Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer (BEACON CRC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT02928224

Recruitment Status : Active, not recruiting

First Posted : October 10, 2016

Results First Posted : July 14, 2020

Last Update Posted : February 17, 2021

Sponsor:

Collaborators:

Merck KGaA, Darmstadt, Germany

Pierre Fabre Medicament

Ono Pharmaceutical Co. Ltd

Information provided by (Responsible Party):

Pfizer

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	BRAF V600E-mutant Metastatic Colorectal Cancer
Interventions	Drug: Encorafenib Drug: Binimetinib Drug: Cetuximab Drug: Irinotecan Drug: Folinic Acid Drug: 5-Fluorouracil
Enrollment	702

Participant Flow

Recruitment Details	Patients were at least 18 years of age with confirmed metastatic colorectal cancer (CRC) whose disease had progressed after 1 or 2 prior regimens in the metastatic setting and whose tumor tissue was BRAF V600E-mutant as previously determined by a local assay at any time prior to Screening
Pre-assignment Details


Arm/Group Title	Combined Safety Lead-in	Phase 3: Triplet Arm	Phase 3: Doublet Arm	Phase 3:Control Arm
Arm/Group Description	Encorafenib + binimetinib + cetuxim...	Encorafenib + binimetinib + cetuxim...	Encorafenib + cetuximab. ...	Investigator's choice of either iri...
Arm/Group Description	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Period Title: Overall Study
Started	37	224	220	221
Completed	0	0	0	0
Not Completed	37	224	220	221
Reason Not Completed
Randomized, Not Treated	0	2	4	28
Treatment Ongoing	6	78	78	37
Progressive Disease	23	104	101	103
Adverse Event	2	11	11	10
Changes in Patient's Condition	3	9	9	13
Death	1	7	5	11
Withdrawal by Subject	1	4	3	9
Dose Interruptions>28	1	2	2	4
Patient Decision to Discontinue Drug	0	2	2	4
Physician Decision	0	2	4	2
not listed	0	3	1	0

Baseline Characteristics

Arm/Group Title		Combined Safety Lead-in (CSLI)	Phase 3: Triplet Arm	Phase 3: Doublet Arm	Phase 3:Control Arm	Total
Arm/Group Description		Encorafenib + binimetinib + cetuxim...	Encorafenib + binimetinib + cetuxim...	Encorafenib + cetuximab. ...	Investigator's choice of either iri...	Total of all reporting groups
Arm/Group Description		Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.	Total of all reporting groups
Overall Number of Baseline Participants		37	224	220	221	702
Baseline Analysis Population Description		...
Baseline Analysis Population Description		The baseline analysis population consists of the Full Analysis Set (FAS). For patients in the CSLI, the FAS includes all patients who received at least 1 dose of study drug and had at least 1 post treatment assessment, which may include death. For the randomized Phase 3 portion of the study, the FAS consists of all randomized patients.
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	37 participants	224 participants	220 participants	221 participants	702 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	23 62.2%	141 62.9%	137 62.3%	149 67.4%	450 64.1%
	>=65 years	14 37.8%	83 37.1%	83 37.7%	72 32.6%	252 35.9%
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	37 participants	224 participants	220 participants	221 participants	702 participants
		58.3 (10.34)	59.5 (11.65)	60.2 (11.65)	58.4 (12.07)	59.3 (61)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	37 participants	224 participants	220 participants	221 participants	702 participants
	Female	22 59.5%	119 53.1%	105 47.7%	127 57.5%	373 53.1%
	Male	15 40.5%	105 46.9%	115 52.3%	94 42.5%	329 46.9%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	37 participants	224 participants	220 participants	221 participants	702 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	7 18.9%	20 8.9%	25 11.4%	39 17.6%	91 13.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	1 2.7%	2 0.9%	0 0.0%	0 0.0%	3 0.4%
	White	29 78.4%	195 87.1%	183 83.2%	172 77.8%	579 82.5%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	7 3.1%	12 5.5%	10 4.5%	29 4.1%
Region Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	37 participants	224 participants	220 participants	221 participants	702 participants
	North America	5 13.5%	30 13.4%	28 12.7%	29 13.1%	92 13.1%
	Europe	25 67.6%	150 67.0%	145 65.9%	125 56.6%	445 63.4%
	Rest of World (includes Mexico)	7 18.9%	44 19.6%	47 21.4%	67 30.3%	165 23.5%
Eastern Cooperative Oncology Group Performance Status (ECOG PS) at Baseline ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	37 participants	224 participants	220 participants	221 participants	702 participants
	0-Fully active	22 59.5%	116 51.8%	112 50.9%	108 48.9%	358 51.0%
	1-Restircted in physically strenuous activity	15 40.5%	108 48.2%	104 47.3%	113 51.1%	340 48.4%
	2-Ambulatory and capable of all self-care	0 0.0%	0 0.0%	4 1.8%	0 0.0%	4 0.6%
		[1] Measure Description: ECOG PS was used to assess the physical health of patients, and ranges from 0 (most active) to 5 (dead). Frequency counts and percentages of patients in each score category were provided by treatment arm and assessment visit.
Primary Tumor Location Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	37 participants	224 participants	220 participants	221 participants	702 participants
	Left Colon	11 29.7%	79 35.3%	83 37.7%	68 30.8%	241 34.3%
	Right Colon	23 62.2%	126 56.3%	110 50.0%	119 53.8%	378 53.8%
	Left and Right Colon	0 0.0%	8 3.6%	11 5.0%	22 10.0%	41 5.8%
	Unknown	3 8.1%	11 4.9%	16 7.3%	12 5.4%	42 6.0%
Primary Tumor Removed Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	37 participants	224 participants	220 participants	221 participants	702 participants
	Completely Resected	20 54.1%	133 59.4%	123 55.9%	122 55.2%	398 56.7%
	Partially Resected/Unresected	17 45.9%	91 40.6%	97 44.1%	99 44.8%	304 43.3%
Number of Organs Involved Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	37 participants	224 participants	220 participants	221 participants	702 participants
	>=2	16 43.2%	114 50.9%	117 53.2%	123 55.7%	370 52.7%
	>=3	21 56.8%	110 49.1%	103 46.8%	98 44.3%	332 47.3%
Sites of Metastases Measure Type: Number Unit of measure: Sites	Number Analyzed	37 participants	224 participants	220 participants	221 participants	702 participants
Liver		24	144	134	128	430
Lung		10	86	83	86	265
Lymph Node		17	86	82	88	273
NodePeritoneum/Omentum		17	77	97	93	284

Outcome Measures

1.Primary Outcome


Title	(Safety Lead-in) Number of Participants With Dose-limiting Toxicities (DLTs)
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Cycle 1 (up to 28 days)

Outcome Measure Data

Analysis Population Description

The Dose-determining Set (DDS) consisted of all CSLI patients from the Safety Set who either completed a minimum exposure requirement (received ≥ 75% dose intensity of the planned dose for each binimetinib, encorafenib and cetuximab) and had sufficient safety evaluations or experienced a dose-limiting toxicity (DLT).


Arm/Group Title	Combined Safety Lead-in (CSLI)
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	37
Measure Type: Count of Participants Unit of Measure: Participants
	5 13.5%

2.Primary Outcome


Title	(Safety Lead-in) Number of Participants With Adverse Events (AEs)
Description	Refer to AE/SAE section for additional data that were measured and ana...
Description	Refer to AE/SAE section for additional data that were measured and analyzed.
Time Frame	Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description

The Safety Set consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. Patients were analyzed according to treatment received.


Arm/Group Title	Combined Safety Lead-in
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	37
Measure Type: Count of Participants Unit of Measure: Participants
	37 100.0%

3.Primary Outcome


Title	(Safety Lead-in) Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to Adverse Events (AEs)
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Combined Safety Lead-in
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	37
Measure Type: Count of Participants Unit of Measure: Participants
	26 70.3%

4.Primary Outcome


Title	(Phase 3) Overall Survival (OS) of Triplet Arm vs. Control Arm
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.


Arm/Group Title	Phase 3: Triplet Arm	Phase 3:Control Arm
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...	Investigator's choice of either iri...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Overall Number of Participants Analyzed	224	221
Median (95% Confidence Interval) Unit of Measure: months
	9.03 (8.02 to 11.43)	5.42 (4.76 to 6.57)

5.Primary Outcome


Title	(Phase 3) Response Rate (ORR) by Blinded Independent Central Review (BICR) Per Response Evaluation Criteria in Solid Tumors (RECIST), v1.1 of Triplet Arm vs. Control Arm
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description

The Phase 3 Response Efficacy Set consisted of the first 330 patients randomized into the Phase 3 portion of the study and any additional patients randomized on the same day as the 330th randomized patient.


Arm/Group Title	Phase 3: Triplet Arm	Phase 3:Control Arm
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...	Investigator's choice of either iri...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Overall Number of Participants Analyzed	111	107
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	29 (18.2 to 35.3)	2 (.2 to 6.6)

6.Secondary Outcome


Title	(Safety Lead-in) Response Rate (ORR) by Investigator
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description

The Safety Lead-in (SLI) Efficacy Set consisted of all CSLI patients in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing).


Arm/Group Title	Combined Safety Lead-in
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	36
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	52.8 (35.5 to 69.6)

7.Secondary Outcome


Title	(Safety Lead-in) Response Rate (ORR) by BICR
Description	ORR per RECIST, v1.1, defined as the number of patients achieving an o...
Description	ORR per RECIST, v1.1, defined as the number of patients achieving an overall best response of CR or partial response (PR) divided by the total number of patients
Time Frame	Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description

The SLI Efficacy Set consisted of all CSLI patients in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing).


Arm/Group Title	Combined Safety Lead-in
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	36
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	41.7 (25.5 to 59.2)

8.Secondary Outcome


Title	(Safety Lead-in) Duration of Response (DOR) by Investigator
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description

The SLI Efficacy Set consisted of all CSLI patients in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing).


Arm/Group Title	Combined Safety Lead-in
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	36
Median (95% Confidence Interval) Unit of Measure: months
	6.47 (4.17 to 11.07)

9.Secondary Outcome


Title	(Safety Lead-in) Duration of Response (DOR) by BICR
Description	DOR defined as the time from first radiographic evidence of response t...
Description	DOR defined as the time from first radiographic evidence of response to the earliest documented disease progression or death due to underlying disease
Time Frame	Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description

The SLI Efficacy Set consisted of all CSLI patients in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing).


Arm/Group Title	Combined Safety Lead-in
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	36
Median (95% Confidence Interval) Unit of Measure: months
	8.15 ^[1] (2.79 to NA)

[1]

NA= not reached. Insufficient number of participants with events to calculate the upper limit of the 95% confidence interval.

