Trial Outcomes & Findings for Encorafenib, Binimetinib and Cetuximab in Subjects With Previously Untreated BRAF-mutant ColoRectal Cancer (NCT NCT03693170)

Last Updated: 2024-02-02

Results Overview

The confirmed overall response rate (cORR) is the percentage of confirmed responses, defined as complete response (CR) or partial response (PR), as assessed by local radiologist/investigator review based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions; Partiel response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

95 participants

Primary outcome timeframe

From initiation of treatment to disease progression up to a maximum of 17.6 months.

Results posted on

2024-02-02

Participant Flow

95 subjects were enrolled in the study between 17 January 2019 and 27 December 2019 in 68 investigational centers : 45 in EU, 7 in UK, 10 in USA and 6 in Japan

125 subjects were screened for inclusion in the study. 30 subjects were excluded (29 due to eligibility criteria not met and 1 due to adverse event).

Participant milestones

Participant milestones
Measure	Encorafenib Plus Binimetinib Plus Cetuximab Encorafenib: 300 mg QD. Binimetinib: 45 mg PO BID. Cetuximab: 400 mg/m2 intravenous (IV) at Cycle 1 day 1 then 250 mg/m2 (IV) every week (QW) for the first 28 weeks. Then, 500mg/m2 IV every two weeks (Q2W) from week 29 (Cycle 8 day 1)
Overall Study STARTED	95
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	75

Reasons for withdrawal

Reasons for withdrawal
Measure	Encorafenib Plus Binimetinib Plus Cetuximab Encorafenib: 300 mg QD. Binimetinib: 45 mg PO BID. Cetuximab: 400 mg/m2 intravenous (IV) at Cycle 1 day 1 then 250 mg/m2 (IV) every week (QW) for the first 28 weeks. Then, 500mg/m2 IV every two weeks (Q2W) from week 29 (Cycle 8 day 1)
Overall Study Disease Progression	48
Overall Study Adverse Event	16
Overall Study Physician Decision	6
Overall Study Protocol Violation	2
Overall Study Death	1
Overall Study Non compliance with study drug	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Encorafenib, Binimetinib and Cetuximab in Subjects With Previously Untreated BRAF-mutant ColoRectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1 Arm n=95 Participants encorafenib plus binimetinib plus cetuximab encorafenib: Once daily, orally Binimetinib: Twice daily, orally Cetuximab: Standard of care for the 28 first weeks and then every 2 weeks
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	43 Participants n=5 Participants
Age, Categorical >=65 years	52 Participants n=5 Participants
Age, Continuous	65 years n=5 Participants
Sex: Female, Male Female	51 Participants n=5 Participants
Sex: Female, Male Male	44 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	73 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	14 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	11 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	71 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	13 Participants n=5 Participants
Region of Enrollment Austria	1 Participants n=5 Participants
Region of Enrollment Netherlands	1 Participants n=5 Participants
Region of Enrollment Belgium	9 Participants n=5 Participants
Region of Enrollment United States	3 Participants n=5 Participants
Region of Enrollment Japan	11 Participants n=5 Participants
Region of Enrollment Italy	15 Participants n=5 Participants
Region of Enrollment United Kingdom	13 Participants n=5 Participants
Region of Enrollment France	13 Participants n=5 Participants
Region of Enrollment Spain	29 Participants n=5 Participants
Primary tumor location Right-sided/transverse	57 Participants n=5 Participants
Primary tumor location Left-sided/rectum	37 Participants n=5 Participants
Primary tumor location Other	1 Participants n=5 Participants
Number of metastatic organs 1	23 Participants n=5 Participants
Number of metastatic organs 2	33 Participants n=5 Participants
Number of metastatic organs >2	39 Participants n=5 Participants
ECOG Performance Status 0	43 Participants n=5 Participants
ECOG Performance Status 1	52 Participants n=5 Participants
Local BRAFV600E mutation result Positive	95 Participants n=5 Participants
Local BRAFV600E mutation result Negative	0 Participants n=5 Participants
Central BRAFV600E mutation result Positive	92 Participants n=5 Participants
Central BRAFV600E mutation result Negative	2 Participants n=5 Participants
Central BRAFV600E mutation result Indeterminate	1 Participants n=5 Participants
Metastatic organs Adrenal gland	3 Participants n=5 Participants
Metastatic organs Bone	4 Participants n=5 Participants
Metastatic organs Liver	52 Participants n=5 Participants
Metastatic organs Lung	35 Participants n=5 Participants
Metastatic organs Lymph node	49 Participants n=5 Participants
Metastatic organs Mediastinum	4 Participants n=5 Participants
Metastatic organs Ovary	3 Participants n=5 Participants
Metastatic organs Peritoneum/Omentum	46 Participants n=5 Participants
Metastatic organs Pleural cavity	3 Participants n=5 Participants
Metastatic organs Rectum	1 Participants n=5 Participants
Metastatic organs Skin	1 Participants n=5 Participants
Metastatic organs Stomach	2 Participants n=5 Participants
Metastatic organs Other	11 Participants n=5 Participants
Prior antineoplastic therapy setting Adjuvant	17 Participants n=5 Participants
Prior antineoplastic therapy setting Neo-adjuvant	3 Participants n=5 Participants
Prior antineoplastic therapy setting Locally advanced	2 Participants n=5 Participants
Prior antineoplastic monotherapy / combination 5-Fluorouracil + Folinic Acid	4 Participants n=5 Participants
Prior antineoplastic monotherapy / combination 5-Fluorouracil + Folinic Acid + Oxaliplatin	9 Participants n=5 Participants
Prior antineoplastic monotherapy / combination Oxaliplatin + Capecitabine	5 Participants n=5 Participants
Prior antineoplastic monotherapy / combination Capecitabine	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: From initiation of treatment to disease progression up to a maximum of 17.6 months.

