NCT01436656

A Phase I Study of Oral LGX818 in Adult Patients With Advanced or Metastatic BRAF Mutant Melanoma

Completed Phase 1 Results posted Last updated 28 October 2024

What this trial tests

Phase 1 trial testing LGX818 in Melanoma and Metastatic Colorectal Cancer in 107 participants. Completed in 7 November 2022.

Timeline

5 September 2011

Primary endpoint
1 October 2012

7 November 2022

Quick facts

Lead sponsor	Pfizer
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	107
Start date	5 September 2011
Primary completion	1 October 2012
Estimated completion	7 November 2022
Sites	24 locations across France, Japan, Norway, Switzerland, Australia, United States, Spain

Drugs / interventions tested

• LGX818 (lgx818) — full drug profile →

Conditions studied

• Melanoma and Metastatic Colorectal Cancer — all drugs for Melanoma and Metastatic Colorectal Cancer →

Sponsor

Pfizer — full company profile →

Who can join

18 and older, any sex, with Melanoma and Metastatic Colorectal Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Dose-Limiting Toxicity (DLT) During Dose Escalation Phase Primary · Up to 28 days

DLT= Adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within first 28 days of treatment with encorafenib and met any of following criteria: \>=grade (G)3 neutropenia or thrombocytopenia for \>7 days; G4 thrombocytopenia; febrile neutropenia; \>=G3 serum creatinine, blood bilirubin; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) and lipase and/or serum amylase (\>=G3 for \> 7 consecutive days or G4); \>=G3 ALT or AST and \>=G2 blood bilirubin; \>=G3 persisten

Group	Value	95% CI
50 mg Encorafenib QD	0
100 mg Encorafenib QD	1
150 mg Encorafenib QD	0
75 mg Encorafenib BID	0
200 mg Encorafenib QD	0
100 mg Encorafenib BID	1
300 mg Encorafenib QD	1
150 mg Encorafenib BID	1
450 mg Encorafenib QD	0
550 mg Encorafenib QD	1
700 mg Encorafenib QD	2

Number of Participants With DLT During Dose Expansion Phase Primary · Up to 28 days

DLT= Adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within first 28 days of treatment with encorafenib and met any of following criteria: \>=grade (G)3 neutropenia or thrombocytopenia for \>7 days; G4 thrombocytopenia; febrile neutropenia; \>=G3 serum creatinine, blood bilirubin; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) and lipase and/or serum amylase (\>=G3 for \> 7 consecutive days or G4); \>=G3 ALT or AST and \>=G2 blood bilirubin; \>=G3 persisten

Group	Value	95% CI
Mel Naive 300 mg Encorafenib	2
Mel Naive 450 mg Encorafenib	2
Mel Pre-treated: 300 mg Encorafenib	0
Mel Pre-treated: 450 mg Encorafenib	4
Mel Stepwise: 450 mg Encorafenib	1
Metastatic Colorectal Cancer: 300 mg Encorafenib	0
Metastatic Colorectal Cancer: 450 mg Encorafenib	3

Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Dose Escalation Phase Secondary · From start of study treatment until 30 days after last dose of study treatment (maximum of 556.1 weeks of treatment exposure)

An AE was defined as the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions. An SAE was defined as one of the following: fatal or life-threatening; resulted in significant disability/incapacity; congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization unless for routine treatment, elective or pre-planned treatment for a pre-existing condition, treatment on an emergency outpatient basis, social reasons and respite care in the absence of any deterioration in the part

Adverse Events (AEs)

Group	Value	95% CI
50 mg Encorafenib QD	4
100 mg Encorafenib QD	10
150 mg Encorafenib QD	6
75 mg Encorafenib BID	3
200 mg Encorafenib QD	4
100 mg Encorafenib BID	5
300 mg Encorafenib QD	5
150 mg Encorafenib BID	4
450 mg Encorafenib QD	6
550 mg Encorafenib QD	5
700 mg Encorafenib QD	2

Serious Adverse Events (SAEs)