10.Secondary Outcome


Title	(Safety Lead-in) Time to Response by Investigator
Description	Time to response defined as the time from first dose to first radiogra...
Description	Time to response defined as the time from first dose to first radiographic evidence of response
Time Frame	Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description

The SLI Efficacy Set consisted of all CSLI patients in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing).


Arm/Group Title	Combined Safety Lead-in
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	36
Median (95% Confidence Interval) Unit of Measure: months
	1.45 (1.38 to 1.64)

11.Secondary Outcome


Title	(Safety Lead-in) Time to Response by BICR
Description	Time to response defined as the time from first dose to first radiogra...
Description	Time to response defined as the time from first dose to first radiographic evidence of response
Time Frame	Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description

The SLI Efficacy Set consisted of all CSLI patients in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing).


Arm/Group Title	Combined Safety Lead-in
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	36
Median (95% Confidence Interval) Unit of Measure: months
	1.45 (1.38 to 1.64)

12.Secondary Outcome


Title	(Safety Lead-in) Progression-free Survival (PFS) by Investigator
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description

The SLI Efficacy Set consisted of all CSLI patients in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing).


Arm/Group Title	Combined Safety Lead-in
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	36
Median (95% Confidence Interval) Unit of Measure: months
	8.08 (5.59 to 9.3)

13.Secondary Outcome


Title	(Safety Lead-in) Progression-free Survival (PFS) by BICR
Description	PFS defined as the time from first dose to the earliest documented dis...
Description	PFS defined as the time from first dose to the earliest documented disease progression or death due to any cause
Time Frame	Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description

The SLI Efficacy Set consisted of all CSLI patients in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing).


Arm/Group Title	Combined Safety Lead-in
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	36
Median (95% Confidence Interval) Unit of Measure: months
	5.59 (4.44 to 9.3)

14.Secondary Outcome


Title	(Phase 3) Overall Survival (OS) in Doublet Arm vs. Control Arm
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.


Arm/Group Title	Phase 3: Doublet Arm	Phase 3:Control Arm
Arm/Group Description:	Encorafenib + cetuximab. ...	Investigator's choice of either iri...
Arm/Group Description:	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Overall Number of Participants Analyzed	220	221
Median (95% Confidence Interval) Unit of Measure: months
	8.41 (7.46 to 11.04)	5.42 (4.76 to 6.57)

15.Secondary Outcome


Title	(Phase 3) Overall Survival (OS) in Triplet Arm vs. Doublet Arm
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.


Arm/Group Title	Phase 3: Triplet Arm	Phase 3: Doublet Arm
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...	Encorafenib + cetuximab. ...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	224	220
Median (95% Confidence Interval) Unit of Measure: months
	9.03 (8.02 to 11.43)	8.41 (7.46 to 11.04)

16.Secondary Outcome


Title	(Phase 3) Comparison of Progression-free Survival (PFS) in Triplet Arm vs Control Arm Per BICR
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 patients.


Arm/Group Title	Phase 3: Triplet Arm	Phase 3:Control Arm
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...	Investigator's choice of either iri...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Overall Number of Participants Analyzed	224	221
Median (95% Confidence Interval) Unit of Measure: months
	4.30 (4.14 to 5.19)	1.51 (1.45 to 1.71)

17.Secondary Outcome


Title	(Phase 3) Comparison of Progression-free Survival (PFS) in Triplet Arm vs Control Arm Per Investigator
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Triplet Arm	Phase 3:Control Arm
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...	Investigator's choice of either iri...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Overall Number of Participants Analyzed	224	221
Median (95% Confidence Interval) Unit of Measure: months
	4.47 (4.24 to 5.36)	1.58 (1.51 to 2.07)

18.Secondary Outcome


Title	(Phase 3) Comparison of Progression-free Survival (PFS) in Doublet Arm vs Control Arm Per BICR
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Doublet Arm	Phase 3:Control Arm
Arm/Group Description:	Encorafenib + cetuximab. ...	Investigator's choice of either iri...
Arm/Group Description:	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Overall Number of Participants Analyzed	220	221
Median (95% Confidence Interval) Unit of Measure: months
	4.21 (3.71 to 5.36)	1.51 (1.45 to 1.71)

19.Secondary Outcome


Title	(Phase 3) Comparison of Progression-free Survival (PFS) in Doublet Arm vs Control Arm Per Investigator
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Doublet Arm	Phase 3:Control Arm
Arm/Group Description:	Encorafenib + cetuximab. ...	Investigator's choice of either iri...
Arm/Group Description:	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Overall Number of Participants Analyzed	220	221
Median (95% Confidence Interval) Unit of Measure: months
	4.27 (4.04 to 5.36)	1.58 (1.51 to 2.07)

20.Secondary Outcome


Title	(Phase 3) Comparison of Progression-free Survival (PFS) in Triplet Arm vs Doublet Arm Per BICR
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Triplet Arm	Phase 3: Doublet Arm
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...	Encorafenib + cetuximab. ...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	224	220
Median (95% Confidence Interval) Unit of Measure: months
	4.30 (4.14 to 5.19)	4.21 (3.71 to 5.36)

21.Secondary Outcome


Title	(Phase 3) Comparison of Progression-free Survival (PFS) in Triplet Arm vs Doublet Arm Per Investigator
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Triplet Arm	Phase 3: Doublet Arm
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...	Encorafenib + cetuximab. ...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	224	220
Median (95% Confidence Interval) Unit of Measure: months
	4.47 (4.24 to 5.36)	4.27 (4.04 to 5.36)

22.Secondary Outcome


Title	Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Control Arm Per Investigator
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Triplet Arm	Phase 3:Control Arm
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...	Investigator's choice of either iri...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Overall Number of Participants Analyzed	224	221
Measure Type: Count of Participants Unit of Measure: Participants
	49 21.9%	7 3.2%

23.Secondary Outcome


Title	(Phase 3) Comparison of Objective Response Rate (ORR) in Doublet Arm vs Control Arm Per BICR
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Doublet Arm	Phase 3:Control Arm
Arm/Group Description:	Encorafenib + cetuximab. ...	Investigator's choice of either iri...
Arm/Group Description:	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Overall Number of Participants Analyzed	113	107
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: participants
	23 (13.4 to 29)	2 (.2 to 6.6)

24.Secondary Outcome


Title	(Phase 3) Comparison of Objective Response Rate (ORR) in Doublet Arm vs Control Arm Per Investigator
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Doublet Arm	Phase 3:Control Arm
Arm/Group Description:	Encorafenib + cetuximab. ...	Investigator's choice of either iri...
Arm/Group Description:	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Overall Number of Participants Analyzed	220	221
Measure Type: Count of Participants Unit of Measure: Participants
	31 14.1%	7 3.2%

25.Secondary Outcome


Title	Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Doublet Arm Per BICR
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Triplet Arm	Phase 3: Doublet Arm
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...	Encorafenib + cetuximab. ...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	111	113
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: participants
	29 (18.2 to 35.3)	23 (13.4 to 29)

26.Secondary Outcome


Title	Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Doublet Arm Per Investigator
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Triplet Arm	Phase 3: Doublet Arm
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...	Encorafenib + cetuximab. ...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	224	220
Measure Type: Count of Participants Unit of Measure: Participants
	49 21.9%	31 14.1%

27.Secondary Outcome


Title	(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Control Arm Per BICR
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Triplet Arm	Phase 3:Control Arm
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...	Investigator's choice of either iri...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Overall Number of Participants Analyzed	111	107
Median (95% Confidence Interval) Unit of Measure: months
	4.80 (2.96 to 9.69)	NA ^[1] (2.56 to NA)

[1]

NA= not reached. Insufficient number of participants with events to calculate the upper limit of the 95% confidence interval.

28.Secondary Outcome


Title	(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Control Arm Per Investigator
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Triplet Arm	Phase 3:Control Arm
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...	Investigator's choice of either iri...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Overall Number of Participants Analyzed	111	107
Median (95% Confidence Interval) Unit of Measure: months
	4.80 (3.29 to 6.57)	5.75 ^[1] (2.56 to NA)

[1]

NA= not reached. Insufficient number of participants with events to calculate the upper limit of the 95% confidence interval.

29.Secondary Outcome


Title	(Phase 3) Comparison of Duration of Response (DOR) in Doublet Arm vs Control Arm Per BICR
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Doublet Arm	Phase 3:Control Arm
Arm/Group Description:	Encorafenib + cetuximab. ...	Investigator's choice of either iri...
Arm/Group Description:	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Overall Number of Participants Analyzed	113	107
Median (95% Confidence Interval) Unit of Measure: months
	6.06 (4.07 to 8.28)	NA ^[1] (2.56 to NA)

[1]

NA= not reached. Insufficient number of participants with events to calculate the upper limit of the 95% confidence interval.

30.Secondary Outcome


Title	(Phase 3) Comparison of Duration of Response (DOR) in Doublet Arm vs Control Arm Per Investigator
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Doublet Arm	Phase 3:Control Arm
Arm/Group Description:	Encorafenib + cetuximab. ...	Investigator's choice of either iri...
Arm/Group Description:	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Overall Number of Participants Analyzed	113	107
Median (95% Confidence Interval) Unit of Measure: months
	5.70 (3.65 to 6.74)	5.75 ^[1] (2.56 to NA)

[1]

NA= not reached. Insufficient number of participants with events to calculate the upper limit of the 95% confidence interval.