Population: The Efficacy Set (ES) is composed of all included subjects having received at least one dose of study treatment (partial or full) with a centrally confirmed BRAFV600E mutation.

Outcome measures

Outcome measures
Measure	1 Arm n=92 Participants encorafenib plus binimetinib plus cetuximab encorafenib: Once daily, orally Binimetinib: Twice daily, orally Cetuximab: Standard of care for the 28 first weeks and then every 2 weeks
Confirmed Overall Response Rate (cORR) Based on Local Tumor Assessments	47.8 percentage of confirmed responses Interval 37.3 to 58.5

SECONDARY outcome

Timeframe: From initiation of treatment to disease progression up to a maximum of 17.6 months

Population: The Efficacy Set (ES) is composed of all included subjects having received at least one dose of study treatment (partial or full) with a centrally confirmed BRAFV600E mutation.

The confirmed overall response rate (cORR) is the percentage of confirmed responses, defined as complete response (CR) or partial response (PR), as assessed by central radiologist review based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions; Partiel response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	1 Arm n=92 Participants encorafenib plus binimetinib plus cetuximab encorafenib: Once daily, orally Binimetinib: Twice daily, orally Cetuximab: Standard of care for the 28 first weeks and then every 2 weeks
Confirmed Overall Response Rate (cORR) Based on Central Tumor Assessment	45.7 percentage of confirmed responses Interval 35.2 to 56.4

SECONDARY outcome

Timeframe: From initiation of treatment to disease progression up to a maximum of 17.6 months

Population: The Efficacy Set (ES) is composed of all included subjects having received at least one dose of study treatment (partial or full) with a centrally confirmed BRAFV600E mutation.

The overall response rate (ORR) is the percentage of responses, defined as complete response (CR) or partial response (PR), as assessed by local radiologist/investigator review based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions; Partiel response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	1 Arm n=92 Participants encorafenib plus binimetinib plus cetuximab encorafenib: Once daily, orally Binimetinib: Twice daily, orally Cetuximab: Standard of care for the 28 first weeks and then every 2 weeks
Overall Response Rate (ORR) Based on Local Tumor Assessments	62 percentage of responses Interval 51.2 to 71.9

SECONDARY outcome

Timeframe: From initiation of treatment to disease progression up to a maximum of 17.6 months

Population: The Efficacy Set (ES) is composed of all included subjects having received at least one dose of study treatment (partial or full) with a centrally confirmed BRAFV600E mutation.