Group	Value	95% CI
50 mg Encorafenib QD	3
100 mg Encorafenib QD	7
150 mg Encorafenib QD	3
75 mg Encorafenib BID	2
200 mg Encorafenib QD	4
100 mg Encorafenib BID	2
300 mg Encorafenib QD	4
150 mg Encorafenib BID	2
450 mg Encorafenib QD	2
550 mg Encorafenib QD	3
700 mg Encorafenib QD	1

Number of Participants With AEs and SAEs During Dose Expansion Phase Secondary · From start of study treatment until 30 days after last dose of study treatment (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)

An AE was defined as the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions. An SAE was defined as one of the following: fatal or life-threatening; resulted in significant disability/incapacity; congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization unless for routine treatment, elective or pre-planned treatment for a pre-existing condition, treatment on an emergency outpatient basis, social reasons and respite care in the absence of any deterioration in the part

Adverse Events (AEs)

Group	Value	95% CI
Mel Naive 300 mg Encorafenib	9
Mel Naive 450 mg Encorafenib	6
Mel Pre-treated: 300 mg Encorafenib	2
Mel Pre-treated: 450 mg Encorafenib	16
Mel Stepwise: 450 mg Encorafenib	2
Metastatic Colorectal Cancer: 300 mg Encorafenib	6
Metastatic Colorectal Cancer: 450 mg Encorafenib	12

Serious Adverse Events (SAEs)

Group	Value	95% CI
Mel Naive 300 mg Encorafenib	2
Mel Naive 450 mg Encorafenib	4
Mel Pre-treated: 300 mg Encorafenib	2
Mel Pre-treated: 450 mg Encorafenib	9
Mel Stepwise: 450 mg Encorafenib	2
Metastatic Colorectal Cancer: 300 mg Encorafenib	3
Metastatic Colorectal Cancer: 450 mg Encorafenib	6

Progression Free Survival (PFS): Dose Escalation Phase Secondary · From start of study treatment until first documentation of PD or death due to any cause or censoring date (maximum of 556.1 weeks of treatment exposure)

PFS was defined as time from date of first study treatment intake to date of first documented disease progression (PD) or death due to any cause. If a participant did not have an event, data censoring was done at the date of last adequate tumor assessment. PD was defined for target disease as at least a 20% increase in sum of longest diameters of all measured target lesions, taking as reference smallest sum on study (this included baseline sum if that was smallest on study), sum also demonstrated absolute increase of greater than or equal to (\>=) 5 mm, or appearance of \>=1 new lesions. For n

Group	Value	95% CI
50 mg Encorafenib QD	75.0	19.4 – 99.4
100 mg Encorafenib QD	10.0	0.3 – 44.5
150 mg Encorafenib QD	50.0	11.8 – 88.2
75 mg Encorafenib BID	33.3	0.8 – 90.6
200 mg Encorafenib QD	50.0	6.8 – 93.2
100 mg Encorafenib BID	40.0	5.3 – 85.3
300 mg Encorafenib QD	0.0	0.0 – 52.2
150 mg Encorafenib BID	75.0	19.4 – 99.4
450 mg Encorafenib QD	33.3	4.3 – 77.7
550 mg Encorafenib QD	20.0	0.5 – 71.6
700 mg Encorafenib QD	0.0	0.0 – 84.2

PFS: Dose Expansion Phase Secondary · From start of study treatment until first documentation of PD or death due to any cause or censoring date (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)

PFS was defined as time from date of first study treatment intake to date of first documented PD or death due to any cause. If a participant did not have an event, data censoring was done at the date of last adequate tumor assessment. PD was defined for target disease as at least a 20% increase in sum of longest diameters of all measured target lesions, taking as reference smallest sum on study (this included baseline sum if that was smallest on study), sum also demonstrated absolute increase of \>= 5 mm, or appearance of \>=1 new lesions. For non-target disease: PD was defined as unequivocal

