Phase 2
N=107
A Study Evaluating the Combination of Encorafenib and Cetuximab Versus Irinotecan/Cetuximab or Infusional 5-fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab in Chinese Patients With BRAF V600E Mutant Metastatic Colorectal Cancer.
BRAF V600E · Metastatic Colorectal Cancer
Bottom Line
View on ClinicalTrials.gov: NCT05004350 ↗Enrolled (actual)
107
Serious AEs
24.3%
Results posted
Apr 2026
Primary outcome: Primary: Safety Lead-in Phase (SLI): Incidence of Dose Limiting Toxicities (DLTs) — 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Encorafenib (Drug); Cetuximab (Drug); FOLFIRI (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Pierre Fabre Medicament
- Primary completion
- Dec 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Safety Lead-in Phase (SLI): Incidence of Dose Limiting Toxicities (DLTs) |
— | — |
| PRIMARY Randomized Phase 2: Progression-free Survival (PFS) by Blinded (to Treatment Received) Independent Central Review (BICR) at the Primary Completion Date |
4.2; 2.5 | 0.0004 sig |
| PRIMARY Randomized Phase 2: Progression-free Survival (PFS) by Blinded (to Treatment Received) Independent Central Review (BICR) at the Final Analysis |
4.2; 2.5 | 0.0004 sig |
| SECONDARY Safety Lead-in Phase: Confirmed Objective Response Rate (cORR) Per BICR |
30 | — |
| SECONDARY Safety Lead-in Phase: Confirmed Objective Response Rate (cORR) Per Investigator |
30 | — |
| SECONDARY Safety Lead-in Phase: Duration of Response (DOR) Per BICR |
12.5 | — |
| SECONDARY Safety Lead-in Phase: Duration of Response (DOR) Per Investigator |
7 | — |
| SECONDARY Safety Lead-in Phase: Overall Duration of Exposure to Study Treatment |
16.50 | — |
| SECONDARY Safety Lead-in Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
10 | — |
| SECONDARY Safety Lead-in Phase: Number of Participants With Serious TEAEs |
1 | — |
| SECONDARY Safety Lead-in Phase: Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to Adverse Events (AEs) |
3; 3; 1 | — |
| SECONDARY Safety Lead-in Phase: Number of Participants With Clinically Notable Vital Sign Abnormalities |
1; 0; 1; 0; 2 | — |
| SECONDARY Safety Lead-in Phase: Number of Participants With Clinically Notable Electrocardiogram (ECG) Values |
4; 0; 0; 0; 0; 4 | — |
| SECONDARY Safety Lead-in Phase: Number of Participants With Clinically Notable Shifts in Hematology and Coagulation Laboratory Parameters |
2; 0; 0; 0; 0; 0 | — |
| SECONDARY Safety Lead-in Phase: Number of Participants With Clinically Notable Shifts in Serum Chemistry Laboratory Parameters |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Safety Lead-in Phase: Number of Participants With Notable Dermatological Abnormalities |
1; 0; 0; 8 | — |
| SECONDARY Safety Lead-in Phase: Measurement of Performance Status Using the Eastern Co-operative Oncology Group (ECOG) Scale |
1; 9 | — |
| SECONDARY Safety Lead-in Phase: Evaluation of the Plasma Concentrations of Encorafenib |
NA; 1730; 4120; 4290; 1970; 11.4 | — |
| SECONDARY Safety Lead-in Phase: Evaluation of the Serum Concentrations of Cetuximab |
NA; 71800; 161000; 240000; 220000; 47400 | — |
| SECONDARY Safety Lead-in Phase: Evaluation of the Area Under the Curve (AUC) Derived From Plasma Concentration of Encorafenib |
18200; 18600; 9760; 12500; 9870 | — |
| SECONDARY Safety Lead-in Phase: Evaluation of the Area Under the Curve (AUC) Derived From Serum Concentration of Cetuximab |
988000; 1000000; 987000; 989000 | — |
| SECONDARY Safety Lead-in Phase: Evaluation of the Maximum Concentration (Cmax) Derived From Plasma Concentration of Encorafenib |
5430; 4210 | — |
| SECONDARY Safety Lead-in Phase: Evaluation of the Maximum Concentration (Cmax) Derived From Serum Concentration of Cetuximab |
244000; 209000 | — |