The overall response rate (ORR) is the percentage of responses, defined as complete response (CR) or partial response (PR), as assessed by central radiologist review based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions; Partiel response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	1 Arm n=92 Participants encorafenib plus binimetinib plus cetuximab encorafenib: Once daily, orally Binimetinib: Twice daily, orally Cetuximab: Standard of care for the 28 first weeks and then every 2 weeks
Overall Response Rate (ORR) Based on Central Tumor Assessments	60.9 percentage of responses Interval 50.1 to 70.9

SECONDARY outcome

Timeframe: From first radiographic evidence of response to disease progression up to a maximum of 17.6 months

Population: Confirmed responders per local radiologist/investigator assessment

Time from first radiographic evidence of response based on local radiologist/investigator review to the earliest documented PD or death due to underlying disease

Outcome measures

Outcome measures
Measure	1 Arm n=45 Participants encorafenib plus binimetinib plus cetuximab encorafenib: Once daily, orally Binimetinib: Twice daily, orally Cetuximab: Standard of care for the 28 first weeks and then every 2 weeks
Duration of Response (DOR) Per Local Assessment	5.1 months Interval 3.7 to 6.9

SECONDARY outcome

Timeframe: From first radiographic evidence of response to disease progression up to a maximum of 17.6 months

Population: Confirmed responders per central assessment

Time from first radiographic evidence of response based on central review to the earliest documented PD or death due to underlying disease

Outcome measures

Outcome measures
Measure	1 Arm n=42 Participants encorafenib plus binimetinib plus cetuximab encorafenib: Once daily, orally Binimetinib: Twice daily, orally Cetuximab: Standard of care for the 28 first weeks and then every 2 weeks
Duration of Response (DOR) Per Central Assessment	5.1 months Interval 3.4 to 5.5

SECONDARY outcome

Timeframe: From initiation of treatment to the first radiographic evidence of response up to a maximum of 17.6 months

Population: Confirmed responders per local radiologist/investigator assessment

The TTR is defined as the time from the first dose until the first documented radiographic evidence of response of CR or PR per local review

Outcome measures

Outcome measures
Measure	1 Arm n=45 Participants encorafenib plus binimetinib plus cetuximab encorafenib: Once daily, orally Binimetinib: Twice daily, orally Cetuximab: Standard of care for the 28 first weeks and then every 2 weeks
Time to Response (TTR) Per Local Review	1.4 months Interval 1.4 to 1.5

SECONDARY outcome

Timeframe: From initiation of treatment to the first radiographic evidence of response up to a maximum of 17.6 months

Population: Confirmed responders per central assessment

The TTR is defined as the time from the first dose until the first documented radiographic evidence of response of CR or PR per central review

Outcome measures

Outcome measures
Measure	1 Arm n=42 Participants encorafenib plus binimetinib plus cetuximab encorafenib: Once daily, orally Binimetinib: Twice daily, orally Cetuximab: Standard of care for the 28 first weeks and then every 2 weeks
Time to Response (TTR) Per Central Review	1.4 months Interval 1.3 to 1.4

SECONDARY outcome

Timeframe: From initiation of treatment to disease progression or death up to a maximum of 17.6 months

Population: The Efficacy Set (ES) is composed of all included subjects having received at least one dose of study treatment (partial or full) with a centrally confirmed BRAFV600E mutation.

Time from first dose to the earliest documented date of disease progression based on local radiologist/investigator review or death due to any cause

Outcome measures

Outcome measures
Measure	1 Arm n=92 Participants encorafenib plus binimetinib plus cetuximab encorafenib: Once daily, orally Binimetinib: Twice daily, orally Cetuximab: Standard of care for the 28 first weeks and then every 2 weeks
Progression-Free Survival (PFS) Per Local Review	5.8 months Interval 4.6 to 6.4

SECONDARY outcome

Timeframe: From initiation of treatment to disease progression or death up to a maximum of 17.6 months

Population: The Efficacy Set (ES) is composed of all included subjects having received at least one dose of study treatment (partial or full) with a centrally confirmed BRAFV600E mutation.