Group	Value	95% CI
Mel Naive 300 mg Encorafenib	16.5	7.4 – NA
Mel Naive 450 mg Encorafenib	19.3	7.4 – NA
Mel Pre-treated: 300 mg Encorafenib	0.6	0.6 – NA
Mel Pre-treated: 450 mg Encorafenib	2.0	1.6 – 3.7
Mel Stepwise: 450 mg Encorafenib	20.1	10.9 – NA
Metastatic Colorectal Cancer: 300 mg Encorafenib	4.5	2.3 – 7.2
Metastatic Colorectal Cancer: 450 mg Encorafenib	4.0	1.8 – 5.5

Duration of Response (DOR): Dose Escalation Phase Secondary · From first observation of response until first time of PD or death due to any cause (Maximum of 556.1 weeks of treatment exposure)

DOR was defined as the time from first observation of response CR or partial response \[PR\]) to the first time of progression or death. CR was defined as complete disappearance of all target and non-target lesions, and sustained for at least 4 weeks apart before progression. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. For target disease, PD=at least a 20% increase in sum of

Group	Value	95% CI
50 mg Encorafenib QD	NA	NA – NA
100 mg Encorafenib QD	NA	NA – NA
150 mg Encorafenib QD	NA	NA – NA
75 mg Encorafenib BID	NA	NA – NA
200 mg Encorafenib QD	NA	NA – NA
100 mg Encorafenib BID	NA	NA – NA
150 mg Encorafenib BID	NA	NA – NA
450 mg Encorafenib QD	NA	NA – NA
550 mg Encorafenib QD	NA	NA – NA

Time to Response (TTR): Dose Escalation Phase Secondary · From date of start of treatment until CR or PR or censoring date (maximum of 556.1 weeks of treatment exposure)

TTR was defined as the time from date of treatment until first documented response (CR or PR). CR was defined as complete disappearance of all target and non-target lesions sustained for at least 4 weeks apart before progression. Any pathological lymph nodes (whether target or non-target) reduced in short axis to \<10 mm. PR was defined as at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants who did not achieve a confirmed PR or CR, were censored at last adequate tumor assessment date when they did not progress (including dea

Participant 1

Group	Value	95% CI
50 mg Encorafenib QD	57

Participant 2

Group	Value	95% CI
50 mg Encorafenib QD	952

Participant 3

Group	Value	95% CI
50 mg Encorafenib QD	22

Participant 4

Group	Value	95% CI
100 mg Encorafenib QD	55

Participant 5

Group	Value	95% CI
150 mg Encorafenib QD	897

Participant 6

Group	Value	95% CI
150 mg Encorafenib QD	21

Participant 7

Group	Value	95% CI
150 mg Encorafenib QD	72

Participant 8

Group	Value	95% CI
200 mg Encorafenib QD	27

DOR: Dose Expansion Phase Secondary · From first observation of response until first time of PD or death due to any cause (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)

DOR was defined as the time from first observation of response (CR or PR\] to the first time of progression or death. CR was defined as complete disappearance of all target and non-target lesions and sustained for at least 4 weeks apart before progression. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to (\<10 mm. PR defined as at least 30 percent (%) decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. For target disease, PD=at least a 20% increase in sum of longest diameters of all measured target lesi

Group	Value	95% CI
Mel Naive 300 mg Encorafenib	NA	NA – NA
Mel Naive 450 mg Encorafenib	NA	NA – NA
Mel Pre-treated: 450 mg Encorafenib	NA	NA – NA
Mel Stepwise: 450 mg Encorafenib	NA	NA – NA
Metastatic Colorectal Cancer: 300 mg Encorafenib	NA	NA – NA

TTR: Dose Expansion Phase Secondary · From date of start of treatment until CR or PR or censoring date (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)

TTR was defined as the time from date of treatment until first documented response (CR or PR). CR was defined as complete disappearance of all target and non-target lesions sustained for at least 4 weeks apart before progression. Any pathological lymph nodes (whether target or non-target) reduced in short axis to \<10 mm. PR was defined as at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants who did not achieve a confirmed PR or CR, were censored at last adequate tumor assessment date when they did not progress (including dea