31.Secondary Outcome


Title	(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Doublet Arm by BICR
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Triplet Arm	Phase 3:Doublet Arm
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...	Encorafenib + cetuximab. ...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	111	113
Median (95% Confidence Interval) Unit of Measure: months
	4.80 (2.96 to 9.69)	6.06 (4.07 to 8.28)

32.Secondary Outcome


Title	(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Doublet Arm by Investigator
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Triplet Arm	Phase 3:Doublet Arm
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...	Encorafenib + cetuximab. ...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	111	113
Median (95% Confidence Interval) Unit of Measure: months
	4.80 (3.29 to 6.57)	5.70 (3.65 to 6.74)

33.Secondary Outcome


Title	(Phase 3) Comparison of Time to Response in Triplet Arm vs Control Arm Per BICR
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Triplet Arm	Phase 3:Control Arm
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...	Investigator's choice of either iri...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Overall Number of Participants Analyzed	50	3
Median (95% Confidence Interval) Unit of Measure: months
	1.43 (1.41 to 1.51)	1.45 (1.41 to 2.63)

34.Secondary Outcome


Title	(Phase 3) Comparison of Time to Response in Triplet Arm vs Control Arm Per Investigator
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Triplet Arm	Phase 3:Control Arm
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...	Investigator's choice of either iri...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Overall Number of Participants Analyzed	49	7
Median (95% Confidence Interval) Unit of Measure: months
	1.48 (1.41 to 1.51)	2.63 (1.45 to 2.79)

35.Secondary Outcome


Title	(Phase 3) Comparison of Time to Response in Doublet Arm vs Control Arm Per BICR
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Doublet Arm	Phase 3:Control Arm
Arm/Group Description:	Encorafenib + cetuximab. ...	Investigator's choice of either iri...
Arm/Group Description:	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Overall Number of Participants Analyzed	36	3
Median (95% Confidence Interval) Unit of Measure: months
	1.48 (1.41 to 1.58)	1.45 (1.41 to 2.63)

36.Secondary Outcome


Title	(Phase 3) Comparison of Time to Response in Doublet Arm vs Control Arm Per Investigator
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Doublet Arm	Phase 3:Control Arm
Arm/Group Description:	Encorafenib + cetuximab. ...	Investigator's choice of either iri...
Arm/Group Description:	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Overall Number of Participants Analyzed	31	7
Median (95% Confidence Interval) Unit of Measure: months
	1.48 (1.41 to 1.54)	2.63 (1.45 to 2.79)

37.Secondary Outcome


Title	(Phase 3) Comparison of Time to Response in Triplet Arm vs Doublet Arm Per BICR
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Triplet Arm	Phase 3:Doublet Arm
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...	Encorafenib + cetuximab. ...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	50	36
Median (95% Confidence Interval) Unit of Measure: months
	1.43 (1.41 to 1.51)	1.48 (1.41 to 1.58)

38.Secondary Outcome


Title	(Phase 3) Comparison of Time to Response in Triplet Arm vs Doublet Arm Per Investigator
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Triplet Arm	Phase 3:Doublet Arm
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...	Encorafenib + cetuximab. ...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	49	31
Median (95% Confidence Interval) Unit of Measure: months
	1.48 (1.41 to 1.51)	1.48 (1.41 to 1.54)

39.Secondary Outcome


Title	(Phase 3) Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Patients (QLQ-C30) Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet
Description	The EORTC QLQ-C30 questionnaire consisted of 30 questions generating f...
Description	The EORTC QLQ-C30 questionnaire consisted of 30 questions generating five functional scores (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale score; three symptom scale scores (fatigue, pain, and nausea and vomiting); and six stand alone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and perceived financial burden. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title		Phase 3: Triplet Arm	Phase 3:Doublet Arm	Phase 3:Control Arm
Arm/Group Description:		Encorafenib + binimetinib + cetuxim...	Encorafenib + cetuximab. ...	Investigator's choice of either iri...
Arm/Group Description:		Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Overall Number of Participants Analyzed		224	220	221
Mean (Standard Deviation) Unit of Measure: units on a scale
Baseline	Number Analyzed	209 participants	201 participants	200 participants
Baseline		62.8 (22.18)	60.7 (21.33)	62.8 (21.82)
Cycle 1 Day 1	Number Analyzed	138 participants	133 participants	120 participants
Cycle 1 Day 1		-2.4 (13.44)	-4.3 (16.27)	-3.4 (15.60)
Cycle 2 Day 1	Number Analyzed	181 participants	180 participants	123 participants
Cycle 2 Day 1		-1.6 (19.06)	3.8 (18.46)	-1.9 (22.45)
Cycle 3 Day 1	Number Analyzed	148 participants	142 participants	51 participants
Cycle 3 Day 1		0.7 (18.86)	3.5 (19.96)	-0.2 (24.07)
Cycle 4 Day 1	Number Analyzed	119 participants	105 participants	37 participants
Cycle 4 Day 1		0.2 (15.63)	4.2 (22.17)	1.4 (21.65)
Cycle 5 Day 1	Number Analyzed	99 participants	81 participants	26 participants
Cycle 5 Day 1		-1.1 (18.66)	4.3 (22.09)	-2.2 (22.06)
Cycle 6 Day 1	Number Analyzed	68 participants	60 participants	13 participants
Cycle 6 Day 1		-4.0 (16.76)	5.6 (23.25)	-4.5 (19.43)
Cycle 7 Day 1	Number Analyzed	47 participants	50 participants	10 participants
Cycle 7 Day 1		-2.5 (16.01)	4.3 (21.77)	1.7 (12.30)
Cycle 8 Day 1	Number Analyzed	39 participants	40 participants	7 participants
Cycle 8 Day 1		-2.6 (14.83)	4.2 (16.98)	0.0 (27.64)
Cycle 9 Day 1	Number Analyzed	33 participants	31 participants	7 participants
Cycle 9 Day 1		-5.8 (17.74)	-5.6 (16.44)	-4.8 (12.60)
Cycle 10 Day 1	Number Analyzed	23 participants	24 participants	4 participants
Cycle 10 Day 1		-3.3 (17.90)	-2.8 (16.97)	2.1 (20.83)
Cycle 11 Day 1	Number Analyzed	16 participants	19 participants	1 participants
Cycle 11 Day 1		-5.2 (20.38)	3.9 (15.31)	33.3 ^[1] (NA)
Cycle 12 Day 1	Number Analyzed	14 participants	18 participants	2 participants
Cycle 12 Day 1		0.0 (22.41)	-4.6 (13.77)	4.2 (53.03)
Cycle 13 Day 1	Number Analyzed	9 participants	13 participants	1 participants
Cycle 13 Day 1		0.0 (20.41)	-3.2 (14.25)	0.0 ^[2] (NA)
Cycle 14 Day 1	Number Analyzed	7 participants	7 participants	0 participants
Cycle 14 Day 1		-1.2 (24.26)	-6.0 (15.00)
Cycle 15 Day 1	Number Analyzed	7 participants	6 participants	0 participants
Cycle 15 Day 1		3.6 (33.63)	2.8 (8.61)
Cycle 16 Day 1	Number Analyzed	5 participants	3 participants	0 participants
Cycle 16 Day 1		-16.7 (42.08)	-5.6 (9.62)
Cycle 17 Day 1	Number Analyzed	3 participants	3 participants	0 participants
Cycle 17 Day 1		-27.8 (20.97)	-2.8 (12.73)
Cycle 18 Day 1	Number Analyzed	1 participants	3 participants	0 participants
Cycle 18 Day 1		-16.7 ^[2] (NA)	-8.3 (8.33)
Cycle 19 Day 1	Number Analyzed	1 participants	2 participants	0 participants
Cycle 19 Day 1		0.0 ^[2] (NA)	-8.3 (11.79)
Cycle 20 Day 1	Number Analyzed	1 participants	1 participants	0 participants
Cycle 20 Day 1		-25 ^[2] (NA)	-8 ^[2] (NA)
Cycle 21 Day 1	Number Analyzed	1 participants	1 participants	0 participants
Cycle 21 Day 1		0.0 ^[2] (NA)	-16.7 ^[2] (NA)
Cycle 22 Day 1	Number Analyzed	0 participants	1 participants	0 participants
Cycle 22 Day 1			-16.7 ^[2] (NA)
Cycle 23 Day 1	Number Analyzed	0 participants	1 participants	0 participants
Cycle 23 Day 1			0.0 ^[2] (NA)
End of Treatment	Number Analyzed	74 participants	72 participants	79 participants
End of Treatment		-14.1 (22.66)	-13.1 (21.61)	-15.5 (27.04)
30 Day Follow Up	Number Analyzed	24 participants	16 participants	21 participants
30 Day Follow Up		-17.4 (22.51)	-10.4 (15.96)	-24.6 (24.08)

[1]

Number analyzed is 1 so standard deviation (SD) is not available.

[2]

Number analyzed is 1 so SD is not available.