Time from first dose to the earliest documented date of disease progression based on central review or death due to any cause

Outcome measures

Outcome measures
Measure	1 Arm n=92 Participants encorafenib plus binimetinib plus cetuximab encorafenib: Once daily, orally Binimetinib: Twice daily, orally Cetuximab: Standard of care for the 28 first weeks and then every 2 weeks
Progression of Free Survival (PFS) Per Central Review	5.0 months Interval 4.6 to 6.4

SECONDARY outcome

Timeframe: From initiation of treatment to death up to a maximum of 17.6 months

Population: The Full Analysis Set (FAS) is composed of all subjects having received at least one dose of study treatment (partial or full)

Time from first dose to death due to any cause

Outcome measures

Outcome measures
Measure	1 Arm n=95 Participants encorafenib plus binimetinib plus cetuximab encorafenib: Once daily, orally Binimetinib: Twice daily, orally Cetuximab: Standard of care for the 28 first weeks and then every 2 weeks
Overall Survival (OS)	17.2 months Interval 14.1 to Insufficient data maturity

SECONDARY outcome

Timeframe: 2 hours and 6 hours after dose on Day 1 cycle 1; Predose and 2 hours post dose on Day 1 cycle 2 (cycle length = 28 days)

Plasma concentration of encorafenib

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 hours and 6 hours after dose on Day 1 cycle 1; Predose and 2 hours post dose on Day 1 cycle 2 (cycle length = 28 days)

Plasma concentration of binimetinib

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 hours and 6 hours after dose on Day 1 cycle 1; Predose and 2 hours post dose on Day 1 cycle 2 (cycle length = 28 days)

Plasma concentration of cetuximab

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From Cycle 1 Day 1 (C1D1) Visit to the 30-day Safety Follow-up Visit up to a maximum of 17.6 months

Population: Changes from baseline are shown up to Cycle 10 Day 1 (C10D1) and for the 30-day safety follow-up period. Beyond C10D1, less than 10 subjects filled the questionnaire. Participants analyzed corresponds to the number of participant who completed the questionnaire the at the respective time point.

The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for cancer subjects (EORTC QLQ-C30) includes a global health status/QoL. The scale ranges in score from 0 to 100, higher score on the global health status/QoL scale indicate higher QoL. Changes from baseline in EORTC QLQ-C30 global health status/quality of life (QoL) over time are presented in this record.

Outcome measures

Outcome measures
Measure	1 Arm n=95 Participants encorafenib plus binimetinib plus cetuximab encorafenib: Once daily, orally Binimetinib: Twice daily, orally Cetuximab: Standard of care for the 28 first weeks and then every 2 weeks
Change From Baseline in EORTC QLQ-C30 Over Time C2D1	-2.64 units on a scale Standard Deviation 19.270
Change From Baseline in EORTC QLQ-C30 Over Time C3D1	-0.35 units on a scale Standard Deviation 20.866
Change From Baseline in EORTC QLQ-C30 Over Time C4D1	0.97 units on a scale Standard Deviation 20.238
Change From Baseline in EORTC QLQ-C30 Over Time C5D1	-0.89 units on a scale Standard Deviation 18.026
Change From Baseline in EORTC QLQ-C30 Over Time C6D1	-1.92 units on a scale Standard Deviation 22.544
Change From Baseline in EORTC QLQ-C30 Over Time C7D1	-5.39 units on a scale Standard Deviation 22.834
Change From Baseline in EORTC QLQ-C30 Over Time C8D1	-4.63 units on a scale Standard Deviation 21.225
Change From Baseline in EORTC QLQ-C30 Over Time C9D1	-1.85 units on a scale Standard Deviation 15.274
Change From Baseline in EORTC QLQ-C30 Over Time C10D1	-7.69 units on a scale Standard Deviation 17.167
Change From Baseline in EORTC QLQ-C30 Over Time 30 days safety Follow up	-15.42 units on a scale Standard Deviation 25.775

SECONDARY outcome

Timeframe: From Cycle 1 Day 1 (C1D1) Visit to the 30-day Safety Follow-up Visit up to a maximum of 17.6 months

The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L VAS records the patient's self-rated health on a vertical visual analogue scale numbered from 0 ("The worst health you can imagine") to 100 ("The best health you can imagine"). Changes from baseline in EQ-5D-5L VAS over time are presented in this record.