| SECONDARY Safety Lead-in Phase: Evaluation of the Minimum Concentration (Cmin) Derived From Plasma Concentration of Encorafenib |
11.4 | — |
| SECONDARY Safety Lead-in Phase: Evaluation of the Minimum Concentration (Cmin) Derived From Serum Concentration of Cetuximab |
47400 | — |
| SECONDARY Randomized Phase 2: Progression-free Survival (PFS) by Investigator |
4.2; 2.5 | <0.0001 sig |
| SECONDARY Randomized Phase 2: Confirmed Objective Response Rate (cORR) in ENCO + CETUX Arm vs Control Arm Per BICR |
23.1; 6.3 | — |
| SECONDARY Randomized Phase 2: Confirmed Objective Response Rate (cORR) in ENCO + CETUX Arm vs Control Arm Per Investigator |
27.7; 6.3 | — |
| SECONDARY Randomized Phase 2: Duration of Response (DOR) in ENCO + CETUX Arm vs Control Arm Per BICR |
5.6; NA | — |
| SECONDARY Randomized Phase 2: Duration of Response (DOR) in ENCO + CETUX Arm vs Control Arm Per Investigator |
4.0; NA | — |
| SECONDARY Randomized Phase 2: Confirmed Disease Control Rate (cDCR) in ENCO + CETUX Arm vs Control Arm Per BICR |
75.4; 28.1 | — |
| SECONDARY Randomized Phase 2: Confirmed Disease Control Rate (cDCR) in ENCO + CETUX Arm vs Control Arm Per Investigator |
78.5; 37.5 | — |
| SECONDARY Randomized Phase 2: Time to Response (TTR) in ENCO + CETUX Arm vs Control Arm Per BICR |
1.4; 1.5 | — |
| SECONDARY Randomized Phase 2: Time to Response (TTR) in ENCO + CETUX Arm vs Control Arm Per Investigator |
1.5; 1.6 | — |
| SECONDARY Randomized Phase 2: Overall Survival (OS) |
11.9; 8.2 | 0.0075 sig |
| SECONDARY Randomized Phase 2: Overall Duration of Exposure to Study Treatment |
18.90; 8.00 | — |
| SECONDARY Randomized Phase 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
65; 27 | — |
| SECONDARY Randomized Phase 2: Number of Participants With Serious TEAEs |
20; 5 | — |
| SECONDARY Randomized Phase 2: Number of Participants With Clinically Notable Vital Sign Abnormalities |
2; 0; 1; 0; 2; 1 | — |
| SECONDARY Randomized Phase 2: Number of Participants With Clinically Notable Electrocardiogram (ECG) Values |
37; 2; 7; 1; 2; 1 | — |
| SECONDARY Randomized Phase 2: Number of Participants With Clinically Notable Shifts in Hematology and Coagulation Laboratory Parameters |
7; 7; 0; 0; 2; 13 | — |
| SECONDARY Randomized Phase 2: Number of Participants With Clinically Notable Shifts in Serum Chemistry Laboratory Parameters |
3; 0; 3; 1; 3; 0 | — |
| SECONDARY Randomized Phase 2: Number of Participants With Notable Dermatological Abnormalities |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Randomized Phase 2: Measurement of Performance Status Using the Eastern Co-operative Oncology Group (ECOG) Scale |
17; 5; 46; 15; 0; 1 | — |
| SECONDARY Randomized Phase 2: Time to Definitive Deterioration in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients (EORTC QLQ-C30) Questionnaire Scores |
NA; 2.5 | — |
| SECONDARY Randomized Phase 2: Time to Definitive Deterioration in the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire |
8.0; 4.2 | — |
| SECONDARY Randomized Phase 2: Time to Definitive Deterioration in the Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) Questionnaire |
22.1; 2.5 | — |
| SECONDARY Randomized Phase 2: Evolution in the Patient Global Impression of Change (PGIC) Questionnaire |
7; 0; 29; 3; 15; 9 | — |
| SECONDARY Randomized Phase 2: Evaluation of the Plasma Concentrations of Encorafenib |
NA; 2490; 3850; 3330; 2180; NA | — |
| SECONDARY Randomized Phase 2: Evaluation of the Serum Concentrations of Cetuximab |
NA; 82500; 175000; 222000; 207000; 53000 | — |
| SECONDARY Randomized Phase 2: Evaluation of the Area Under the Curve (AUC) Derived From Plasma Concentration of Encorafenib |
18400; 18800; 8670; 10800; 8710 | — |
| SECONDARY Randomized Phase 2: Evaluation of the Area Under the Curve (AUC) Derived From Serum Concentration of Cetuximab |