40.Secondary Outcome


Title	(Phase 3) Change From Baseline in the Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet
Description	FACT-C is a well-characterized and commonly used questionnaire that be...
Description	FACT-C is a well-characterized and commonly used questionnaire that belongs to the Functional Assessment of Chronic Illness Therapy Measurement System (FACIT). The FACT-G (G for general) questionnaire (27 questions) constitutes the core of all subscales and is applicable to all tumor types. The FACT-C questionnaire contains 9 additional questions on symptoms specific to CRC, 2 of which are only answered by patients with ostomy appliances. These 9 CRC-specific questions are categorized as "additional concerns" on the questionnaire and constitute the "colorectal cancer subscale" score. The patient self-reports his/her QoL for the previous 7 days. The overall score is calculated across all items and a higher score reflects better quality of life (QoL). The table summarizes the functional well-being subscale, the individual questions are linearly scaled and combined to form the functional well-being subscale score, which ranges from 0-28 (higher is better QoL).
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title		Phase 3: Triplet Arm	Phase 3:Doublet Arm	Phase 3:Control Arm
Arm/Group Description:		Encorafenib + binimetinib + cetuxim...	Encorafenib + cetuximab. ...	Investigator's choice of either iri...
Arm/Group Description:		Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Overall Number of Participants Analyzed		224	220	221
Mean (Standard Deviation) Unit of Measure: units on a scale
Baseline	Number Analyzed	211 participants	199 participants	200 participants
Baseline		16.3 (6.22)	16.2 (5.9)	16.8 (6.07)
Cycle 1 Day 1	Number Analyzed	142 participants	130 participants	117 participants
Cycle 1 Day 1		-0.2 (3.36)	-0.9 (4.06)	-1.4 (3.32)
Cycle 2 Day 1	Number Analyzed	183 participants	176 participants	123 participants
Cycle 2 Day 1		-0.3 (4.28)	-0.6 (5.08)	-0.9 (4.48)
Cycle 3 Day 1	Number Analyzed	148 participants	137 participants	50 participants
Cycle 3 Day 1		-0.2 (5.15)	-0.2 (5.23)	-0.7 (5.03)
Cycle 4 Day 1	Number Analyzed	119 participants	105 participants	37 participants
Cycle 4 Day 1		0.4 (4.53)	-0.1 (4.66)	-1.8 (6.48)
Cycle 5 Day 1	Number Analyzed	100 participants	81 participants	26 participants
Cycle 5 Day 1		0.7 (6.4)	-0.2 (4.5)	-1.6 (4.58)
Cycle 6 Day 1	Number Analyzed	68 participants	58 participants	13 participants
Cycle 6 Day 1		0.7 (6.05)	0.6 (4.56)	-1.9 (5.3)
Cycle 7 Day 1	Number Analyzed	47 participants	49 participants	10 participants
Cycle 7 Day 1		0.5 (5.85)	-0.1 (4.70)	-0.5 (5.41)
Cycle 8 Day 1	Number Analyzed	40 participants	39 participants	8 participants
Cycle 8 Day 1		0.9 (6.35)	0.2 (4.24)	-2.1 (4.97)
Cycle 9 Day 1	Number Analyzed	32 participants	30 participants	7 participants
Cycle 9 Day 1		-1.9 (4.32)	-0.8 (3.74)	-2.6 (2.30)
Cycle 10 Day 1	Number Analyzed	22 participants	24 participants	4 participants
Cycle 10 Day 1		-1.7 (4.76)	-1.3 (3.59)	0.5 (4.36)
Cycle 11 Day 1	Number Analyzed	17 participants	19 participants	2 participants
Cycle 11 Day 1		-1.5 (4.47)	-0.5 (4.65)	-4.5 (7.78)
Cycle 12 Day 1	Number Analyzed	14 participants	18 participants	2 participants
Cycle 12 Day 1		-1.5 (4.93)	-1.1 (4.61)	-4.5 (9.19)
Cycle 13 Day 1	Number Analyzed	9 participants	13 participants	1 participants
Cycle 13 Day 1		-2.0 (6.76)	-3.2 (5.34)	-8.0 ^[1] (NA)
Cycle 14 Day 1	Number Analyzed	7 participants	7 participants	0 participants
Cycle 14 Day 1		-2.4 (5.22)	-4.0 (5.74)
Cycle 15 Day 1	Number Analyzed	7 participants	6 participants	0 participants
Cycle 15 Day 1		-2.3 (6.85)	-1.5 (4.72)
Cycle 16 Day 1	Number Analyzed	5 participants	3 participants	0 participants
Cycle 16 Day 1		-4.2 (4.02)	-0.7 (0.58)
Cycle 17 Day 1	Number Analyzed	3 participants	3 participants	0 participants
Cycle 17 Day 1		-6.7 (5.51)	-0.7 (4.51)
Cycle 18 Day 1	Number Analyzed	1 participants	3 participants	0 participants
Cycle 18 Day 1		-5.0 ^[1] (NA)	-3.0 (4.36)
Cycle 19 Day 1	Number Analyzed	1 participants	2 participants	0 participants
Cycle 19 Day 1		-7.0 ^[1] (NA)	-6.0 (0.00)
Cycle 20 Day 1	Number Analyzed	1 participants	1 participants	0 participants
Cycle 20 Day 1		-6.0 ^[1] (NA)	-5.0 ^[1] (NA)
Cycle 21 Day 1	Number Analyzed	1 participants	1 participants	0 participants
Cycle 21 Day 1		-9.0	-5.0
Cycle 22 Day 1	Number Analyzed	0 participants	1 participants	0 participants
Cycle 22 Day 1			-12.0 ^[1] (NA)
Cycle 23 Day 1	Number Analyzed	0 participants	1 participants	0 participants
Cycle 23 Day 1			-9.0 ^[1] (NA)
End of Treatment	Number Analyzed	74 participants	73 participants	79 participants
End of Treatment		-2.4 (4.84)	-2.2 (5.14)	-3.1 (6.06)
30 Day Follow Up	Number Analyzed	24 participants	16 participants	21 participants
30 Day Follow Up		-3.5 (6.44)	-0.8 (5.42)	-4.2 (6.41)

[1]

Number analyzed is 1 so SD is not available.

41.Secondary Outcome


Title	(Phase 3) Change From Baseline in the EuroQol-5D-5L (EQ-5D-5L) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet
Description	The EQ-5D-5L contains 1 item for each of 5 dimensions of health-relate...
Description	The EQ-5D-5L contains 1 item for each of 5 dimensions of health-related QoL (i.e., mobility, self-care, usual activities, pain or discomfort and anxiety or depression). Response options for each item varied from having no problems to moderate problems or extreme problems. The EQ-5D-5L (v4.0) is a standardized measure of health utility that provides a single index value for one's health status. The EQ-5D-5L is frequently used for economic evaluations of health care and has been recognized as a valid and reliable instrument for this purpose. The EQ visual analog scale (VAS) is a score that is directly reported by the patient and ranges from 0 to 100 (higher is better quality health).
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title		Phase 3: Triplet Arm	Phase 3:Doublet Arm	Phase 3:Control Arm
Arm/Group Description:		Encorafenib + binimetinib + cetuxim...	Encorafenib + cetuximab. ...	Investigator's choice of either iri...
Arm/Group Description:		Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Overall Number of Participants Analyzed		224	220	221
Mean (Standard Deviation) Unit of Measure: units on a scale
Baseline	Number Analyzed	210 participants	203 participants	199 participants
Baseline		69.0 (19.03)	66.5 (19.51)	68.3 (19.71)
Cycle 1 Day 1	Number Analyzed	141 participants	135 participants	120 participants
Cycle 1 Day 1		0.8 (10.89)	-0.9 (14.09)	-2.1 (15.02)
Cycle 2 Day 1	Number Analyzed	183 participants	181 participants	124 participants
Cycle 2 Day 1		1.4 (14.74)	1.9 (14.81)	-2.4 (17.20)
Cycle 3 Day 1	Number Analyzed	150 participants	141 participants	52 participants
Cycle 3 Day 1		3.0 (13.94)	4.2 (17.32)	-1.4 (17.40)
Cycle 4 Day 1	Number Analyzed	118 participants	105 participants	37 participants
Cycle 4 Day 1		4.0 (13.06)	5.6 (14.87)	-0.4 (15.14)
Cycle 5 Day 1	Number Analyzed	99 participants	80 participants	26 participants
Cycle 5 Day 1		3.3 (14.66)	5.1 (15.11)	2.5 (11.17)
Cycle 6 Day 1	Number Analyzed	66 participants	58 participants	13 participants
Cycle 6 Day 1		1.3 (13.33)	2.9 (16.84)	-3.6 (13.26)
Cycle 7 Day 1	Number Analyzed	46 participants	47 participants	10 participants
Cycle 7 Day 1		1.4 (13.64)	3.6 (16.71)	2.4 (7.44)
Cycle 8 Day 1	Number Analyzed	39 participants	39 participants	8 participants
Cycle 8 Day 1		4.1 (10.77)	2.0 (16.11)	-2.8 (12.95)
Cycle 9 Day 1	Number Analyzed	33 participants	30 participants	7 participants
Cycle 9 Day 1		0.3 (15.16)	-4.0 (12.99)	-8.1 (8.80)
Cycle 10 Day 1	Number Analyzed	23 participants	23 participants	4 participants
Cycle 10 Day 1		0.2 (13.34)	-8.1 (13.68)	-1.8 (2.36)
Cycle 11 Day 1	Number Analyzed	17 participants	18 participants	2 participants
Cycle 11 Day 1		0.2 (13.87)	-0.1 (10.15)	4.0 (8.49)
Cycle 12 Day 1	Number Analyzed	13 participants	17 participants	2 participants
Cycle 12 Day 1		-4.0 (20.11)	-0.6 (11.67)	1.5 (12.02)
Cycle 13 Day 1	Number Analyzed	9 participants	12 participants	1 participants
Cycle 13 Day 1		-3.0 (17.17)	-4.1 (14.41)	-2.0 ^[1] (NA)
Cycle 14 Day 1	Number Analyzed	7 participants	7 participants	0 participants
Cycle 14 Day 1		-4.0 (18.06)	-0.4 (13.99)
Cycle 15 Day 1	Number Analyzed	7 participants	6 participants	0 participants
Cycle 15 Day 1		-3.4 (14.67)	4.2 (7.36)
Cycle 16 Day 1	Number Analyzed	5 participants	3 participants	0 participants
Cycle 16 Day 1		-10.4 (24.87)	3.3 (2.89)
Cycle 17 Day 1	Number Analyzed	3 participants	3 participants	0 participants
Cycle 17 Day 1		-18.3 (20.21)	1.7 (5.77)
Cycle 18 Day 1	Number Analyzed	1 participants	3 participants	0 participants
Cycle 18 Day 1		7.0 ^[1] (NA)	-3.3 (2.89)
Cycle 19 Day 1	Number Analyzed	1 participants	2 participants	0 participants
Cycle 19 Day 1		8.0 ^[1] (NA)	-5.5 (13.44)
Cycle 20 Day 1	Number Analyzed	1 participants	1 participants	0 participants
Cycle 20 Day 1		8.0 ^[1] (NA)	2.0 ^[1] (NA)
Cycle 21 Day 1	Number Analyzed	1 participants	1 participants	0 participants
Cycle 21 Day 1		8.0 ^[1] (NA)	-5.0 ^[1] (NA)
Cycle 22 Day 1	Number Analyzed	0 participants	1 participants	0 participants
Cycle 22 Day 1			-5.0 ^[1] (NA)
Cycle 23 Day 1	Number Analyzed	0 participants	1 participants	0 participants
Cycle 23 Day 1			-5.0 ^[1] (NA)
End of Treatment	Number Analyzed	75 participants	72 participants	80 participants
End of Treatment		-8.5 (17.40)	-8.0 (18.99)	-12.7 (21.34)
30 Day Follow Up	Number Analyzed	24 participants	16 participants	21 participants
30 Day Follow Up		-11.1 (20.23)	-5.9 (20.18)	-11.0 (17.51)

[1]

Number analyzed is 1 so SD is not available.