Outcome measures

Outcome measures
Measure	1 Arm n=95 Participants encorafenib plus binimetinib plus cetuximab encorafenib: Once daily, orally Binimetinib: Twice daily, orally Cetuximab: Standard of care for the 28 first weeks and then every 2 weeks
Change From Baseline in EQ-5D-5L Over Time C2D1	0.04 units on a scale Standard Deviation 19.707
Change From Baseline in EQ-5D-5L Over Time C3D1	0.35 units on a scale Standard Deviation 21.668
Change From Baseline in EQ-5D-5L Over Time C4D1	2.66 units on a scale Standard Deviation 19.400
Change From Baseline in EQ-5D-5L Over Time C5D1	3.73 units on a scale Standard Deviation 17.052
Change From Baseline in EQ-5D-5L Over Time C6D1	1.69 units on a scale Standard Deviation 18.421
Change From Baseline in EQ-5D-5L Over Time C7D1	1.31 units on a scale Standard Deviation 18.903
Change From Baseline in EQ-5D-5L Over Time C8D1	2.89 units on a scale Standard Deviation 15.882
Change From Baseline in EQ-5D-5L Over Time C9D1	-2.32 units on a scale Standard Deviation 21.945
Change From Baseline in EQ-5D-5L Over Time C10D1	-4.00 units on a scale Standard Deviation 12.503
Change From Baseline in EQ-5D-5L Over Time 30 days safety Follow up	-9.35 units on a scale Standard Deviation 23.585

SECONDARY outcome

Timeframe: From Cycle 1 Day 1 (C1D1) Visit to the 30-day Safety Follow-up Visit up to a maximum of 17.6 months

Population: PGIC scores are shown up to Cycle 10 Day 1 (C10D1) and for the 30-day safety follow-up period. Beyond C10D1, less than 10 subjects filled the questionnaire. Participants analyzed corresponds to the number of participant who completed the questionnaire the at the respective time point.

The Patient Global Impression of Change (PGIC) is a measure of patients' perceptions of change in their symptoms over time. For this assessment, subjects answered the following question: "Since starting treatment, my colorectal cancer symptoms are: (1) very much improved, (2) much improved, (3) minimally improved, (4) no change, (5) minimally worse, (6) much worse or (7) very much worse."

