Page last updated: 2024-10-16

carbamates and Metastase

carbamates has been researched along with Metastase in 25 studies

Research Excerpts

Excerpt	Relevance	Reference
"A multicenter, retrospective case series investigation of consecutive BRAF-mutant patients with melanoma brain metastases (MBMs) treated with a combination of BRAF inhibitor encorafenib and MEK inhibitor binimetinib was conducted to evaluate the antitumor response."	7.96	Intracranial antitumor activity with encorafenib plus binimetinib in patients with melanoma brain metastases: A case series. ( Amaria, RN; Amin, A; Davies, MA; Davis, JM; Diab, A; Glitza, IC; Holbrook, K; Lutzky, J; Patel, SP; Tawbi, H, 2020)
"To create a cost-effectiveness model to compare doublet therapy (encorafenib plus cetuximab) with standard chemotherapy (cetuximab plus irinotecan or cetuximab plus folinic acid, fluorouracil, and irinotecan) in treating patients with metastatic BRAF variant colorectal cancer."	4.02	Evaluation of the Cost-effectiveness of Doublet Therapy in Metastatic BRAF Variant Colorectal Cancer. ( Huntington, SF; Lacy, J; O'Hara, M; Patel, KK; Stein, S, 2021)
"A multicenter, retrospective case series investigation of consecutive BRAF-mutant patients with melanoma brain metastases (MBMs) treated with a combination of BRAF inhibitor encorafenib and MEK inhibitor binimetinib was conducted to evaluate the antitumor response."	3.96	Intracranial antitumor activity with encorafenib plus binimetinib in patients with melanoma brain metastases: A case series. ( Amaria, RN; Amin, A; Davies, MA; Davis, JM; Diab, A; Glitza, IC; Holbrook, K; Lutzky, J; Patel, SP; Tawbi, H, 2020)
"Prostate cancer bone metastases are characterized by their ability to induce osteoblastic lesions and local bone formation."	1.32	Notch signaling and ERK activation are important for the osteomimetic properties of prostate cancer bone metastatic cell lines. ( Abdulkadir, SA; McDonald, JM; Zayzafoon, M, 2004)

Research

Studies (25)

Timeframe	Studies, this research(%)	All Research%
pre-1990	13 (52.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	2 (8.00)	29.6817
2010's	4 (16.00)	24.3611
2020's	6 (24.00)	2.80

Authors

Authors	Studies
Holbrook, K	1
Lutzky, J	1
Davies, MA	1
Davis, JM	1
Glitza, IC	1
Amaria, RN	1
Diab, A	1
Patel, SP	1
Amin, A	1
Tawbi, H	1
Shahjehan, F	1
Kamatham, S	1
Chandrasekharan, C	1
Kasi, PM	1
Tholander, B	1
Koliadi, A	1
Botling, J	1
Dahlstrand, H	1
Von Heideman, A	1
Ahlström, H	1
Öberg, K	1
Ullenhag, GJ	1
Patel, KK	1
Stein, S	1
Lacy, J	1
O'Hara, M	1
Huntington, SF	1
Tabernero, J	1
Grothey, A	1
Van Cutsem, E	1
Yaeger, R	1
Wasan, H	1
Yoshino, T	1
Desai, J	1
Ciardiello, F	1
Loupakis, F	1
Hong, YS	1
Steeghs, N	1
Guren, TK	1
Arkenau, HT	1
Garcia-Alfonso, P	1
Elez, E	1
Gollerkeri, A	1
Maharry, K	1
Christy-Bittel, J	1
Kopetz, S	1
Usama, SM	1
Inagaki, F	1
Kobayashi, H	1
Schnermann, MJ	1
Al-Salama, ZT	1
Schaper-Gerhardt, K	1
Okoye, S	1
Herbst, R	1
Ulrich, J	1
Terheyden, P	1
Pföhler, C	1
Utikal, JS	1
Kreuter, A	1
Mohr, P	1
Dippel, E	1
Satzger, I	1
Sucker, A	1
Schadendorf, D	1
Ugurel, S	1
Gutzmer, R	1
Shirley, M	1
Anforth, RM	1
Carlos, GR	1
Scolyer, RA	1
Chou, S	1
Fernandez-Peñas, P	1
Zayzafoon, M	1
Abdulkadir, SA	1
McDonald, JM	1
Thomas, JP	1
Moore, T	1
Kraut, EH	1
Balcerzak, SP	1
Galloway, S	1
Vandre, DD	1
Karev, NI	1
Garin, AM	1
Blokhina, NG	1
Pershin, MP	1
Trapeznikova, MF	1
Atassi, G	1
Tagnon, HJ	1
Veksler, IG	1
Riabukha, VN	1
Chubinskaia, SG	1
Shvarts, GIa	1
Welvaart, K	1
Merrin, CE	1
Mittelman, A	2
Murphy, GP	2
Gailani, S	1
Blais, M	1
de Leval, J	1
Petit, R	1
Bouffioux, C	1
Szendröi, Z	2
Könyves, I	1
Szendi, L	1
Eckhardt, S	2
Hartay, F	1
Kocsár, L	1
Karika, Z	1
Füzi, M	1
Tarján, G	1
Reischel, G	1
Müntzing, J	1
Shukla, SK	1
Chu, TM	1
Baba, T	1
Kimura, NT	1
Kanematsu, T	1
Aoki, K	1
Lindberg, B	1
Jönsson, G	1
Garcia, H	1
Guerrero, A	1

Clinical Trials (1)

Trial Overview

Trial			Phase	Enrollment	Study Type	Start Date	Status
A Multicenter, Randomized, Open-label, 3-Arm Phase 3 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 Encorafe[NCT02928224]			Phase 3	702 participants (Actual)	Interventional	2016-10-13	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

(Phase 3) Comparison of Duration of Response (DOR) in Doublet Arm vs Control Arm Per BICR

DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. (NCT02928224)
Timeframe: From time of response to PD or death due to underlying disease (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm)

Intervention	Months (Median)
Phase 3: Doublet Arm	6.06
Phase 3:Control Arm	NA

(Phase 3) Comparison of Duration of Response (DOR) in Doublet Arm vs Control Arm Per Investigator

Intervention	Months (Median)
Phase 3: Doublet Arm	5.70
Phase 3:Control Arm	5.75

(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Control Arm Per BICR

DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. (NCT02928224)
Timeframe: From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm)

Intervention	Months (Median)
Phase 3: Triplet Arm	4.80
Phase 3:Control Arm	NA

(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Control Arm Per Investigator

DOR was defined as the time from first radiographic evidence of response to the earliest documented disease progression (PD) or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. (NCT02928224)
Timeframe: From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm)

Intervention	Months (Median)
Phase 3: Triplet Arm	4.80
Phase 3:Control Arm	5.75

(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Doublet Arm by BICR

DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. (NCT02928224)
Timeframe: From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm)