42.Secondary Outcome


Title	(Phase 3) Change From Baseline in the Patient Global Impression of Change (PGIC) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet
Description	The PGIC is a measure of patients' perceptions of change in their symp...
Description	The PGIC is a measure of patients' perceptions of change in their symptoms over time that can be used as an anchoring method to determine the minimal clinically important difference for other patient reported outcome (PROs). For this assessment, patients 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."
Time Frame	Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Outcome Measure Data

Analysis Population Description


Arm/Group Title		Phase 3: Triplet Arm	Phase 3:Doublet Arm	Phase 3:Control Arm
Arm/Group Description:		Encorafenib + binimetinib + cetuxim...	Encorafenib + cetuximab. ...	Investigator's choice of either iri...
Arm/Group Description:		Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
Overall Number of Participants Analyzed		224	220	221
Mean (Standard Deviation) Unit of Measure: units on a scale
Baseline	Number Analyzed	153 participants	152 participants	149 participants
Baseline		3.8 (1.30)	3.8 (1.30)	3.9 (1.28)
Cycle 1 Day 1	Number Analyzed	91 participants	92 participants	83 participants
Cycle 1 Day 1		-0.1 (0.93)	0.1 (1.21)	0.0 (0.90)
Cycle 2 Day 1	Number Analyzed	127 participants	130 participants	90 participants
Cycle 2 Day 1		-0.7 (1.44)	-0.8 (1.60)	-0.3 (1.52)
Cycle 3 Day 1	Number Analyzed	101 participants	105 participants	37 participants
Cycle 3 Day 1		-0.9 (1.44)	-1.2 (1.53)	-0.5 (1.56)
Cycle 4 Day 1	Number Analyzed	80 participants	79 participants	28 participants
Cycle 4 Day 1		-0.9 (1.49)	-1.1 (1.68)	-0.5 (1.35)
Cycle 5 Day 1	Number Analyzed	66 participants	59 participants	19 participants
Cycle 5 Day 1		-0.9 (1.61)	-1.1 (1.69)	-0.7 (1.41)
Cycle 6 Day 1	Number Analyzed	45 participants	40 participants	9 participants
Cycle 6 Day 1		-0.8 (1.31)	-1.2 (1.70)	-0.8 (1.39)
Cycle 7 Day 1	Number Analyzed	30 participants	36 participants	7 participants
Cycle 7 Day 1		-1.1 (1.44)	-1.0 (1.61)	-1.1 (1.07)
Cycle 8 Day 1	Number Analyzed	23 participants	27 participants	5 participants
Cycle 8 Day 1		-1.2 (1.56)	-1.1 (1.58)	-1.0 (0.71)
Cycle 9 Day 1	Number Analyzed	21 participants	21 participants	5 participants
Cycle 9 Day 1		-0.8 (1.26)	-0.9 (1.37)	-1.0 (0.71)
Cycle 10 Day 1	Number Analyzed	15 participants	17 participants	3 participants
Cycle 10 Day 1		-0.5 (1.51)	-0.6 (1.28)	-0.3 (0.58)
Cycle 11 Day 1	Number Analyzed	13 participants	13 participants	2 participants
Cycle 11 Day 1		-0.9 (1.38)	-1.1 (1.38)	0.0 (0.00)
Cycle 12 Day 1	Number Analyzed	11 participants	12 participants	2 participants
Cycle 12 Day 1		-0.9 (1.45)	-0.8 (1.36)	-0.5 (0.71)
Cycle 13 Day 1	Number Analyzed	8 participants	10 participants	1 participants
Cycle 13 Day 1		-1.3 (1.39)	-0.9 (1.52)	-1.0 ^[1] (NA)
Cycle 14 Day 1	Number Analyzed	7 participants	6 participants	0 participants
Cycle 14 Day 1		-1.1 (1.46)	-1.5 (1.05)
Cycle 15 Day 1	Number Analyzed	6 participants	5 participants	0 participants
Cycle 15 Day 1		-1.2 (1.47)	-1.6 (0.89)
Cycle 16 Day 1	Number Analyzed	4 participants	3 participants	0 participants
Cycle 16 Day 1		-2.0 (0.82)	-0.7 (1.53)
Cycle 17 Day 1	Number Analyzed	3 participants	3 participants	0 participants
Cycle 17 Day 1		-1.3 (1.53)	-1.0 (1.00)
Cycle 18 Day 1	Number Analyzed	1 participants	3 participants	0 participants
Cycle 18 Day 1		-2.0 ^[1] (NA)	-1.0 (1.00)
Cycle 19 Day 1	Number Analyzed	1 participants	2 participants	0 participants
Cycle 19 Day 1		-3.0 ^[1] (NA)	-0.5 (2.12)
Cycle 20 Day 1	Number Analyzed	1 participants	1 participants	0 participants
Cycle 20 Day 1		-3.0 ^[1] (NA)	-2.0 ^[1] (NA)
Cycle 21 Day 1	Number Analyzed	1 participants	1 participants	0 participants
Cycle 21 Day 1		-3.0 ^[1] (NA)	-2.0 ^[1] (NA)
Cycle 22 Day 1	Number Analyzed	0 participants	1 participants	0 participants
Cycle 22 Day 1			-2.0 ^[1] (NA)
Cycle 23 Day 1	Number Analyzed	0 participants	1 participants	0 participants
Cycle 23 Day 1			-2.0 ^[1] (NA)
End of Treatment	Number Analyzed	52 participants	54 participants	63 participants
End of Treatment		0.3 (1.85)	0.1 (1.82)	0.4 (1.58)
30 Day Follow Up	Number Analyzed	18 participants	10 participants	19 participants
30 Day Follow Up		-0.1 (2.08)	0.5 (1.43)	0.7 (1.34)

[1]

Number analyzed is 1 so SD is not available.

43.Secondary Outcome


Title	(Safety Lead-in) Evaluation of the Area Under the Concentration-time Curve (AUC) for Cetuximab
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2

Outcome Measure Data

Analysis Population Description

The pharmacokinetics (PK) set included all patients in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Patients were analyzed according to the actual treatment and dose received.


Arm/Group Title		Combined Safety Lead-in
Arm/Group Description:		Encorafenib + binimetinib + cetuxim...
Arm/Group Description:		Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed		37
Geometric Mean (Geometric Coefficient of Variation) Unit of Measure: ng/mL*h
Cycle 1	Number Analyzed	34 participants
Cycle 1		841000 (22.2%)
Cycle 2	Number Analyzed	32 participants
Cycle 2		970000 (20.6%)

44.Secondary Outcome


Title	(Safety Lead-in) Evaluation of the Area Under the Concentration-time Curve (AUC) for Encorafenib
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2

Outcome Measure Data

Analysis Population Description

The PK set included all patients in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Patients were analyzed according to the actual treatment and dose received.


Arm/Group Title		Combined Safety Lead-in
Arm/Group Description:		Encorafenib + binimetinib + cetuxim...
Arm/Group Description:		Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed		37
Geometric Mean (Geometric Coefficient of Variation) Unit of Measure: ng/mL*h
Cycle 1	Number Analyzed	34 participants
Cycle 1		11300 (61.5%)
Cycle 2	Number Analyzed	29 participants
Cycle 2		6660 (61.7%)

45.Secondary Outcome


Title	(Safety Lead-in) Evaluation of the Area Under the Concentration-time Curve (AUC) for Binimetinib
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2

Outcome Measure Data

Analysis Population Description


Arm/Group Title		Combined Safety Lead-in
Arm/Group Description:		Encorafenib + binimetinib + cetuxim...
Arm/Group Description:		Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed		37
Geometric Mean (Geometric Coefficient of Variation) Unit of Measure: ng/mL*h
Cycle 1	Number Analyzed	35 participants
Cycle 1		1960 (43.6%)
Cycle 2	Number Analyzed	26 participants
Cycle 2		1540 (44.7%)

46.Secondary Outcome


Title	(Safety Lead-in) Evaluation of the Area Under the Concentration-time Curve (AUC) for Metabolite of Binimetinib (AR00426032)
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2

Outcome Measure Data

Analysis Population Description


Arm/Group Title		Combined Safety Lead-in
Arm/Group Description:		Encorafenib + binimetinib + cetuxim...
Arm/Group Description:		Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed		37
Geometric Mean (Geometric Coefficient of Variation) Unit of Measure: ng/mL*h
Cycle 1	Number Analyzed	35 participants
Cycle 1		206 (46.7%)
Cycle 2	Number Analyzed	26 participants
Cycle 2		70.0 (95.5%)

47.Secondary Outcome


Title	(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Cetuximab
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2

Outcome Measure Data

Analysis Population Description


Arm/Group Title		Combined Safety Lead-in
Arm/Group Description:		Encorafenib + binimetinib + cetuxim...
Arm/Group Description:		Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed		37
Geometric Mean (Geometric Coefficient of Variation) Unit of Measure: ng/mL
Cycle 1	Number Analyzed	34 participants
Cycle 1		195000 (22.2%)
Cycle 2	Number Analyzed	32 participants
Cycle 2		199000 (26.8%)

48.Secondary Outcome


Title	(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Encorafenib
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2

Outcome Measure Data

Analysis Population Description


Arm/Group Title		Combined Safety Lead-in
Arm/Group Description:		Encorafenib + binimetinib + cetuxim...
Arm/Group Description:		Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed		37
Geometric Mean (Geometric Coefficient of Variation) Unit of Measure: ng/mL
Cycle 1	Number Analyzed	34 participants
Cycle 1		3360 (65.1%)
Cycle 2	Number Analyzed	29 participants
Cycle 2		2490 (75.6%)

49.Secondary Outcome


Title	(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Binimetinib
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2

Outcome Measure Data

Analysis Population Description


Arm/Group Title		Combined Safety Lead-in
Arm/Group Description:		Encorafenib + binimetinib + cetuxim...
Arm/Group Description:		Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed		37
Geometric Mean (Geometric Coefficient of Variation) Unit of Measure: ng/mL
Cycle 1	Number Analyzed	35 participants
Cycle 1		654 (50.8%)
Cycle 2	Number Analyzed	26 participants
Cycle 2		524 (70.1%)

50.Secondary Outcome


Title	(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Metabolite of Binimetinib (AR00426032)
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2

Outcome Measure Data

Analysis Population Description


Arm/Group Title		Combined Safety Lead-in
Arm/Group Description:		Encorafenib + binimetinib + cetuxim...
Arm/Group Description:		Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed		37
Geometric Mean (Geometric Coefficient of Variation) Unit of Measure: ng/mL
Cycle 1	Number Analyzed	35 participants
Cycle 1		59.9 (50.8%)
Cycle 2	Number Analyzed	26 participants
Cycle 2		20.5 (119%)

51.Secondary Outcome


Title	(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Cetuximab
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2

Outcome Measure Data

Analysis Population Description


Arm/Group Title		Combined Safety Lead-in
Arm/Group Description:		Encorafenib + binimetinib + cetuxim...
Arm/Group Description:		Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed		37
Median (Full Range) Unit of Measure: hours
Cycle 1	Number Analyzed	34 participants
Cycle 1		3.77 (1.83 to 6.05)
Cycle 2	Number Analyzed	32 participants
Cycle 2		3.05 (1.00 to 6.17)

52.Secondary Outcome


Title	(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Encorafenib
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2

Outcome Measure Data

Analysis Population Description


Arm/Group Title		Combined Safety Lead-in
Arm/Group Description:		Encorafenib + binimetinib + cetuxim...
Arm/Group Description:		Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed		37
Median (Full Range) Unit of Measure: hours
Cycle 1	Number Analyzed	34 participants
Cycle 1		2.00 (.883 to 6.25)
Cycle 2	Number Analyzed	29 participants
Cycle 2		2.00 (.950 to 5.73)

53.Secondary Outcome


Title	(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Binimetinib
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2

Outcome Measure Data

Analysis Population Description


Arm/Group Title		Combined Safety Lead-in
Arm/Group Description:		Encorafenib + binimetinib + cetuxim...
Arm/Group Description:		Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed		37
Median (Full Range) Unit of Measure: hours
Cycle 1	Number Analyzed	35 participants
Cycle 1		1.98 (.883 to 5.67)
Cycle 2	Number Analyzed	26 participants
Cycle 2		1.04 (.900 to 4.00)