Outcome measures

Outcome measures
Measure	1 Arm n=95 Participants encorafenib plus binimetinib plus cetuximab encorafenib: Once daily, orally Binimetinib: Twice daily, orally Cetuximab: Standard of care for the 28 first weeks and then every 2 weeks
PGIC Scores Over Time C2D1 · Very much improved	5 Participants
PGIC Scores Over Time C2D1 · Much improved	15 Participants
PGIC Scores Over Time C2D1 · Minimally improved	17 Participants
PGIC Scores Over Time C2D1 · No change	29 Participants
PGIC Scores Over Time C2D1 · Minimally worse	3 Participants
PGIC Scores Over Time C2D1 · Much worse	0 Participants
PGIC Scores Over Time C2D1 · Very much worse	0 Participants
PGIC Scores Over Time C2D1 · Missing, not done	22 Participants
PGIC Scores Over Time C3D1 · Very much improved	10 Participants
PGIC Scores Over Time C3D1 · Much improved	28 Participants
PGIC Scores Over Time C3D1 · Minimally improved	11 Participants
PGIC Scores Over Time C3D1 · No change	20 Participants
PGIC Scores Over Time C6D1 · Minimally worse	0 Participants
PGIC Scores Over Time C6D1 · Much worse	0 Participants
PGIC Scores Over Time C6D1 · Very much worse	0 Participants
PGIC Scores Over Time C6D1 · Missing, not done	6 Participants
PGIC Scores Over Time C7D1 · Very much improved	4 Participants
PGIC Scores Over Time C7D1 · Much improved	13 Participants
PGIC Scores Over Time C7D1 · Minimally improved	7 Participants
PGIC Scores Over Time C7D1 · No change	11 Participants
PGIC Scores Over Time C7D1 · Minimally worse	0 Participants
PGIC Scores Over Time C7D1 · Much worse	0 Participants
PGIC Scores Over Time C7D1 · Very much worse	0 Participants
PGIC Scores Over Time C7D1 · Missing, not done	8 Participants
PGIC Scores Over Time C8D1 · Very much improved	4 Participants
PGIC Scores Over Time C8D1 · Much improved	11 Participants
PGIC Scores Over Time C8D1 · Minimally improved	5 Participants
PGIC Scores Over Time C8D1 · No change	5 Participants
PGIC Scores Over Time C8D1 · Minimally worse	2 Participants
PGIC Scores Over Time C8D1 · Much worse	0 Participants
PGIC Scores Over Time C8D1 · Very much worse	0 Participants
PGIC Scores Over Time C8D1 · Missing, not done	6 Participants
PGIC Scores Over Time C9D1 · Very much improved	1 Participants
PGIC Scores Over Time C9D1 · Much improved	9 Participants
PGIC Scores Over Time C9D1 · Minimally improved	2 Participants
PGIC Scores Over Time C9D1 · No change	5 Participants
PGIC Scores Over Time C9D1 · Minimally worse	0 Participants
PGIC Scores Over Time C9D1 · Much worse	0 Participants
PGIC Scores Over Time C9D1 · Very much worse	0 Participants
PGIC Scores Over Time C9D1 · Missing, not done	3 Participants
PGIC Scores Over Time C10D1 · Very much improved	2 Participants
PGIC Scores Over Time C10D1 · Much improved	4 Participants
PGIC Scores Over Time C10D1 · Minimally improved	4 Participants
PGIC Scores Over Time C10D1 · No change	4 Participants
PGIC Scores Over Time C10D1 · Minimally worse	0 Participants
PGIC Scores Over Time C10D1 · Much worse	0 Participants
PGIC Scores Over Time C10D1 · Very much worse	0 Participants
PGIC Scores Over Time C10D1 · Missing, not done	0 Participants
PGIC Scores Over Time 30 days safety Follow-up · Very much improved	3 Participants
PGIC Scores Over Time 30 days safety Follow-up · Much improved	12 Participants
PGIC Scores Over Time 30 days safety Follow-up · Minimally improved	5 Participants
PGIC Scores Over Time 30 days safety Follow-up · No change	9 Participants
PGIC Scores Over Time 30 days safety Follow-up · Minimally worse	6 Participants
PGIC Scores Over Time 30 days safety Follow-up · Much worse	6 Participants
PGIC Scores Over Time 30 days safety Follow-up · Very much worse	0 Participants
PGIC Scores Over Time 30 days safety Follow-up · Missing, not done	31 Participants
PGIC Scores Over Time C3D1 · Minimally worse	0 Participants
PGIC Scores Over Time C3D1 · Much worse	0 Participants
PGIC Scores Over Time C3D1 · Very much worse	0 Participants
PGIC Scores Over Time C3D1 · Missing, not done	12 Participants
PGIC Scores Over Time C4D1 · Very much improved	9 Participants
PGIC Scores Over Time C4D1 · Much improved	31 Participants
PGIC Scores Over Time C4D1 · Minimally improved	12 Participants
PGIC Scores Over Time C4D1 · No change	16 Participants
PGIC Scores Over Time C4D1 · Minimally worse	0 Participants
PGIC Scores Over Time C4D1 · Much worse	0 Participants
PGIC Scores Over Time C4D1 · Very much worse	0 Participants
PGIC Scores Over Time C4D1 · Missing, not done	9 Participants
PGIC Scores Over Time C5D1 · Very much improved	10 Participants
PGIC Scores Over Time C5D1 · Much improved	19 Participants
PGIC Scores Over Time C5D1 · Minimally improved	11 Participants
PGIC Scores Over Time C5D1 · No change	13 Participants
PGIC Scores Over Time C5D1 · Minimally worse	2 Participants
PGIC Scores Over Time C5D1 · Much worse	0 Participants
PGIC Scores Over Time C5D1 · Very much worse	0 Participants
PGIC Scores Over Time C5D1 · Missing, not done	10 Participants
PGIC Scores Over Time C6D1 · Very much improved	7 Participants
PGIC Scores Over Time C6D1 · Much improved	18 Participants
PGIC Scores Over Time C6D1 · Minimally improved	13 Participants
PGIC Scores Over Time C6D1 · No change	13 Participants