Intervention	Months (Median)
Phase 3: Triplet Arm	4.80
Phase 3:Doublet Arm	6.06

(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Doublet Arm by Investigator

DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. (NCT02928224)
Timeframe: From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm)

Intervention	Months (Median)
Phase 3: Triplet Arm	4.80
Phase 3:Doublet Arm	5.70

(Phase 3) Comparison of Objective Response Rate (ORR) in Doublet Arm vs Control Arm Per BICR

ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. (NCT02928224)
Timeframe: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Intervention	Percentage of participants (Number)
Phase 3: Doublet Arm	20.4
Phase 3:Control Arm	1.9

(Phase 3) Comparison of Objective Response Rate (ORR) in Doublet Arm vs Control Arm Per Investigator

Intervention	Percentage of participants (Number)
Phase 3: Doublet Arm	15.9
Phase 3:Control Arm	3.7

(Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Control Arm Per Investigator

Intervention	Percentage of participants (Number)
Phase 3: Triplet Arm	26.1
Phase 3:Control Arm	3.7

(Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Doublet Arm Per BICR

Intervention	Percentage of participants (Number)
Phase 3: Triplet Arm	26.1
Phase 3: Doublet Arm	20.4

(Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Doublet Arm Per Investigator

Intervention	Percentage of participants (Number)
Phase 3: Triplet Arm	26.1
Phase 3: Doublet Arm	15.9

(Phase 3) Comparison of Progression-Free Survival (PFS) in Doublet Arm vs Control Arm Per BICR

PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. (NCT02928224)
Timeframe: From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm)

Intervention	Months (Median)
Phase 3: Doublet Arm	4.21
Phase 3:Control Arm	1.51

(Phase 3) Comparison of Progression-Free Survival (PFS) in Doublet Arm vs Control Arm Per Investigator

Intervention	Months (Median)
Phase 3: Doublet Arm	4.27
Phase 3:Control Arm	1.58

(Phase 3) Comparison of Progression-Free Survival (PFS) in Triplet Arm vs Control Arm Per BICR

PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. (NCT02928224)
Timeframe: From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm)

Intervention	Months (Median)
Phase 3: Triplet Arm	4.30
Phase 3:Control Arm	1.51

(Phase 3) Comparison of Progression-free Survival (PFS) in Triplet Arm vs Control Arm Per Investigator

PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. (NCT02928224)
Timeframe: From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm)

Intervention	Months (Median)
Phase 3: Triplet Arm	4.47
Phase 3:Control Arm	1.58

(Phase 3) Comparison of Progression-Free Survival (PFS) in Triplet Arm vs Doublet Arm Per BICR

PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. (NCT02928224)
Timeframe: From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm)

Intervention	Months (Median)
Phase 3: Triplet Arm	4.30
Phase 3: Doublet Arm	4.21

(Phase 3) Comparison of Progression-Free Survival (PFS) in Triplet Arm vs Doublet Arm Per Investigator

PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. (NCT02928224)
Timeframe: From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm)

Intervention	Months (Median)
Phase 3: Triplet Arm	4.47
Phase 3: Doublet Arm	4.27

(Phase 3) Comparison of Time to Response in Doublet Arm vs Control Arm Per BICR

Time to response was defined as the time from first dose to first radiographic evidence of response. (NCT02928224)
Timeframe: From first dose to first radiographic evidence of response (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm)

Intervention	Months (Median)
Phase 3: Doublet Arm	1.48
Phase 3:Control Arm	1.45

(Phase 3) Comparison of Time to Response in Doublet Arm vs Control Arm Per Investigator

Intervention	Months (Median)
Phase 3: Doublet Arm	1.48
Phase 3:Control Arm	2.63

(Phase 3) Comparison of Time to Response in Triplet Arm vs Control Arm Per BICR

Time to response was defined as the time from first dose to first radiographic evidence of response. (NCT02928224)
Timeframe: From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm)

Intervention	Months (Median)
Phase 3: Triplet Arm	1.43
Phase 3:Control Arm	1.45

(Phase 3) Comparison of Time to Response in Triplet Arm vs Control Arm Per Investigator

Time to response was defined as the time from first dose to first radiographic evidence of response. (NCT02928224)
Timeframe: From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm)

Intervention	Months (Median)
Phase 3: Triplet Arm	1.48
Phase 3:Control Arm	2.63

(Phase 3) Comparison of Time to Response in Triplet Arm vs Doublet Arm Per BICR

Time to response was defined as the time from first dose to first radiographic evidence of response. (NCT02928224)
Timeframe: From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm)

Intervention	Months (Median)
Phase 3: Triplet Arm	1.43
Phase 3:Doublet Arm	1.48

(Phase 3) Comparison of Time to Response in Triplet Arm vs Doublet Arm Per Investigator

Time to response was defined as the time from first dose to first radiographic evidence of response. (NCT02928224)
Timeframe: From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm)

Intervention	Months (Median)
Phase 3: Triplet Arm	1.48
Phase 3:Doublet Arm	1.48

(Phase 3) Evaluation of the Model-Based Clearance (CL) for Cetuximab

The reported cross-arm CL/F value is a fixed-effect parameter determined from a population PK analysis. The analysis included pooled data from participants enrolled in multiple studies including those who were not enrolled in this study. The NCTID include: NCT01719380, NCT01543698, and NCT01436656. An additional study ARRAY-162-105 is not required to register. (NCT02928224)
Timeframe: 2 and 6 hours post-dose on Day 1 of Cycle 1, Predose and 2 hours post-dose on Day 1 of Cycle 2 (each cycle of 28 days)

Intervention	Liter/hour (Geometric Mean)
Pharmacokinetic Population of Encorafenib	0.0154

(Phase 3) Evaluation of the Model-Based Oral Clearance (CL/F) for Binimetinib

Intervention	Liter/hour (Geometric Mean)
Pharmacokinetic Population of Encorafenib	19.0

(Phase 3) Evaluation of the Model-Based Oral Clearance (CL/F) for Encorafenib

Intervention	Liter/hour (Geometric Mean)
Pharmacokinetic Population of Encorafenib	16.4

(Phase 3) Objective 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

ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of complete response (CR) or partial response (PR), where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 millimeter [mm] short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. (NCT02928224)
Timeframe: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Intervention	Percentage of participants (Number)
Phase 3: Triplet Arm	26.1
Phase 3:Control Arm	1.9

(Phase 3) Overall Survival (OS) in Doublet Arm vs. Control Arm

OS was defined as the time from randomization to death due to any cause. (NCT02928224)
Timeframe: From randomization to death due to any cause until 204 deaths were observed (maximum treatment exposure of 89.7 weeks for doublet arm and 52.4 weeks for control arm)