54.Secondary Outcome


Title	(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Metabolite of Binimetinib (AR00426032)
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2

Outcome Measure Data

Analysis Population Description


Arm/Group Title		Combined Safety Lead-in
Arm/Group Description:		Encorafenib + binimetinib + cetuxim...
Arm/Group Description:		Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed		37
Median (Full Range) Unit of Measure: hours
Cycle 1	Number Analyzed	35 participants
Cycle 1		2.00 (.833 to 5.78)
Cycle 2	Number Analyzed	26 participants
Cycle 2		1.58 (.933 to 6.52)

55.Secondary Outcome


Title	(Safety Lead-in) Evaluation of the Steady-state Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Binimetinib
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Combined Safety Lead-in
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	37
Geometric Mean (Geometric Coefficient of Variation) Unit of Measure: ng/mL
	55.3 (61.5%)

56.Secondary Outcome


Title	(Safety Lead-in) Evaluation of the Steady-state Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Encorafenib
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Combined Safety Lead-in
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	37
Geometric Mean (Geometric Coefficient of Variation) Unit of Measure: ng/mL
	18.9 (191%)

57.Secondary Outcome


Title	(Safety Lead-in) Evaluation of the Steady-state Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Cetuximab
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Combined Safety Lead-in
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	37
Geometric Mean (Geometric Coefficient of Variation) Unit of Measure: ng/mL
	55400 (54.8%)

58.Secondary Outcome


Title	(Safety Lead-in) Evaluation of the Steady-state Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for a Metabolite of Binimetinib
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Combined Safety Lead-in
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
Overall Number of Participants Analyzed	37
Geometric Mean (Geometric Coefficient of Variation) Unit of Measure: ng/mL
	3.41 (68.5%)

59.Secondary Outcome


Title	(Phase 3) Evaluation of the Model-Based Oral Clearance (CL/F) for Encorafenib
Description	The cross-arm CL/F value is based on the theta determined from a popul...
Description	The cross-arm CL/F value is based on the theta determined from a population PK analysis. Data for this Outcome Measure are not reported here because as per plan, the analysis includes pooled data from participants enrolled in multiple studies including those who were not enrolled in this study. The NCTID for those studies for which results have not yet been posted include: NCT01719380, NCT01543698, and NCT01436656. An additional study ARRAY-162-105 is not required to register.
Time Frame	2 and 6 hours post-dose on Day 1 of Cycle 1. Predose and 2 hours post-dose on Day 1 of Cycle 2.

Outcome Measure Data

Analysis Population Description

The analysis set included all patients in the PK set with measurable plasma concentrations of the test drug plus concentrations from subjects from 4 additional clinical studies. Patients were analyzed according to the actual treatment and dose received.


Arm/Group Title	Phase 3: Triplet, Doublet and Control Arm
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib + cetuximab. Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.
Overall Number of Participants Analyzed	394
Geometric Mean (95% Confidence Interval) Unit of Measure: L/h
	16.4 (14.9 to 17.5)

60.Secondary Outcome


Title	(Phase 3) Evaluation of the Model-Based Oral Clearance (CL/F) for Binimetinib
Description	The cross-arm CL/F value is based on the theta determined from a popul...
Description	The cross-arm CL/F value is based on the theta determined from a population PK analysis. Data for this Outcome Measure are not reported here because as per plan, the analysis includes pooled data from participants enrolled in multiple studies including those who were not enrolled in this study. The NCTID for those studies for which results have not yet been posted include: NCT01719380, NCT01543698, and NCT01436656. An additional study ARRAY-162-105 is not required to register.
Time Frame	2 and 6 hours post-dose on Day 1 of Cycle 1. Predose and 2 hours post-dose on Day 1 of Cycle 2.

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Triplet, Doublet and Control Arm
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib + cetuximab. Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.
Overall Number of Participants Analyzed	181
Geometric Mean (95% Confidence Interval) Unit of Measure: L/h
	19.0 (17.7 to 20.6)

61.Secondary Outcome


Title	(Phase 3) Evaluation of the Model-Based Clearance (CL) for Cetuximab
Description	The cross-arm CL/F value is based on the theta determined from a popul...
Description	The cross-arm CL/F value is based on the theta determined from a population PK analysis. Data for this Outcome Measure are not reported here because as per plan, the analysis includes pooled data from participants enrolled in multiple studies including those who were not enrolled in this study. The NCTID for those studies for which results have not yet been posted include: NCT01719380, NCT01543698, and NCT01436656. An additional study ARRAY-162-105 is not required to register.
Time Frame	2 and 6 hours post-dose on Day 1 of Cycle 1. Predose and 2 hours post-dose on Day 1 of Cycle 2.

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Phase 3: Triplet, Doublet and Control Arm
Arm/Group Description:	Encorafenib + binimetinib + cetuxim...
Arm/Group Description:	Encorafenib + binimetinib + cetuximab. Encorafenib + cetuximab. Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.
Overall Number of Participants Analyzed	261
Geometric Mean (95% Confidence Interval) Unit of Measure: L/h
	0.0154 (0.0114 to 0.0225)

Adverse Events

Time Frame	Adverse Events (AE) were collected during the study (duration of safety lead-in and phase 3,approximately 12 months (up to 28 days per cycle)), which began in 09Oct2016 and still ongoing.
Adverse Event Reporting Description	An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.