Adverse Events

1 Arm

Serious events: 49 serious events

Other events: 93 other events

Deaths: 27 deaths

Serious adverse events

Serious adverse events
Measure	1 Arm n=95 participants at risk encorafenib plus binimetinib plus cetuximab encorafenib: Once daily, orally Binimetinib: Twice daily, orally Cetuximab: Standard of care for the 28 first weeks and then every 2 weeks
Blood and lymphatic system disorders Anaemia	2.1% 2/95 • Number of events 2 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Cardiac disorders Cardiac failure	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Cardiac disorders Myocardial infarction	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Cardiac disorders Myocarditis	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Eye disorders Detachment of retinal pigment epithelium	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Abdominal pain	4.2% 4/95 • Number of events 4 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Abdominal pain upper	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Diarrhoea	4.2% 4/95 • Number of events 4 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Diverticulum	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Enteritis	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Enterocolitis	1.1% 1/95 • Number of events 2 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Intestinal obstruction	5.3% 5/95 • Number of events 5 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Intra-abdominal fluid collection	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Large intestinal obstruction	6.3% 6/95 • Number of events 6 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Large intestine perforation	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Nausea	5.3% 5/95 • Number of events 5 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Pancreatitis acute	1.1% 1/95 • Number of events 2 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Small intestinal obstruction	4.2% 4/95 • Number of events 5 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Subileus	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Vomiting	4.2% 4/95 • Number of events 4 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
General disorders Asthenia	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
General disorders General physical health deterioration	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
General disorders Pyrexia	2.1% 2/95 • Number of events 2 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Hepatobiliary disorders Bile duct stenosis	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Hepatobiliary disorders Cholangitis	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Hepatobiliary disorders Cholecystitis	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Hepatobiliary disorders Hepatic function abnormal	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Infections and infestations Appendicitis	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Infections and infestations Bacteraemia	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Infections and infestations Biliary tract infection	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Infections and infestations Cellulitis	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Infections and infestations Escherichia sepsis	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Infections and infestations Lymph node tuberculosis	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Infections and infestations Respiratory tract infection	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Infections and infestations Sepsis	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Infections and infestations Streptococcal bacteraemia	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Infections and infestations Tuberculosis	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Infections and infestations Urinary tract infection	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Injury, poisoning and procedural complications Diversion colitis	1.1% 1/95 • Number of events 3 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Injury, poisoning and procedural complications Femoral neck fracture	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Injury, poisoning and procedural complications Infusion related reaction	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Injury, poisoning and procedural complications Lumbar vertebral fracture	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Investigations Alanine aminotransferase increased	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Investigations Aspartate aminotransferase increased	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Investigations Blood bilirubin increased	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Investigations Blood creatine phosphokinase increased	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Investigations Gamma-glutamyltransferase increased	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Metabolism and nutrition disorders Decreased appetite	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Metabolism and nutrition disorders Hypokalaemia	1.1% 1/95 • Number of events 2 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Musculoskeletal and connective tissue disorders Back pain	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour associated fever	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Nervous system disorders Dizziness	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Renal and urinary disorders Acute kidney injury	6.3% 6/95 • Number of events 8 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Renal and urinary disorders Haematuria	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Renal and urinary disorders Nephritis	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Renal and urinary disorders Nephrolithiasis	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Renal and urinary disorders Renal failure	2.1% 2/95 • Number of events 2 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.1% 1/95 • Number of events 1 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.