Intervention	Months (Median)
Phase 3: Doublet Arm	9.40
Phase 3:Control Arm	5.88

(Phase 3) Overall Survival (OS) in Triplet Arm vs. Doublet Arm

Intervention	Months (Median)
Phase 3: Triplet Arm	9.82
Phase 3: Doublet Arm	9.40

(Phase 3) Overall Survival (OS) of Triplet Arm vs. Control Arm - Final Analysis

OS was defined as the time from randomization to death due to any cause. (NCT02928224)
Timeframe: From randomization to death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm)

Intervention	Months (Median)
Phase 3: Triplet Arm	9.82
Phase 3:Control Arm	5.88

(Phase 3) Overall Survival (OS) of Triplet Arm vs. Control Arm - Interim Analysis

OS was defined as the time from randomization to death due to any cause. (NCT02928224)
Timeframe: From randomization to death due to any cause until 204 deaths were observed (maximum treatment exposure of 89.1 weeks for triplet arm and 52.4 weeks for control arm)

Intervention	Months (Median)
Phase 3: Triplet Arm	9.03
Phase 3: Control Arm	5.42

(Safety Lead-in) Duration of Response (DOR) by BICR

DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. (NCT02928224)
Timeframe: From time of response to the earliest documented PD or death due to underlying disease (maximum treatment exposure of 280 weeks)

Intervention	Months (Median)
Combined Safety Lead-in	8.15

(Safety Lead-in) Duration of Response (DOR) by Investigator

DOR was defined as the time from first radiographic evidence of response to the earliest documented disease progression (PD) or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. (NCT02928224)
Timeframe: From time of response to the earliest documented PD or death due to underlying disease (maximum treatment exposure of 280 weeks)

Intervention	Months (Median)
Combined Safety Lead-in	6.47

(Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for a Metabolite of Binimetinib

(NCT02928224)
Timeframe: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

Intervention	Nanogram/milliliter (Geometric Mean)
Combined Safety Lead-in	3.41

(Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Binimetinib

(NCT02928224)
Timeframe: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

Intervention	Nanogram/milliliter (Geometric Mean)
Combined Safety Lead-in	55.3

(Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Cetuximab

(NCT02928224)
Timeframe: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

Intervention	Nanogram/milliliter (Geometric Mean)
Combined Safety Lead-in	55400

(Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Encorafenib

(NCT02928224)
Timeframe: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

Intervention	Nanogram/milliliter (Geometric Mean)
Combined Safety Lead-in	18.9

(Safety Lead-in) Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to Adverse Events (AEs) - Interim Analysis

An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. Number of participants with dose interruptions, dose modifications and dose discontinuations due to AEs were reported in this outcome measure. (NCT02928224)
Timeframe: Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)

Intervention	Participants (Count of Participants)
Combined Safety Lead-in	26

(Safety Lead-in) Number of Participants With Adverse Events (AEs)

An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. Number of participants reporting AEs were reported in this outcome measure. (NCT02928224)
Timeframe: Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)

Intervention	Participants (Count of Participants)
Combined Safety Lead-in	37

(Safety Lead-in) Number of Participants With Dose-Limiting Toxicities (DLTs)

(NCT02928224)
Timeframe: Cycle 1 (up to 28 days)

Intervention	Participants (Count of Participants)
Combined Safety Lead-in (CSLI)	5

(Safety Lead-in) Objective Response Rate (ORR) by BICR

ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. (NCT02928224)
Timeframe: From start of study treatment until 30 days post last dose of study treatment (maximum treatment exposure of 280 weeks)

Intervention	Percentage of participants (Number)
Combined Safety Lead-in	41.7

(Safety Lead-in) Objective Response Rate (ORR) by Investigator

ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. (NCT02928224)
Timeframe: From start of study treatment until 30 days post last dose of study treatment (maximum treatment exposure of 280 weeks)

Intervention	Percentage of participants (Number)
Combined Safety Lead-in	52.8

(Safety Lead-in) Progression-Free Survival (PFS) by BICR

Intervention	Months (Median)
Combined Safety Lead-in	5.59

(Safety Lead-in) Progression-Free Survival (PFS) by Investigator

Intervention	Months (Median)
Combined Safety Lead-in	8.08

(Safety Lead-in) Time to Response by BICR

Intervention	Months (Median)
Combined Safety Lead-in	1.45

(Safety Lead-in) Time to Response by Investigator

Intervention	Months (Median)
Combined Safety Lead-in	1.45

Phase 3: Number of Participants With Clinically Notable Shifts in Urinalysis Laboratory Parameters

Clinically notable shifts was defined as worsening by at least 2 grades or to >= Grade 3 based on CTCAE version 4.03 where Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life threatening and Grade 5: death. (NCT02928224)
Timeframe: From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks)

Intervention	Participants (Count of Participants)
Phase 3: Triplet Arm	8
Phase 3: Doublet Arm	8
Phase 3: Control Arm	5

(Phase 3) Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Participants (QLQ-C30) Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet

The EORTC QLQ-C30 questionnaire consisted of 30 questions generating 5 functional scores (physical, role, cognitive, emotional, & social); a global health (GH) status/global quality of life scale score; 3 symptom scale scores (fatigue, pain, & nausea & vomiting); & 6 standalone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, & diarrhea) & perceived financial burden. All items were graded by severity experienced during previous week & used 4-point-scale (1: not at all, 2: a little, 3: quite a bit, 4: very much). The scores were converted to health-related quality of life (HRQoL) scale ranging from 0-100. Higher scores indicating higher response levels (i.e., higher functioning, higher symptom severity). (NCT02928224)
Timeframe: Baseline, Cycle(C)1 Day(D)1 , C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days)

Intervention	Units on a scale (Mean)
	Baseline	Change at Cycle 1 Day 1	Change at Cycle 2 Day 1	Change at Cycle 3 Day 1	Change at Cycle 4 Day 1	Change at Cycle 5 Day 1	Change at Cycle 6 Day 1	Change at Cycle 7 Day 1	Change at Cycle 8 Day 1	Change at Cycle 9 Day 1	Change at Cycle 10 Day 1	Change at Cycle 11 Day 1	Change at Cycle 12 Day 1	Change at Cycle 13 Day 1	Change at End of Treatment	Change at 30 Day Follow Up
Phase 3:Control Arm	62.8	-3.4	-1.9	-0.2	1.4	-2.2	-4.5	1.7	0.0	-4.8	2.1	33.3	4.2	0.0	-15.5	-24.6

(Phase 3) Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Participants (QLQ-C30) Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet

Intervention	Units on a scale (Mean)
	Baseline	Change at Cycle 1 Day 1	Change at Cycle 2 Day 1	Change at Cycle 3 Day 1	Change at Cycle 4 Day 1	Change at Cycle 5 Day 1	Change at Cycle 6 Day 1	Change at Cycle 7 Day 1	Change at Cycle 8 Day 1	Change at Cycle 9 Day 1	Change at Cycle 10 Day 1	Change at Cycle 11 Day 1	Change at Cycle 12 Day 1	Change at Cycle 13 Day 1	Change at Cycle 14 Day 1	Change at Cycle 15 Day 1	Change at Cycle 16 Day 1	Change at Cycle 17 Day 1	Change at Cycle 18 Day 1	Change at Cycle 19 Day 1	Change at Cycle 20 Day 1	Change at Cycle 21 Day 1	Change at End of Treatment	Change at 30 Day Follow Up
Phase 3: Triplet Arm	62.8	-2.4	-1.6	0.7	0.2	-1.1	-4.0	-2.5	-2.6	-5.8	-3.3	-5.2	0.0	0.0	-1.2	3.6	-16.7	-27.8	-16.7	0.0	-25	0.0	-14.1	-17.4

(Phase 3) Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Participants (QLQ-C30) Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet

Intervention	Units on a scale (Mean)
	Baseline	Change at Cycle 1 Day 1	Change at Cycle 2 Day 1	Change at Cycle 3 Day 1	Change at Cycle 4 Day 1	Change at Cycle 5 Day 1	Change at Cycle 6 Day 1	Change at Cycle 7 Day 1	Change at Cycle 8 Day 1	Change at Cycle 9 Day 1	Change at Cycle 10 Day 1	Change at Cycle 11 Day 1	Change at Cycle 12 Day 1	Change at Cycle 13 Day 1	Change at Cycle 14 Day 1	Change at Cycle 15 Day 1	Change at Cycle 16 Day 1	Change at Cycle 17 Day 1	Change at Cycle 18 Day 1	Change at Cycle 19 Day 1	Change at Cycle 20 Day 1	Change at Cycle 21 Day 1	Change at Cycle 22 Day 1	Change at Cycle 23 Day 1	Change at End of Treatment	Change at 30 Day Follow Up
Phase 3:Doublet Arm	60.7	-4.3	3.8	3.5	4.2	4.3	5.6	4.3	4.2	-5.6	-2.8	3.9	-4.6	-3.2	-6.0	2.8	-5.6	-2.8	-8.3	-8.3	-8	-16.7	-16.7	0.0	-13.1	-10.4

(Phase 3) Change From Baseline in the EuroQol-5D-5L Visual Analog Scale (EQ-5D-5L VAS) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet

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 participant and ranges from 0 to 100 (higher is better quality health). (NCT02928224)
Timeframe: Baseline,Cycle (C)1 Day (D)1, C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days)

Intervention	Units on a scale (Mean)
	Baseline	Change at Cycle 1 Day 1	Change at Cycle 2 Day 1	Change at Cycle 3 Day 1	Change at Cycle 4 Day 1	Change at Cycle 5 Day 1	Change at Cycle 6 Day 1	Change at Cycle 7 Day 1	Change at Cycle 8 Day 1	Change at Cycle 9 Day 1	Change at Cycle 10 Day 1	Change at Cycle 11 Day 1	Change at Cycle 12 Day 1	Change at Cycle 13 Day 1	Change at End of Treatment	Change at 30 Day Follow Up
Phase 3:Control Arm	68.3	-2.1	-2.4	-1.4	-0.4	2.5	-3.6	2.4	-2.8	-8.1	-1.8	4.0	1.5	-2.0	-12.7	-11.0

(Phase 3) Change From Baseline in the EuroQol-5D-5L Visual Analog Scale (EQ-5D-5L VAS) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet

Intervention	Units on a scale (Mean)
	Baseline	Change at Cycle 1 Day 1	Change at Cycle 2 Day 1	Change at Cycle 3 Day 1	Change at Cycle 4 Day 1	Change at Cycle 5 Day 1	Change at Cycle 6 Day 1	Change at Cycle 7 Day 1	Change at Cycle 8 Day 1	Change at Cycle 9 Day 1	Change at Cycle 10 Day 1	Change at Cycle 11 Day 1	Change at Cycle 12 Day 1	Change at Cycle 13 Day 1	Change at Cycle 14 Day 1	Change at Cycle 15 Day 1	Change at Cycle 16 Day 1	Change at Cycle 17 Day 1	Change at Cycle 18 Day 1	Change at Cycle 19 Day 1	Change at Cycle 20 Day 1	Change at Cycle 21 Day 1	Change at End of Treatment	Change at 30 Day Follow Up
Phase 3: Triplet Arm	69.0	0.8	1.4	3.0	4.0	3.3	1.3	1.4	4.1	0.3	0.2	0.2	-4.0	-3.0	-4.0	-3.4	-10.4	-18.3	7.0	8.0	8.0	8.0	-8.5	-11.1

(Phase 3) Change From Baseline in the EuroQol-5D-5L Visual Analog Scale (EQ-5D-5L VAS) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet

Intervention	Units on a scale (Mean)
	Baseline	Change at Cycle 1 Day 1	Change at Cycle 2 Day 1	Change at Cycle 3 Day 1	Change at Cycle 4 Day 1	Change at Cycle 5 Day 1	Change at Cycle 6 Day 1	Change at Cycle 7 Day 1	Change at Cycle 8 Day 1	Change at Cycle 9 Day 1	Change at Cycle 10 Day 1	Change at Cycle 11 Day 1	Change at Cycle 12 Day 1	Change at Cycle 13 Day 1	Change at Cycle 14 Day 1	Change at Cycle 15 Day 1	Change at Cycle 16 Day 1	Change at Cycle 17 Day 1	Change at Cycle 18 Day 1	Change at Cycle 19 Day 1	Change at Cycle 20 Day 1	Change at Cycle 21 Day 1	Change at Cycle 22 Day 1	Change at Cycle 23 Day 1	Change at End of Treatment	Change at 30 Day Follow Up
Phase 3:Doublet Arm	66.5	-0.9	1.9	4.2	5.6	5.1	2.9	3.6	2.0	-4.0	-8.1	-0.1	-0.6	-4.1	-0.4	4.2	3.3	1.7	-3.3	-5.5	2.0	-5.0	-5.0	-5.0	-8.0	-5.9

(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

FACT-C= Functional Assessment of Chronic Illness Therapy (FACIT), which assessed HRQoL of cancer participants & participants with other chronic illnesses. It consists of total 36 items (27 items of general version of FACT-C and disease-specific subscale containing 9 CRC-specific items), summarized to 5 subscales: physical well-being (7 items), functional well-being (7 items), social/family well-being (7 items); all 3 subscales range:0-28, emotional well-being (6 items) range: 0-24, colorectal cancer subscale (9 items) range: 0-36; higher subscale score= better QoL. All single-item measures range: 0= 'Not at all' to 4= 'Very much'. Table summarizes functional well-being subscale, individual questions are linearly scaled & combined to form functional well-being subscale score (range 0-28). High score represents better QoL. (NCT02928224)
Timeframe: Baseline,Cycle (C)1 Day (D)1, C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days)