Arm/Group Title	Combined Safety Lead-in	Phase 3: Triplet Arm	Phase 3: Doublet Arm	Phase 3:Control Arm
Arm/Group Description	Encorafenib + binimetinib + cetuxim...	Encorafenib + binimetinib + cetuxim...	Encorafenib + cetuximab. ...	Investigator's choice of either iri...
Arm/Group Description	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.	Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care.
All-Cause Mortality
	Combined Safety Lead-in	Phase 3: Triplet Arm	Phase 3: Doublet Arm	Phase 3:Control Arm
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/37 (2.70%)	7/222 (3.15%)	5/216 (2.31%)	11/193 (5.70%)
Serious Adverse Events Serious Adverse Events
	Combined Safety Lead-in	Phase 3: Triplet Arm	Phase 3: Doublet Arm	Phase 3:Control Arm
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	22/37 (59.46%)	93/222 (41.89%)	71/216 (32.87%)	71/193 (36.79%)
Blood and lymphatic system disorders
Anaemia ^* 1	1/37 (2.70%)	4/222 (1.80%)	1/216 (0.46%)	1/193 (0.52%)
Pulmonary embolism ^* 1	1/37 (2.70%)	8/222 (3.60%)	3/216 (1.39%)	4/193 (2.07%)
Bacteraemia ^* 1	0/37 (0.00%)	3/222 (1.35%)	0/216 (0.00%)	1/193 (0.52%)
Febrile neutropenia ^* 1	0/37 (0.00%)	0/222 (0.00%)	0/216 (0.00%)	5/193 (2.59%)
Infusion-related reaction ^* 1	5/37 (13.51%)	1/222 (0.45%)	7/216 (3.24%)	6/193 (3.11%)
Blood creatinine increased ^* 1	2/37 (5.41%)	2/222 (0.90%)	0/216 (0.00%)	0/193 (0.00%)
Neutropenia ^* 1	0/37 (0.00%)	0/222 (0.00%)	0/216 (0.00%)	1/193 (0.52%)
Cardiac disorders
Cardiac arrest ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Cardio-respiratory ^* 1	0/37 (0.00%)	0/222 (0.00%)	1/216 (0.46%)	1/193 (0.52%)
Atrial fibrillation ^* 1	0/37 (0.00%)	0/222 (0.00%)	3/216 (1.39%)	0/193 (0.00%)
Gastrointestinal disorders
Diarrhoea ^* 1	1/37 (2.70%)	12/222 (5.41%)	1/216 (0.46%)	10/193 (5.18%)
Vomiting ^* 1	2/37 (5.41%)	3/222 (1.35%)	2/216 (0.93%)	3/193 (1.55%)
Gastrointestinal perforation ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Ileus ^* 1	0/37 (0.00%)	5/222 (2.25%)	3/216 (1.39%)	2/193 (1.04%)
Intestinal obstruction ^* 1	0/37 (0.00%)	6/222 (2.70%)	14/216 (6.48%)	8/193 (4.15%)
Large intestine perforation ^* 1	1/37 (2.70%)	3/222 (1.35%)	2/216 (0.93%)	2/193 (1.04%)
Gastrointestinal haemorrhage ^* 1	0/37 (0.00%)	0/222 (0.00%)	1/216 (0.46%)	0/193 (0.00%)
Subileus ^* 1	0/37 (0.00%)	0/222 (0.00%)	0/216 (0.00%)	1/193 (0.52%)
Abdominal pain ^* 1	0/37 (0.00%)	4/222 (1.80%)	3/216 (1.39%)	4/193 (2.07%)
Bile duct obstruction ^* 1	0/37 (0.00%)	2/222 (0.90%)	3/216 (1.39%)	2/193 (1.04%)
Large intestinal obstruction ^* 1	0/37 (0.00%)	1/222 (0.45%)	3/216 (1.39%)	0/193 (0.00%)
Subileus ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	3/193 (1.55%)
Small intestinal obstruction ^* 1	0/37 (0.00%)	2/222 (0.90%)	0/216 (0.00%)	6/193 (3.11%)
Colitis ^* 1	1/37 (2.70%)	2/222 (0.90%)	0/216 (0.00%)	0/193 (0.00%)
Abdominal distention ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Constipation ^* 1	0/37 (0.00%)	1/222 (0.45%)	1/216 (0.46%)	1/193 (0.52%)
Duodenal obstruction ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Dyspepsia ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Gastritis ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Gastrointtestinal perforation ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Haematemesis ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
intestinal perforation ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Melaena ^* 1	0/37 (0.00%)	1/222 (0.45%)	1/216 (0.46%)	0/193 (0.00%)
Pancreatitis ^* 1	0/37 (0.00%)	1/222 (0.45%)	1/216 (0.46%)	0/193 (0.00%)
Pancreatitis acute ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Pancreatitis relapsing ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Rectal stenosis ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Rectal ulcer ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Abdominal hernia ^* 1	0/37 (0.00%)	0/222 (0.00%)	0/216 (0.00%)	1/193 (0.52%)
Anal haemorrhage ^* 1	0/37 (0.00%)	0/222 (0.00%)	1/216 (0.46%)	0/193 (0.00%)
Ascites ^* 1	0/37 (0.00%)	0/222 (0.00%)	1/216 (0.46%)	1/193 (0.52%)
Enterocolitis ^* 1	0/37 (0.00%)	0/222 (0.00%)	1/216 (0.46%)	1/193 (0.52%)
Impaired gastric emptying ^* 1	0/37 (0.00%)	0/222 (0.00%)	1/216 (0.46%)	0/193 (0.00%)
Large intestine ulcer ^* 1	1/37 (2.70%)	0/222 (0.00%)	0/216 (0.00%)	0/193 (0.00%)
Proctalgia ^* 1	0/37 (0.00%)	0/222 (0.00%)	0/216 (0.00%)	1/193 (0.52%)
General disorders
Death ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Pain ^* 1	0/37 (0.00%)	1/222 (0.45%)	1/216 (0.46%)	2/193 (1.04%)
Asthenia ^* 1	0/37 (0.00%)	0/222 (0.00%)	1/216 (0.46%)	1/193 (0.52%)
Hepatobiliary disorders
Hepatic failure ^* 1	0/37 (0.00%)	9/222 (4.05%)	0/216 (0.00%)	0/193 (0.00%)
Jaundice ^* 1	0/37 (0.00%)	1/222 (0.45%)	1/216 (0.46%)	1/193 (0.52%)
Immune system disorders
Anaphylactic reaction ^* 1	0/37 (0.00%)	0/222 (0.00%)	0/216 (0.00%)	1/193 (0.52%)
Infections and infestations
Peritonitis ^* 1	0/37 (0.00%)	0/222 (0.00%)	0/216 (0.00%)	1/193 (0.52%)
Respiratory tract infection ^* 1	0/37 (0.00%)	0/222 (0.00%)	0/216 (0.00%)	1/193 (0.52%)
Sepsis ^* 1	0/37 (0.00%)	6/222 (2.70%)	2/216 (0.93%)	0/193 (0.00%)
Abdominal wall abscess ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Biliary tract infection ^* 1	0/37 (0.00%)	1/222 (0.45%)	1/216 (0.46%)	0/193 (0.00%)
Cholangitis infective ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Endocarditis ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Erysipelas ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Gastrintestinal infection ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Urosepsis ^* 1	0/37 (0.00%)	1/222 (0.45%)	1/216 (0.46%)	0/193 (0.00%)
Wound abscess ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Abdominal abscess ^* 1	1/37 (2.70%)	0/222 (0.00%)	1/216 (0.46%)	0/193 (0.00%)
Abscess limb ^* 1	0/37 (0.00%)	0/222 (0.00%)	0/216 (0.00%)	1/193 (0.52%)
Anal abscess ^* 1	0/37 (0.00%)	0/222 (0.00%)	0/216 (0.00%)	1/193 (0.52%)
Bacteria sepsis ^* 1	1/37 (2.70%)	0/222 (0.00%)	0/216 (0.00%)	1/193 (0.52%)
Campylobacter gastroenteritis ^* 1	0/37 (0.00%)	0/222 (0.00%)	0/216 (0.00%)	1/193 (0.52%)
Metabolism and nutrition disorders
Nausea ^* 1	1/37 (2.70%)	12/222 (5.41%)	3/216 (1.39%)	1/193 (0.52%)
General physical health deterioration ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	2/193 (1.04%)
Asthenia ^* 1	0/37 (0.00%)	4/222 (1.80%)	0/216 (0.00%)	0/193 (0.00%)
Fatigue ^* 1	1/37 (2.70%)	2/222 (0.90%)	0/216 (0.00%)	0/193 (0.00%)
Dehydration ^* 1	1/37 (2.70%)	2/222 (0.90%)	1/216 (0.46%)	1/193 (0.52%)
Decreased appetite ^* 1	1/37 (2.70%)	0/222 (0.00%)	0/216 (0.00%)	1/193 (0.52%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colorectal cancer metastatic ^* 1	0/37 (0.00%)	2/222 (0.90%)	0/216 (0.00%)	0/193 (0.00%)
Malignant neoplasm progression ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Neoplasm progression ^* 1	0/37 (0.00%)	1/222 (0.45%)	1/216 (0.46%)	1/193 (0.52%)
Colon cancer ^* 1	1/37 (2.70%)	0/222 (0.00%)	2/216 (0.93%)	0/193 (0.00%)
Colon cancer metastatic ^* 1	0/37 (0.00%)	0/222 (0.00%)	2/216 (0.93%)	1/193 (0.52%)
Colorectal cancer ^* 1	0/37 (0.00%)	0/222 (0.00%)	1/216 (0.46%)	1/193 (0.52%)
Cancer pain ^* 1	0/37 (0.00%)	1/222 (0.45%)	5/216 (2.31%)	1/193 (0.52%)
Nervous system disorders
Pyrexia ^* 1	2/37 (5.41%)	4/222 (1.80%)	1/216 (0.46%)	0/193 (0.00%)
Cerebral ischaemia ^* 1	0/37 (0.00%)	0/222 (0.00%)	0/216 (0.00%)	1/193 (0.52%)
Epilepsy ^* 1	0/37 (0.00%)	0/222 (0.00%)	0/216 (0.00%)	1/193 (0.52%)
Psychiatric disorders
Anxiety ^* 1	0/37 (0.00%)	2/222 (0.90%)	0/216 (0.00%)	0/193 (0.00%)
Renal and urinary disorders
Acute kidney injury ^* 1	0/37 (0.00%)	7/222 (3.15%)	4/216 (1.85%)	1/193 (0.52%)
Urinary tract infection ^* 1	4/37 (10.81%)	2/222 (0.90%)	5/216 (2.31%)	1/193 (0.52%)
Haematuria ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Hydronephrosis ^* 1	1/37 (2.70%)	1/222 (0.45%)	0/216 (0.00%)	1/193 (0.52%)
Nephritis ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Renal failure ^* 1	2/37 (5.41%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Urinary retention ^* 1	0/37 (0.00%)	1/222 (0.45%)	0/216 (0.00%)	0/193 (0.00%)
Respiratory, thoracic and mediastinal disorders
Aspiration ^* 1	0/37 (0.00%)	0/222 (0.00%)	2/216 (0.93%)	0/193 (0.00%)
Respiratory distress ^* 1	0/37 (0.00%)	0/222 (0.00%)	0/216 (0.00%)	1/193 (0.52%)
Respiratory failure ^* 1	0/37 (0.00%)	1/222 (0.45%)	1/216 (0.46%)	3/193 (1.55%)
1 Term from vocabulary, MedDRA (21.0) * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Combined Safety Lead-in	Phase 3: Triplet Arm	Phase 3: Doublet Arm	Phase 3:Control Arm
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	37/37 (100.00%)	217/222 (97.75%)	212/216 (98.15%)	188/193 (97.41%)
Blood and lymphatic system disorders
Anaemia ^* 1	16/37 (43.24%)	80/222 (36.04%)	35/216 (16.20%)	37/193 (19.17%)
Hypomagnesaemia ^* 1	6/37 (16.22%)	20/222 (9.01%)	22/216 (10.19%)	17/193 (8.81%)
Hypokalaemia ^* 1	3/37 (8.11%)	15/222 (6.76%)	13/216 (6.02%)	27/193 (13.99%)
Neutropenia ^* 1	1/37 (2.70%)	3/222 (1.35%)	1/216 (0.46%)	36/193 (18.65%)