927000; 927000; 994000; 990000 | — |
| SECONDARY Randomized Phase 2: Evaluation of the Minimum Concentration (Cmin) Derived From Plasma Concentration of Encorafenib |
NA; 7.75 | — |
| SECONDARY Randomized Phase 2: Evaluation of the Minimum Concentration (Cmin) Derived From Serum Concentration of Cetuximab |
NA; 53000 | — |
| SECONDARY Randomized Phase 2: Evaluation of the Maximum Concentration (Cmax) Derived From Plasma Concentration of Encorafenib |
5610; 3700 | — |
| SECONDARY Randomized Phase 2: Evaluation of the Maximum Concentration (Cmax) Derived From Serum Concentration of Cetuximab |
230000; 197000 | — |
Summary
Encorafenib is currently being developed (with or without binimetinib), in combination with cetuximab, for the treatment of adult patients with B-RAF proto-oncogene, serine/threonine kinase V600E mutant (BRAF V600E) metastatic colorectal cancer (mCRC), who have received prior systemic therapy.
Eligibility Criteria
Inclusion Criteria for Molecular Prescreening:
The following inclusion criteria must be met for a participant to be eligible to undergo molecular tumor prescreening:
- Chinese male or female participant with age ≥18 years at the time of informed consent.
- Histologically- or cytologically-confirmed colorectal cancer (CRC) that is metastatic.
- Eligible to receive cetuximab per Chinese approved label with regard to tumor Rat Sarcoma Viral Oncogene Homologue (RAS) mutation status (i.e. approved for Rat Sarcoma Viral Oncogene Homologue Wild Type(RAS wt) status).
- Able to provide a sufficient amount of representative tumor specimen for central prospective laboratory testing of B-RAF Proto-oncogene, Serine/threonine Kinase (BRAF) mutation status and also retrospective RAS wt status and Microsatellite Instability (MSI) testing.
Inclusion Criteria for Treatment Period:
The following inclusion criteria must be met for a participant to be eligible for this study:
- Chinese male or female participant with age ≥18 years at time of informed consent.
- Histologically or cytologically confirmed CRC that is metastatic and unresectable at time of study entry (i.e. not suitable for complete surgical resection at screening).
- Presence of a BRAF V600E mutation in tumor tissue previously determined by a local assay at any time before screening or by the central laboratory.
NOTE: Other protocol defined Inclusion criteria may apply
Exclusion Criteria for Molecular Prescreening:
Participants meeting any of the following criteria are not eligible to undergo molecular tumor prescreening:
- Prior anti-Epidermal Growth Factor Receptor (anti-EGFR) treatment
- More than two prior regimens in the metastatic setting.
- Known contraindication to receive cetuximab or irinotecan at the planned dose according to the most recent cetuximab and irinotecan local label.
- Known history of Gilbert's syndrome or is known to have any of the following genotypes: uridine 5'-diphospho-glucuronosyltransferase (UGT)1A1*6/*6, UGT1A1*28/*28 or UGT1A1*6/*28.
- Leptomeningeal disease.
Exclusion Criteria for Treatment Period:
- Prior treatment with any Proto oncogene Serine/threonine-Protein Kinase (RAF) inhibitor, cetuximab, panitumumab or other EGFR inhibitors.
- Symptomatic brain metastasis.
- Leptomeningeal disease.
- Use of any herbal medications/supplements or any medications or foods that are moderate or strong inhibitors or inducers of cytochrome P450 (CYP)3A4/5 ≤1 week before the start of study intervention.
- Known history of acute or chronic pancreatitis within 6 months before the start of study intervention.
NOTE: Other protocol defined Exclusion criteria may apply
Data sourced from ClinicalTrials.gov (NCT05004350). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.