Intervention	Units on a scale (Mean)
	Baseline	Change at Cycle 1 Day 1	Change at Cycle 2 Day 1	Change at Cycle 3 Day 1	Change at Cycle 4 Day 1	Change at Cycle 5 Day 1	Change at Cycle 6 Day 1	Change at Cycle 7 Day 1	Change at Cycle 8 Day 1	Change at Cycle 9 Day 1	Change at Cycle 10 Day 1	Change at Cycle 11 Day 1	Change at Cycle 12 Day 1	Change at Cycle 13 Day 1	Change at End of Treatment	Change at 30 Day Follow Up
Phase 3:Control Arm	16.8	-1.4	-0.9	-0.7	-1.8	-1.6	-1.9	-0.5	-2.1	-2.6	0.5	-4.5	-4.5	-8.0	-3.1	-4.2

(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

Intervention	Units on a scale (Mean)
	Baseline	Change at Cycle 1 Day 1	Change at Cycle 2 Day 1	Change at Cycle 3 Day 1	Change at Cycle 4 Day 1	Change at Cycle 5 Day 1	Change at Cycle 6 Day 1	Change at Cycle 7 Day 1	Change at Cycle 8 Day 1	Change at Cycle 9 Day 1	Change at Cycle 10 Day 1	Change at Cycle 11 Day 1	Change at Cycle 12 Day 1	Change at Cycle 13 Day 1	Change at Cycle 14 Day 1	Change at Cycle 15 Day 1	Change at Cycle 16 Day 1	Change at Cycle 17 Day 1	Change at Cycle 18 Day 1	Change at Cycle 19 Day 1	Change at Cycle 20 Day 1	Change at Cycle 21 Day 1	Change at End of Treatment	Change at 30 Day Follow Up
Phase 3: Triplet Arm	16.3	-0.2	-0.3	-0.2	0.4	0.7	0.7	0.5	0.9	-1.9	-1.7	-1.5	-1.5	-2.0	-2.4	-2.3	-4.2	-6.7	-5.0	-7.0	-6.0	-9.0	-2.4	-3.5

(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

Intervention	Units on a scale (Mean)
	Baseline	Change at Cycle 1 Day 1	Change at Cycle 2 Day 1	Change at Cycle 3 Day 1	Change at Cycle 4 Day 1	Change at Cycle 5 Day 1	Change at Cycle 6 Day 1	Change at Cycle 7 Day 1	Change at Cycle 8 Day 1	Change at Cycle 9 Day 1	Change at Cycle 10 Day 1	Change at Cycle 11 Day 1	Change at Cycle 12 Day 1	Change at Cycle 13 Day 1	Change at Cycle 14 Day 1	Change at Cycle 15 Day 1	Change at Cycle 16 Day 1	Change at Cycle 17 Day 1	Change at Cycle 18 Day 1	Change at Cycle 19 Day 1	Change at Cycle 20 Day 1	Change at Cycle 21 Day 1	Change at Cycle 22 Day 1	Change at Cycle 23 Day 1	Change at End of Treatment	Change at 30 Day Follow Up
Phase 3:Doublet Arm	16.2	-0.9	-0.6	-0.2	-0.1	-0.2	0.6	-0.1	0.2	-0.8	-1.3	-0.5	-1.1	-3.2	-4.0	-1.5	-0.7	-0.7	-3.0	-6.0	-5.0	-5.0	-12.0	-9.0	-2.2	-0.8

(Phase 3) Change From Baseline in the Participant Global Impression of Change (PGIC) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet

"The PGIC is a measure of participant's 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 participant reported outcome (PROs). For this assessment, participants 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." (NCT02928224)
Timeframe: Baseline,Cycle (C)1 Day (D)1, C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days)

Intervention	Units on a scale (Mean)
	Baseline	Change at Cycle 1 Day 1	Change at Cycle 2 Day 1	Change at Cycle 3 Day 1	Change at Cycle 4 Day 1	Change at Cycle 5 Day 1	Change at Cycle 6 Day 1	Change at Cycle 7 Day 1	Change at Cycle 8 Day 1	Change at Cycle 9 Day 1	Change at Cycle 10 Day 1	Change at Cycle 11 Day 1	Change at Cycle 12 Day 1	Change at Cycle 13 Day 1	Change at End of Treatment	Change at 30 Day Follow Up
Phase 3:Control Arm	3.9	0.0	-0.3	-0.5	-0.5	-0.7	-0.8	-1.1	-1.0	-1.0	-0.3	0.0	-0.5	-1.0	0.4	0.7

(Phase 3) Change From Baseline in the Participant Global Impression of Change (PGIC) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet

Intervention	Units on a scale (Mean)
	Baseline	Change at Cycle 1 Day 1	Change at Cycle 2 Day 1	Change at Cycle 3 Day 1	Change at Cycle 4 Day 1	Change at Cycle 5 Day 1	Change at Cycle 6 Day 1	Change at Cycle 7 Day 1	Change at Cycle 8 Day 1	Change at Cycle 9 Day 1	Change at Cycle 10 Day 1	Change at Cycle 11 Day 1	Change at Cycle 12 Day 1	Change at Cycle 13 Day 1	Change at Cycle 14 Day 1	Change at Cycle 15 Day 1	Change at Cycle 16 Day 1	Change at Cycle 17 Day 1	Change at Cycle 18 Day 1	Change at Cycle 19 Day 1	Change at Cycle 20 Day 1	Change at Cycle 21 Day 1	Change at End of Treatment	Change at 30 Day Follow Up
Phase 3: Triplet Arm	3.8	-0.1	-0.7	-0.9	-0.9	-0.9	-0.8	-1.1	-1.2	-0.8	-0.5	-0.9	-0.9	-1.3	-1.1	-1.2	-2.0	-1.3	-2.0	-3.0	-3.0	-3.0	0.3	-0.1

(Phase 3) Change From Baseline in the Participant Global Impression of Change (PGIC) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet

Intervention	Units on a scale (Mean)
	Baseline	Change at Cycle 1 Day 1	Change at Cycle 2 Day 1	Change at Cycle 3 Day 1	Change at Cycle 4 Day 1	Change at Cycle 5 Day 1	Change at Cycle 6 Day 1	Change at Cycle 7 Day 1	Change at Cycle 8 Day 1	Change at Cycle 9 Day 1	Change at Cycle 10 Day 1	Change at Cycle 11 Day 1	Change at Cycle 12 Day 1	Change at Cycle 13 Day 1	Change at Cycle 14 Day 1	Change at Cycle 15 Day 1	Change at Cycle 16 Day 1	Change at Cycle 17 Day 1	Change at Cycle 18 Day 1	Change at Cycle 19 Day 1	Change at Cycle 20 Day 1	Change at Cycle 21 Day 1	Change at Cycle 22 Day 1	Change at Cycle 23 Day 1	Change at End of Treatment	Change at 30 Day Follow Up
Phase 3:Doublet Arm	3.8	0.1	-0.8	-1.2	-1.1	-1.1	-1.2	-1.0	-1.1	-0.9	-0.6	-1.1	-0.8	-0.9	-1.5	-1.6	-0.7	-1.0	-1.0	-0.5	-2.0	-2.0	-2.0	-2.0	0.1	0.5