Participant 1

Group	Value	95% CI
Mel Naive 300 mg Encorafenib	211

Participant 2

Group	Value	95% CI
Mel Naive 300 mg Encorafenib	22

Participant 3

Group	Value	95% CI
Mel Naive 300 mg Encorafenib	23

Participant 4

Group	Value	95% CI
Mel Naive 300 mg Encorafenib	22

Participant 5

Group	Value	95% CI
Mel Naive 300 mg Encorafenib	56

Participant 6

Group	Value	95% CI
Mel Naive 300 mg Encorafenib	23

Participant 7

Group	Value	95% CI
Mel Naive 300 mg Encorafenib	56

Participant 8

Group	Value	95% CI
Mel Naive 450 mg Encorafenib	78

Overall Survival (OS): Dose Expansion Phase Secondary · From start of study treatment until date of death or censoring date (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)

Overall survival was defined as the time from the date of first study treatment to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method.

Group	Value	95% CI
Mel Naive 300 mg Encorafenib	NA	11.6 – NA
Mel Naive 450 mg Encorafenib	12.5	7.7 – NA
Mel Pre-treated: 300 mg Encorafenib	NA	2.4 – NA
Mel Pre-treated: 450 mg Encorafenib	9.5	3.7 – 13.2
Mel Stepwise: 450 mg Encorafenib	NA	30.7 – NA
Metastatic Colorectal Cancer: 300 mg Encorafenib	7.2	5.6 – 10.5
Metastatic Colorectal Cancer: 450 mg Encorafenib	8.0	4.0 – NA

Maximum Observed Plasma Concentration of LGX818: Dose Escalation Phase Secondary · Pre-dose (0 hour), 0.5, 3, 4, 6, 8, 10 (only for BID arms), 24 hours post dose on Day 1 and 15 of Cycle 1 (each cycle=28 days)

Cycle 1 Day 1

Group	Value	95% CI
50 mg Encorafenib QD (Capsules)	970	± NA
50 mg Encorafenib QD (Microemulsion)	846	± 82.92
100 mg Encorafenib QD (Capsules)	1630	± 42.36
100 mg Encorafenib QD (Microemulsion)	1020	± 49.06
150 mg Encorafenib QD	1570	± 28.82
75 mg Encorafenib BID	733	± 46.32
200 mg Encorafenib QD	1850	± 28.06
100 mg of Encorafenib BID (Microemulsion)	1200	± 28.06
300 mg Encorafenib QD	3310	± 42.54
150 mg Encorafenib BID	2510	± 58.15
450 mg Encorafenib QD	5970	± 56.35
550 mg Encorafenib QD	5360	± 36.87

Cycle 1 Day 15

Group	Value	95% CI
50 mg Encorafenib QD (Capsules)	465	± NA
50 mg Encorafenib QD (Microemulsion)	334	± 57.7
100 mg Encorafenib QD (Capsules)	959	± 25.19
100 mg Encorafenib QD (Microemulsion)	949	± 27.4
150 mg Encorafenib QD	1300	± 29.08
75 mg Encorafenib BID	NA	± NA
200 mg Encorafenib QD	1300	± 1220
100 mg of Encorafenib BID (Microemulsion)	NA	± NA
300 mg Encorafenib QD	2920	± 34.41
150 mg Encorafenib BID	NA	± NA
450 mg Encorafenib QD	3950	± 49.12
550 mg Encorafenib QD	4170	± 48.94

Adverse events — posted to ClinicalTrials.gov

Time frame: From start of study treatment until 30 days after last dose of study treatment (maximum of 556.1 weeks of treatment exposure) for Dose escalation arms and (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively) for Dose expansion arms.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dose Escalation: 50 mg Encorafenib QD

Serious: 3/4 (75%)

Deaths: 1/4

Dose Escalation: 100 mg Encorafenib QD

Serious: 7/10 (70%)

Deaths: 3/10

Dose Escalation:150 mg Encorafenib QD

Serious: 3/6 (50%)

Deaths: 1/6

Dose Escalation: 75 mg Encorafenib BID

Serious: 2/3 (67%)

Deaths: 0/3

Dose Escalation: 200 mg Encorafenib QD

Serious: 4/4 (100%)