Neutrophil count decreased ^* 1	0/37 (0.00%)	1/222 (0.45%)	1/216 (0.46%)	21/193 (10.88%)
Cardiac disorders
Palpitations ^* 1	2/37 (5.41%)	3/222 (1.35%)	3/216 (1.39%)	1/193 (0.52%)
Eye disorders
Vision blurred ^* 1	12/37 (32.43%)	25/222 (11.26%)	8/216 (3.70%)	1/193 (0.52%)
Dry eye ^* 1	4/37 (10.81%)	6/222 (2.70%)	7/216 (3.24%)	2/193 (1.04%)
Retinal detachment ^* 1	2/37 (5.41%)	6/222 (2.70%)	1/216 (0.46%)	0/193 (0.00%)
Gastrointestinal disorders
Diarrhoea ^* 1	28/37 (75.68%)	137/222 (61.71%)	72/216 (33.33%)	93/193 (48.19%)
Nausea ^* 1	22/37 (59.46%)	100/222 (45.05%)	74/216 (34.26%)	80/193 (41.45%)
Vomiting ^* 1	18/37 (48.65%)	85/222 (38.29%)	46/216 (21.30%)	56/193 (29.02%)
Abdominal pain ^* 1	14/37 (37.84%)	65/222 (29.28%)	49/216 (22.69%)	48/193 (24.87%)
Decreased appetite ^* 1	14/37 (37.84%)	63/222 (28.38%)	68/216 (31.48%)	52/193 (26.94%)
Constipation ^* 1	14/37 (37.84%)	55/222 (24.77%)	33/216 (15.28%)	35/193 (18.13%)
Abdominal pain upper ^* 1	4/37 (10.81%)	20/222 (9.01%)	19/216 (8.80%)	15/193 (7.77%)
Dyspepsia ^* 1	4/37 (10.81%)	16/222 (7.21%)	7/216 (3.24%)	7/193 (3.63%)
Flatulence ^* 1	0/37 (0.00%)	13/222 (5.86%)	6/216 (2.78%)	3/193 (1.55%)
Rectal haemorrhage ^* 1	3/37 (8.11%)	12/222 (5.41%)	5/216 (2.31%)	1/193 (0.52%)
Dry Mouth ^* 1	2/37 (5.41%)	11/222 (4.95%)	8/216 (3.70%)	7/193 (3.63%)
Gastroesophageal reflux disease ^* 1	2/37 (5.41%)	11/222 (4.95%)	4/216 (1.85%)	5/193 (2.59%)
Abdominal distension ^* 1	2/37 (5.41%)	9/222 (4.05%)	12/216 (5.56%)	8/193 (4.15%)
Intestinal obstruction ^* 1	0/37 (0.00%)	8/222 (3.60%)	12/216 (5.56%)	8/193 (4.15%)
General disorders
Chills ^* 1	4/37 (10.81%)	13/222 (5.86%)	6/216 (2.78%)	3/193 (1.55%)
Malaise ^* 1	6/37 (16.22%)	6/222 (2.70%)	5/216 (2.31%)	11/193 (5.70%)
Infections and infestations
Pyrexia ^* 1	15/37 (40.54%)	45/222 (20.27%)	35/216 (16.20%)	27/193 (13.99%)
Urinary tract infection ^* 1	7/37 (18.92%)	18/222 (8.11%)	16/216 (7.41%)	6/193 (3.11%)
Paronychia ^* 1	6/37 (16.22%)	17/222 (7.66%)	8/216 (3.70%)	17/193 (8.81%)
Rash pustular ^* 1	5/37 (13.51%)	13/222 (5.86%)	4/216 (1.85%)	4/193 (2.07%)
Conjunctivitis ^* 1	2/37 (5.41%)	10/222 (4.50%)	8/216 (3.70%)	2/193 (1.04%)
Cystitis ^* 1	2/37 (5.41%)	6/222 (2.70%)	1/216 (0.46%)	1/193 (0.52%)
Injury, poisoning and procedural complications
Infusion related reaction ^* 1	3/37 (8.11%)	5/222 (2.25%)	20/216 (9.26%)	13/193 (6.74%)
Investigations
Blood creatine phosphokinase increased ^* 1	13/37 (35.14%)	20/222 (9.01%)	1/216 (0.46%)	3/193 (1.55%)
Blood creatine increased ^* 1	11/37 (29.73%)	18/222 (8.11%)	4/216 (1.85%)	1/193 (0.52%)
Alanine aminotransferase increased ^* 1	6/37 (16.22%)	15/222 (6.76%)	12/216 (5.56%)	12/193 (6.22%)
Aspartate aminotransferase increased ^* 1	7/37 (18.92%)	13/222 (5.86%)	8/216 (3.70%)	13/193 (6.74%)
Ejection fraction decreased ^* 1	5/37 (13.51%)	8/222 (3.60%)	0/216 (0.00%)	0/193 (0.00%)
Blood bilirubin increased ^* 1	3/37 (8.11%)	6/222 (2.70%)	10/216 (4.63%)	8/193 (4.15%)
White blood cell count decrease ^* 1	0/37 (0.00%)	1/222 (0.45%)	1/216 (0.46%)	14/193 (7.25%)
Metabolism and nutrition disorders
Fatigue ^* 1	20/37 (54.05%)	73/222 (32.88%)	65/216 (30.09%)	53/193 (27.46%)
Asthenia ^* 1	6/37 (16.22%)	55/222 (24.77%)	46/216 (21.30%)	49/193 (25.39%)
Weight decreased ^* 1	3/37 (8.11%)	24/222 (10.81%)	21/216 (9.72%)	11/193 (5.70%)
Hypomagnesaemia ^* 1	6/37 (16.22%)	20/222 (9.01%)	22/216 (10.19%)	17/193 (8.81%)
Hypoalbuminaemia ^* 1	4/37 (10.81%)	16/222 (7.21%)	5/216 (2.31%)	5/193 (2.59%)
Hyperglycaemia ^* 1	1/37 (2.70%)	10/222 (4.50%)	7/216 (3.24%)	5/193 (2.59%)
Dehydration ^* 1	2/37 (5.41%)	9/222 (4.05%)	4/216 (1.85%)	8/193 (4.15%)
Musculoskeletal and connective tissue disorders
PPE syndrome ^* 1	6/37 (16.22%)	28/222 (12.61%)	9/216 (4.17%)	14/193 (7.25%)
Back Pain ^* 1	8/37 (21.62%)	25/222 (11.26%)	22/216 (10.19%)	23/193 (11.92%)
Oedema peripheral ^* 1	6/37 (16.22%)	24/222 (10.81%)	18/216 (8.33%)	13/193 (6.74%)
Arthralgia ^* 1	9/37 (24.32%)	23/222 (10.36%)	41/216 (18.98%)	1/193 (0.52%)
Myalgia ^* 1	7/37 (18.92%)	18/222 (8.11%)	29/216 (13.43%)	4/193 (2.07%)
Pain in extremity ^* 1	3/37 (8.11%)	15/222 (6.76%)	22/216 (10.19%)	1/193 (0.52%)
Musculoskeletal pain ^* 1	2/37 (5.41%)	6/222 (2.70%)	27/216 (12.50%)	3/193 (1.55%)
Muscle spasms ^* 1	2/37 (5.41%)	17/222 (7.66%)	3/216 (1.39%)	4/193 (2.07%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour Pain ^* 1	4/37 (10.81%)	3/222 (1.35%)	0/216 (0.00%)	2/193 (1.04%)
Nervous system disorders
Headache ^* 1	6/37 (16.22%)	16/222 (7.21%)	42/216 (19.44%)	5/193 (2.59%)
Insomnia ^* 1	2/37 (5.41%)	11/222 (4.95%)	24/216 (11.11%)	11/193 (5.70%)
Dizziness ^* 1	8/37 (21.62%)	13/222 (5.86%)	14/216 (6.48%)	15/193 (7.77%)
Neuropathy peripheral ^* 1	1/37 (2.70%)	13/222 (5.86%)	8/216 (3.70%)	5/193 (2.59%)
Dysgeusia ^* 1	6/37 (16.22%)	11/222 (4.95%)	9/216 (4.17%)	7/193 (3.63%)
Peripheral sensory neuropathy ^* 1	6/37 (16.22%)	8/222 (3.60%)	4/216 (1.85%)	4/193 (2.07%)
Syncope ^* 1	2/37 (5.41%)	3/222 (1.35%)	2/216 (0.93%)	0/193 (0.00%)
Psychiatric disorders
Insomnia ^* 1	2/37 (5.41%)	11/222 (4.95%)	24/216 (11.11%)	11/193 (5.70%)
Depression ^* 1	2/37 (5.41%)	4/222 (1.80%)	4/216 (1.85%)	1/193 (0.52%)
Renal and urinary disorders
Acute kidney injury ^* 1	1/37 (2.70%)	11/222 (4.95%)	4/216 (1.85%)	1/193 (0.52%)
Haematuria ^* 1	2/37 (5.41%)	10/222 (4.50%)	4/216 (1.85%)	4/193 (2.07%)
Respiratory, thoracic and mediastinal disorders
Cough ^* 1	5/37 (13.51%)	23/222 (10.36%)	16/216 (7.41%)	10/193 (5.18%)
Dyspnoea ^* 1	12/37 (32.43%)	17/222 (7.66%)	23/216 (10.65%)	17/193 (8.81%)
Pulmonary embolism ^* 1	2/37 (5.41%)	10/222 (4.50%)	3/216 (1.39%)	8/193 (4.15%)
Epistaxis ^* 1	1/37 (2.70%)	7/222 (3.15%)	15/216 (6.94%)	7/193 (3.63%)
Dysphonia ^* 1	1/37 (2.70%)	5/222 (2.25%)	11/216 (5.09%)	3/193 (1.55%)
Rhinnorrhoea ^* 1	3/37 (8.11%)	5/222 (2.25%)	5/216 (2.31%)	1/193 (0.52%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform ^* 1	25/37 (67.57%)	108/222 (48.65%)	63/216 (29.17%)	76/193 (39.38%)
Dry Skin ^* 1	19/37 (51.35%)	46/222 (20.72%)	24/216 (11.11%)	13/193 (6.74%)
Rash ^* 1	3/37 (8.11%)	42/222 (18.92%)	25/216 (11.57%)	27/193 (13.99%)
Stomatitis ^* 1	6/37 (16.22%)	31/222 (13.96%)	12/216 (5.56%)	44/193 (22.80%)
Pruritus ^* 1	3/37 (8.11%)	28/222 (12.61%)	20/216 (9.26%)	9/193 (4.66%)
Melanocytic naevus ^* 1	1/37 (2.70%)	1/222 (0.45%)	31/216 (14.35%)	0/193 (0.00%)
Palmar-planar erythrodysaesthesia ^* 1	6/37 (16.22%)	28/222 (12.61%)	9/216 (4.17%)	14/193 (7.25%)
Rash maculo-papular ^* 1	5/37 (13.51%)	18/222 (8.11%)	17/216 (7.87%)	11/193 (5.70%)
Skin fissures ^* 1	9/37 (24.32%)	15/222 (6.76%)	5/216 (2.31%)	10/193 (5.18%)
Erythema ^* 1	2/37 (5.41%)	7/222 (3.15%)	10/216 (4.63%)	4/193 (2.07%)
Eczema ^* 1	2/37 (5.41%)	5/222 (2.25%)	1/216 (0.46%)	1/193 (0.52%)
Skin hyperpigmentation ^* 1	2/37 (5.41%)	1/222 (0.45%)	16/216 (7.41%)	2/193 (1.04%)
Skin lesion ^* 1	0/37 (0.00%)	1/222 (0.45%)	17/216 (7.87%)	1/193 (0.52%)
Vascular disorders
Hypotension ^* 1	3/37 (8.11%)	7/222 (3.15%)	9/216 (4.17%)	3/193 (1.55%)
Hypertension ^* 1	4/37 (10.81%)	6/222 (2.70%)	7/216 (3.24%)	6/193 (3.11%)
1 Term from vocabulary, MedDRA (21.0) * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The terms and conditions of the sponsor's agreements with its investigators may vary. However, the sponsor does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e., data from all sites) in the clinical trials.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Study Director
Organization:	Pfizer
Phone:	1-800-718-1021
EMail:	ClinicalTrials.gov_Inquiries@pfizer.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kopetz S, Grothey A, Yaeger R, Van Cutsem E, Desai J, Yoshino T, Wasan H, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Pfeiffer P, Orlov S, Lonardi S, Elez E, Kim TW, Schellens JHM, Guo C, Krishnan A, Dekervel J, Morris V, Calvo Ferrandiz A, Tarpgaard LS, Braun M, Gollerkeri A, Keir C, Maharry K, Pickard M, Christy-Bittel J, Anderson L, Sandor V, Tabernero J. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer. N Engl J Med. 2019 Oct 24;381(17):1632-1643. doi: 10.1056/NEJMoa1908075. Epub 2019 Sep 30.

Van Cutsem E, Huijberts S, Grothey A, Yaeger R, Cuyle PJ, Elez E, Fakih M, Montagut C, Peeters M, Yoshino T, Wasan H, Desai J, Ciardiello F, Gollerkeri A, Christy-Bittel J, Maharry K, Sandor V, Schellens JHM, Kopetz S, Tabernero J. Binimetinib, Encorafenib, and Cetuximab Triplet Therapy for Patients With BRAF V600E-Mutant Metastatic Colorectal Cancer: Safety Lead-In Results From the Phase III BEACON Colorectal Cancer Study. J Clin Oncol. 2019 Jun 10;37(17):1460-1469. doi: 10.1200/JCO.18.02459. Epub 2019 Mar 20.

Layout table for additonal information

Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT02928224
Other Study ID Numbers:	ARRAY-818-302 BEACON CRC ( Other Identifier: Alias Study Number ) 2015-005805-35 ( EudraCT Number ) C4221009 ( Other Identifier: Pfizer )
First Submitted:	August 16, 2016
First Posted:	October 10, 2016
Results First Submitted:	May 6, 2020
Results First Posted:	July 14, 2020
Last Update Posted:	February 17, 2021

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