(Safety Lead-in) Evaluation of the Area Under the Concentration-Time Curve From Zero to the Last Measurable Time Point (AUClast) for Binimetinib

(NCT02928224)
Timeframe: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

Intervention	Nanogram/milliliter *hour (Geometric Mean)
	Cycle 1	Cycle 2
Combined Safety Lead-in	1960	1540

(Safety Lead-in) Evaluation of the Area Under the Concentration-Time Curve From Zero to the Last Measurable Time Point (AUClast) for Cetuximab

(NCT02928224)
Timeframe: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

Intervention	Nanogram/milliliter *hour (Geometric Mean)
	Cycle 1	Cycle 2
Combined Safety Lead-in	841000	970000

(Safety Lead-in) Evaluation of the Area Under the Concentration-Time Curve From Zero to the Last Measurable Time Point (AUClast) for Encorafenib

(NCT02928224)
Timeframe: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

Intervention	Nanogram/milliliter *hour (Geometric Mean)
	Cycle 1	Cycle 2
Combined Safety Lead-in	11300	6660

(Safety Lead-in) Evaluation of the Area Under the Concentration-time Curve From Zero to the Last Measurable Time Point (AUClast) for Metabolite of Binimetinib (AR00426032)

(NCT02928224)
Timeframe: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

Intervention	Nanogram/milliliter *hour (Geometric Mean)
	Cycle 1	Cycle 2
Combined Safety Lead-in	206	70.0

(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Binimetinib

(NCT02928224)
Timeframe: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

Intervention	Nanogram/milliliter (Geometric Mean)
	Cycle 1	Cycle 2
Combined Safety Lead-in	654	524

(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Cetuximab

(NCT02928224)
Timeframe: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

Intervention	Nanogram/milliliter (Geometric Mean)
	Cycle 1	Cycle 2
Combined Safety Lead-in	195000	199000

(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Encorafenib

(NCT02928224)
Timeframe: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

Intervention	Nanogram/milliliter (Geometric Mean)
	Cycle 1	Cycle 2
Combined Safety Lead-in	3360	2490

(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Metabolite of Binimetinib (AR00426032)

(NCT02928224)
Timeframe: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

Intervention	Nanogram/milliliter (Geometric Mean)
	Cycle 1	Cycle 2
Combined Safety Lead-in	59.9	20.5

(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Binimetinib

(NCT02928224)
Timeframe: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

Intervention	Hours (Median)
	Cycle 1	Cycle 2
Combined Safety Lead-in	1.98	1.04

(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Cetuximab

(NCT02928224)
Timeframe: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

Intervention	Hours (Median)
	Cycle 1	Cycle 2
Combined Safety Lead-in	3.77	3.05

(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Encorafenib

(NCT02928224)
Timeframe: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

Intervention	Hours (Median)
	Cycle 1	Cycle 2
Combined Safety Lead-in	2.00	2.00

(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Metabolite of Binimetinib (AR00426032)

(NCT02928224)
Timeframe: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

Intervention	Hours (Median)
	Cycle 1	Cycle 2
Combined Safety Lead-in	2.00	1.58

(Safety Lead-in) Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to Adverse Events (AEs) - Final Analysis

An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. Number of participants according to incidence of dose interruptions, dose modifications and dose discontinuations due to AEs were reported in this outcome measure. (NCT02928224)
Timeframe: From start of study treatment until 30 days post last dose of study treatment (maximum treatment exposure of 280 weeks)

Intervention	Participants (Count of Participants)
	Dose interruptions	Dose modifications	Discontinuation due to AEs
Combined Safety Lead-in	30	16	8

Phase 3: Number of Participants With Clinically Notable Shifts in Hematology and Coagulation Laboratory Parameters

Clinically notable shifts was defined as worsening by at least 2 grades or to more than or equal to (>=) Grade 3 based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 where Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life threatening and Grade 5: death. (NCT02928224)
Timeframe: From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks)

Intervention	Participants (Count of Participants)
	Activated Partial Thromboplastin Time - Hyper	Hemoglobin - Hyper	Hemoglobin - Hypo	Leukocytes - Hyper	Leukocytes - Hypo	Lymphocytes - Hyper	Lymphocytes - Hypo	Neutrophils - Hypo	Platelets - Hypo	Prothrombin Intl. Normalized Ratio - Hyper
Phase 3: Doublet Arm	9	0	30	0	9	3	47	8	5	2
Phase 3: Triplet Arm	9	0	97	0	2	12	25	4	1	3
Phase 3:Control Arm	4	0	17	0	51	4	57	65	4	2

Phase 3: Number of Participants With Clinically Notable Shifts in Serum Chemistry Laboratory Parameters

Intervention	Participants (Count of Participants)
	Alanine Aminotransferase - Hyper	Albumin - Hypo	Alkaline Phosphatase - Hyper	Aspartate Aminotransferase - Hyper	Bilirubin - Hyper	Calcium - Hyper	Calcium - Hypo	Creatine Kinase - Hyper	Creatinine - Hyper	Glucose - Hyper	Glucose - Hypo	Magnesium - Hyper	Magnesium - Hypo	Potassium - Hyper	Potassium - Hypo	Sodium - Hyper	Sodium - Hypo	Troponin I - Hyper	Urate - Hyper
Phase 3: Control Arm	10	17	18	9	12	0	7	3	6	4	1	2	9	5	9	2	5	0	1
Phase 3: Doublet Arm	7	16	12	7	13	0	8	1	11	16	0	1	4	10	7	1	4	0	2
Phase 3: Triplet Arm	11	50	13	11	11	1	15	18	45	8	4	0	11	14	5	1	10	0	4

Phase 3: Number of Participants With Newly Occurring Clinically Notable Electrocardiogram (ECG) Values

Newly occurring clinically notable changes was defined as participants not meeting the criterion at baseline and meeting criterion post-baseline. The criterion included: heart rate- decrease from baseline > 25% and to a value < 50 and increase from baseline > 25% and to a value > 100. QT interval- new > 450 (millisecond) msec, new > 480 msec, new > 500 msec, increase from baseline > 30 msec and increase from baseline > 60 msec. QTcF- new > 450 msec, new > 480 msec, new > 500 msec, increase from baseline > 30 msec and increase from baseline > 60 msec. (NCT02928224)
Timeframe: From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks)

