 millimeter (mm) for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion. Censoring details: no adequate baseline assessment, including no disease at baseline: participants were censored to randomization date; no PD, lost to follow-up, withdrawal of consent, PD or death \>12 (or 16) weeks after the last adequate tumor assessment, and start of new anticancer treatment: participants were censored to last adequate tumor assessment documenting no PD prior to new anticancer therapy, or missed assessments. Analysis was performed using Kaplan Meier method.
• Phase 3: Objective Response Rate (ORR) as Assessed by BICR for Arm B vs Arm C - FAS ORR Subset — From date of randomization to until documented PD by BICR, or start of subsequent anticancer therapy or death, whichever occurred first (maximum up to 24.71 months)
  ORR was defined as the percentage of participants who achieved best overall response (BOR) of confirmed complete response (CR) or partial response (PR) according to RECIST v 1.1 as assessed by BICR. CR: complete disappearance of all target lesions (with the exception of nodal disease) and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
• Cohort 3: ORR as Assessed by BICR for Arm D vs Arm E - FAS — From date of randomization until documented PD by BICR, or start of subsequent anticancer therapy or death, whichever occurred first (maximum up to 14.1 months)
  ORR was defined as the percentage of participants who achieved BOR of confirmed CR or PR according to RECIST v 1.1 as assessed by BICR. CR: complete disappearance of all target lesions (with the exception of nodal disease) and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.

Trial sites (272)

+ 232 more sites — see the full list on the official registry below.

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