Other adverse events

Other adverse events
Measure	1 Arm n=95 participants at risk encorafenib plus binimetinib plus cetuximab encorafenib: Once daily, orally Binimetinib: Twice daily, orally Cetuximab: Standard of care for the 28 first weeks and then every 2 weeks
Gastrointestinal disorders Abdominal discomfort	6.3% 6/95 • Number of events 6 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Abdominal pain	32.6% 31/95 • Number of events 43 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Abdominal pain upper	7.4% 7/95 • Number of events 11 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Investigations Amylase increased	10.5% 10/95 • Number of events 17 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Blood and lymphatic system disorders Anaemia	24.2% 23/95 • Number of events 60 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Musculoskeletal and connective tissue disorders Arthralgia	8.4% 8/95 • Number of events 14 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
General disorders Asthenia	31.6% 30/95 • Number of events 67 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Musculoskeletal and connective tissue disorders Back pain	9.5% 9/95 • Number of events 9 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Investigations Blood creatine phosphokinase increased	5.3% 5/95 • Number of events 7 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Investigations Blood creatinine increased	9.5% 9/95 • Number of events 11 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Constipation	26.3% 25/95 • Number of events 26 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Respiratory, thoracic and mediastinal disorders Cough	8.4% 8/95 • Number of events 9 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Metabolism and nutrition disorders Decreased appetite	23.2% 22/95 • Number of events 36 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Skin and subcutaneous tissue disorders Dermatitis acneiform	40.0% 38/95 • Number of events 77 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Diarrhoea	67.4% 64/95 • Number of events 145 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Skin and subcutaneous tissue disorders Dry skin	31.6% 30/95 • Number of events 35 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Nervous system disorders Dysgeusia	12.6% 12/95 • Number of events 13 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Dyspepsia	8.4% 8/95 • Number of events 8 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Respiratory, thoracic and mediastinal disorders Dysphonia	6.3% 6/95 • Number of events 8 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Respiratory, thoracic and mediastinal disorders Dyspnoea	15.8% 15/95 • Number of events 23 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Skin and subcutaneous tissue disorders Erythema	5.3% 5/95 • Number of events 5 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
General disorders Fatigue	18.9% 18/95 • Number of events 38 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Flatulence	5.3% 5/95 • Number of events 5 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Nervous system disorders Headache	10.5% 10/95 • Number of events 11 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Metabolism and nutrition disorders Hyperkalaemia	5.3% 5/95 • Number of events 6 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Skin and subcutaneous tissue disorders Hypertrichosis	6.3% 6/95 • Number of events 6 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Metabolism and nutrition disorders Hypoalbuminaemia	7.4% 7/95 • Number of events 13 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Metabolism and nutrition disorders Hypomagnesaemia	6.3% 6/95 • Number of events 9 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Psychiatric disorders Insomnia	5.3% 5/95 • Number of events 6 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Investigations Lipase increased	12.6% 12/95 • Number of events 24 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
General disorders Mucosal inflammation	6.3% 6/95 • Number of events 6 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Musculoskeletal and connective tissue disorders Muscle spasms	5.3% 5/95 • Number of events 5 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Musculoskeletal and connective tissue disorders Myalgia	6.3% 6/95 • Number of events 8 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Nausea	44.2% 42/95 • Number of events 83 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	5.3% 5/95 • Number of events 6 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Infections and infestations Paronychia	11.6% 11/95 • Number of events 11 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Skin and subcutaneous tissue disorders Pruritus	12.6% 12/95 • Number of events 16 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
General disorders Pyrexia	12.6% 12/95 • Number of events 19 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Skin and subcutaneous tissue disorders Rash	40.0% 38/95 • Number of events 56 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Rectal haemorrhage	6.3% 6/95 • Number of events 8 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Skin and subcutaneous tissue disorders Skin fissures	11.6% 11/95 • Number of events 17 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Stomatitis	8.4% 8/95 • Number of events 16 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Eye disorders Vision blurred	13.7% 13/95 • Number of events 17 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Gastrointestinal disorders Vomiting	35.8% 34/95 • Number of events 59 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.
Investigations Weight decreased	6.3% 6/95 • Number of events 8 • From patient enrolment date to 30 days after the last dose of study drug up to a maximum of 17.6 months Only treatment emergent Adverse Events are provided in summary tables. A treatment emergent adverse event (TEAE) is defined as any event that first occurred during the treatment period (i.e. from first treatment administration date up to last administration date + 30 days) or that worsened during that study period.

Additional Information

Isabelle Klauck, MD

Pierre Fabre Medicament

Phone: +33149108018

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60