Intervention	Participants (Count of Participants)
	Heart Rate - Decrease from baseline > 25% and to a value < 50	Heart Rate - Increase from baseline > 25% and to a value > 100	QT Interval - New > 450 millisecond (msec)	QT Interval - New > 480 msec	QT Interval - New > 500 msec	QT Interval - increase from baseline > 30 msec	QT Interval - increase from baseline > 60 msec	QTcF - New > 450 msec	QTcF - New > 480 msec	QTcF - New > 500 msec	QTcF - increase from baseline > 30 msec	QTcF - increase from baseline > 60 msec
Phase 3: Control Arm	0	28	7	2	0	32	10	23	5	2	24	5
Phase 3: Doublet Arm	4	24	30	7	5	99	21	51	18	6	75	20
Phase 3: Triplet Arm	1	27	17	4	3	97	22	39	9	1	59	12

Phase 3: Number of Participants With Newly Occurring Clinically Notable Vital Sign Abnormalities

Newly occurring clinically notable changes was defined as participants not meeting the criterion at baseline and meeting criterion post-baseline. The criterion included: low/high systolic blood pressure (SBP): <= 90 millimeters of mercury (mmHg) with decrease from baseline of >= 20mmHg or >= 160mmHg with increase from baseline of >= 20mmHg, low or high diastolic blood pressure (DBP): <= 50mmHg with decrease from baseline of >= 15mmHg or >= 100mmHg with increase from baseline of >= 15mmHg, low or high pulse: <= 50 beats/min with decrease from baseline of >= 15 beats/min or >= 120 beats/min with increase from baseline of >= 15 beats/min, low or high temperature: <= 36 degree Celsius (deg C) or >= 37.5 deg C. (NCT02928224)
Timeframe: From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks)

Intervention	Participants (Count of Participants)
	Diastolic Blood Pressure - High	Diastolic Blood Pressure - Low	Pulse Rate - High	Pulse Rate - Low	Systolic Blood Pressure - High	Systolic Blood Pressure - Low	Temperature - High	Temperature - Low
Phase 3: Control Arm	7	5	20	3	5	10	25	55
Phase 3: Doublet Arm	6	27	14	4	13	28	23	84
Phase 3: Triplet Arm	8	21	23	3	19	37	33	93

Phase 3: Number of Participants With Shift in Visual Acuity Logarithm of the Minimum Angle of Resolution (LogMAR) Score

Visual acuity was measured using the Snellen visual acuity conversion chart. This was determined by establishing the smallest optotypes that could be identified correctly by the participant at a given observation distance. Snellen visual acuity was reported as a Snellen fraction (m/M) in which the numerator (m) indicated the test distance and the denominator (M) indicated the distance at which the gap of the equivalent Landolt ring subtends 1 minute of arc. The LogMAR score was calculated as - log(m/M). The maximum increase in score of <= 0, 0 to < 0.1, 0.1 to < 0.2, 0.2 to < 0.3 and >=0.3 relative to baseline in LogMAR were reported in this endpoint. (NCT02928224)
Timeframe: From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks)

Intervention	Participants (Count of Participants)
	Baseline <=0 to >0-<0.1	Baseline <=0 to 0.1-<0.2	Baseline <=0 to 0.2-<0.3	Baseline <=0 to >=0.3	Baseline <=0 to missing score	Baseline >0-<0.1 to <=0	Baseline >0-<0.1 to 0.1-<0.2	Baseline >0-<0.1 to 0.2-<0.3	Baseline >0-<0.1 to >=0.3	Baseline >0-<0.1 to missing score	Baseline 0.1-<0.2 to <=0	Baseline 0.1-<0.2 to >0-<0.1	Baseline 0.2-<0.3 to <=0	Baseline 0.2-<0.3 to >0-<0.1	Baseline 0.2-<0.3 to 0.1-<0.2	Baseline 0.2-<0.3 to missing score	Baseline >=0.3 to <=0	Baseline >=0.3 to >0-<0.1	Baseline >=0.3 to 0.1-<0.2	Baseline >=0.3 to 0.2-<0.3	Baseline >=0.3 to missing score	Baseline 0.1-<0.2 to 0.2-<0.3	Baseline 0.1-<0.2 to missing score
Phase 3: Control Arm	0	0	0	0	129	0	0	0	0	30	0	0	0	0	0	5	0	0	0	0	13	0	7
Phase 3: Doublet Arm	8	3	0	1	86	6	2	1	0	25	1	0	0	0	1	4	2	0	1	0	19	3	9
Phase 3: Triplet Arm	33	15	4	6	9	17	7	4	3	3	5	1	1	3	3	1	9	4	1	2	1	0	0

Phase 3: Number of Participants With Shifts in Left Ventricular Ejection Fraction (LVEF) From Baseline to Maximum Grade On-treatment

Left ventricular ejection fraction (LVEF) abnormalities were defined according to CTCAE version 4.03 where Grade 0: Non-missing value below Grade 2, Grade 2: LVEF between 40% and 50% or absolute change from baseline between -10% and < -20%, Grade 3: LVEF between 20% and 39% or absolute change from baseline <= -20%, Grade 4: LVEF lower than 20%. Categories with at least 1 non-zero data values showing any shift in Grade from baseline to 1 day after dose 1 (post-baseline) were reported. Participants whose grade category was unchanged (e.g. Grade 0 to Grade 0) were not reported. (NCT02928224)
Timeframe: From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks)

Intervention	Participants (Count of Participants)
	Baseline Grade 0 to Grade 2 post baseline	Baseline Grade 0 to Grade 3 post baseline	Baseline Grade 0 to missing grade	Baseline Grade 2 to missing grade	Baseline missing grade to Grade 0 post baseline
Phase 3: Control Arm	0	0	186	2	0
Phase 3: Doublet Arm	0	1	205	3	0
Phase 3: Triplet Arm	27	1	17	0	1

Reviews

3 reviews available for carbamates and Metastase

Article	Year
Binimetinib, encorafenib and cetuximab (BEACON Trial) combination therapy for patients with BRAF V600E-mutant metastatic colorectal cancer. Drugs of today (Barcelona, Spain : 1998), 2019, Volume: 55, Issue:11 Topics: Benzimidazoles; Carbamates; Cetuximab; Clinical Trials, Phase III as Topic; Colorectal Neoplasms; Dr	2019
Encorafenib: A Review in Metastatic Colorectal Cancer with a BRAF V600E Mutation. Drugs, 2021, Volume: 81, Issue:7 Topics: Antineoplastic Combined Chemotherapy Protocols; Carbamates; Cetuximab; Colorectal Neoplasms; Drug In	2021
Encorafenib and Binimetinib: First Global Approvals. Drugs, 2018, Volume: 78, Issue:12 Topics: Benzimidazoles; Carbamates; Drug Approval; Humans; MAP Kinase Kinase Kinases; Melanoma; Molecular St	2018

Trials

3 trials available for carbamates and Metastase

Article	Year
Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2021, 02-01, Volume: 39, Issue:4 Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carbamates; Cetuxima	2021
A phase II study of CI-980 in previously untreated extensive small cell lung cancer: an Ohio State University phase II research consortium study. Cancer investigation, 2002, Volume: 20, Issue:2 Topics: Adult; Aged; Antineoplastic Agents; Carbamates; Carcinoma, Small Cell; Female; Humans; Leukocyte Cou	2002
Clinical trial of acetylenic carbamate: 1,1-diphenyl-2-propynyl cyclohexanecarbamate (NSC-112682). Cancer chemotherapy reports, 1970, Volume: 54, Issue:3 Topics: Adolescent; Adult; Aged; Alkynes; Antineoplastic Agents; Carbamates; Carcinoma, Bronchogenic; Carcin	1970

Other Studies

19 other studies available for carbamates and Metastase

Article	Year
Intracranial antitumor activity with encorafenib plus binimetinib in patients with melanoma brain metastases: A case series. Cancer, 2020, 02-01, Volume: 126, Issue:3 Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Brain Neoplasms; Carbamates;	2020
Complete response with combined BRAF and MEK inhibition in BRAF mutated advanced low-grade serous ovarian carcinoma. Upsala journal of medical sciences, 2020, Volume: 125, Issue:4 Topics: Antineoplastic Agents; Benzimidazoles; Bevacizumab; CA-125 Antigen; Carbamates; Carboplatin; Cystade	2020
Evaluation of the Cost-effectiveness of Doublet Therapy in Metastatic BRAF Variant Colorectal Cancer. JAMA network open, 2021, 01-04, Volume: 4, Issue:1 Topics: Antineoplastic Combined Chemotherapy Protocols; Carbamates; Cetuximab; Colorectal Neoplasms; Cost-Be	2021
Norcyanine-Carbamates Are Versatile Near-Infrared Fluorogenic Probes. Journal of the American Chemical Society, 2021, 04-21, Volume: 143, Issue:15 Topics: Animals; Carbamates; Carbocyanines; Cell Line, Tumor; Disease Models, Animal; Female; Fluorescence R	2021
PD-L1 status does not predict the outcome of BRAF inhibitor therapy in metastatic melanoma. European journal of cancer (Oxford, England : 1990), 2018, Volume: 88 Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Carba	2018
Eruptive naevi in a patient treated with LGX818 for BRAF mutant metastatic melanoma. Melanoma research, 2015, Volume: 25, Issue:1 Topics: Antineoplastic Agents; Carbamates; Dermatology; Dermoscopy; Humans; Male; Melanoma; Middle Aged; Mut	2015
Notch signaling and ERK activation are important for the osteomimetic properties of prostate cancer bone metastatic cell lines. The Journal of biological chemistry, 2004, Jan-30, Volume: 279, Issue:5 Topics: Basic Helix-Loop-Helix Transcription Factors; Blotting, Western; Bone Neoplasms; Calcium; Carbamates	2004
[Results of the clinical study of a preparation of diiodobenzotef in malignant tumors]. Klinicheskaia meditsina, 1975, Volume: 52, Issue:5 Topics: Adult; Aged; Antineoplastic Agents; Aziridines; Azirines; Benzamides; Breast Neoplasms; Carbamates;	1975
R17934-NSC 238159: a new antitumor drug--I. Effect on experimental tumors and factors influencing effectiveness. European journal of cancer, 1975, Volume: 11, Issue:9 Topics: Animals; Antineoplastic Agents; Benzimidazoles; Carbamates; Ependymoma; Leukemia L1210; Leukemia, Ex	1975
[Growth and metastasis of Lewis' lung carcinoma in mice under the pharmacological action on metabolism and the effects of kinins]. Biulleten' eksperimental'noi biologii i meditsiny, 1987, Volume: 104, Issue:7 Topics: Animals; Carbamates; Cellulose; Dimercaprol; Drug Evaluation, Preclinical; Female; Kinins; Lung Neop	1987
Stage D prostatic carcinoma. Survival rate in relapsed patients following new forms of palliation. Urology, 1974, Volume: 4, Issue:3 Topics: Adrenalectomy; Carbamates; Estranes; Humans; Hypophysectomy; Male; Neoplasm Metastasis; Nitrogen Mus	1974
[Preliminary results of 10 patients with advanced prostatic neoplasm treated with estracyt]. Acta urologica Belgica, 1974, Volume: 42, Issue:3 Topics: Aged; Antineoplastic Agents; Bone Neoplasms; Carbamates; Estranes; Humans; Injections, Intravenous;	1974
Estracyt in hormone-resistant prostatic carcinoma. International urology and nephrology, 1974, Volume: 6, Issue:2 Topics: Adult; Aged; Carbamates; Carcinoma; Drug Evaluation; Drug Resistance; Estranes; Follow-Up Studies; H	1974
Recent data on the mechanism of action of oestrogens in the treatment of prostatic tumour patients. International urology and nephrology, 1974, Volume: 5, Issue:3 Topics: Aged; Antineoplastic Agents; Bone Neoplasms; Carbamates; Castration; Estranes; Humans; Iodine Radioi	1974
Pharmacoclinical study of oral estramustine phosphate (Estracyt) in advanced carcinoma of the prostate. Investigative urology, 1974, Volume: 12, Issue:1 Topics: Acid Phosphatase; Administration, Oral; Antineoplastic Agents; Carbamates; Carcinoembryonic Antigen;	1974
Regional perfusion and circulation-stop method for chemotherapy of cancer and metastasis. Gan, 1974, Volume: 65, Issue:3 Topics: Animals; Antineoplastic Agents; Azirines; Carbamates; Chemotherapy, Cancer, Regional Perfusion; Chym	1974
Treatment of rapidly progressing prostatic carcinoma with estracyt. The Journal of urology, 1972, Volume: 108, Issue:2 Topics: Aged; Antineoplastic Agents; Carbamates; Estranes; Estrogens; Humans; Male; Middle Aged; Neoplasm Me	1972
"Estracyt". British journal of urology, 1971, Volume: 43, Issue:6 Topics: Carbamates; Estradiol; Humans; Male; Neoplasm Metastasis; Nitrogen Mustard Compounds; Prostatic Neop	1971
Mouse mammary carcinogenesis by ethyl and butyl carbamates. Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.), 1969, Volume: 132, Issue:2 Topics: Animals; Carbamates; Female; Injections, Intraperitoneal; Lung Neoplasms; Mammary Neoplasms, Experim	1969