Deaths: 1/4

Dose Escalation: 100 mg Encorafenib BID

Serious: 2/5 (40%)

Deaths: 1/5

Dose Escalation: 300 mg Encorafenib QD

Serious: 4/5 (80%)

Deaths: 2/5

Dose Escalation: 150 mg Encorafenib BID

Serious: 2/4 (50%)

Deaths: 1/4

Dose Escalation: 450 mg Encorafenib QD

Serious: 2/6 (33%)

Deaths: 1/6

Dose Escalation: 550 mg Encorafenib QD

Serious: 3/5 (60%)

Deaths: 0/5

Dose Escalation: 700 mg Encorafenib QD

Serious: 1/2 (50%)

Deaths: 0/2

Dose Expansion: Mel Naive 300 mg Encorafenib

Serious: 2/9 (22%)

Deaths: 2/9

Dose Expansion: Mel Naive 450 mg Encorafenib

Serious: 4/6 (67%)

Deaths: 3/6

Dose Expansion: Mel Pre-treated 300 mg Encorafenib

Serious: 2/2 (100%)

Deaths: 1/2

Dose Expansion: Mel Pre-treated 450 mg Encorafenib

Serious: 9/16 (56%)

Deaths: 11/16

Dose Expansion: Mel Stepwise 450 mg Encorafenib

Serious: 2/2 (100%)

Deaths: 1/2

Dose Expansion: Metastatic Colorectal Cancer 300 mg Encorafenib

Serious: 3/6 (50%)

Deaths: 5/6

Dose Expansion: Metastatic Colorectal Cancer 450 mg Encorafenib

Serious: 6/12 (50%)

Deaths: 8/12

Serious adverse events (82 terms)

Reaction	System	Dose Escalation: 50 mg Enc…	Dose Escalation: 100 mg En…	Dose Escalation:150 mg Enc…	Dose Escalation: 75 mg Enc…	Dose Escalation: 200 mg En…	Dose Escalation: 100 mg En…	Dose Escalation: 300 mg En…	Dose Escalation: 150 mg En…	Dose Escalation: 450 mg En…	Dose Escalation: 550 mg En…	Dose Escalation: 700 mg En…	Dose Expansion: Mel Naive …	Dose Expansion: Mel Naive …	Dose Expansion: Mel Pre-tr…	Dose Expansion: Mel Pre-tr…	Dose Expansion: Mel Stepwi…	Dose Expansion: Metastatic…	Dose Expansion: Metastatic…
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Intracranial pressure increased	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Intestinal obstruction	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Visual impairment	Eye disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dysphagia	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Ileus	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Inguinal hernia	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Subileus	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
General physical health deterioration	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Multi-organ failure	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hepatic pain	Hepatobiliary disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Sarcoidosis	Immune system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Brain herniation	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

Other adverse events (94 terms — click to expand)

Reaction	System	Dose Escalation: 50 mg Enc…	Dose Escalation: 100 mg En…	Dose Escalation:150 mg Enc…	Dose Escalation: 75 mg Enc…	Dose Escalation: 200 mg En…	Dose Escalation: 100 mg En…	Dose Escalation: 300 mg En…	Dose Escalation: 150 mg En…	Dose Escalation: 450 mg En…	Dose Escalation: 550 mg En…	Dose Escalation: 700 mg En…	Dose Expansion: Mel Naive …	Dose Expansion: Mel Naive …	Dose Expansion: Mel Pre-tr…	Dose Expansion: Mel Pre-tr…	Dose Expansion: Mel Stepwi…	Dose Expansion: Metastatic…	Dose Expansion: Metastatic…
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Keratosis pilaris	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hyperkeratosis	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Xerosis	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Weight decreased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Melanocytic naevus	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Erythema	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dysgeusia	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dermal cyst	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hair texture abnormal	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Papule	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pruritus generalised	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Lymphopenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Keratosis follicular	Congenital, familial and genetic disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dry mouth	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Chills	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

Most-reported serious reactions: Nausea, Vomiting, Asthenia, Fatigue, Arthralgia, Back pain, Intracranial pressure increased, Intestinal obstruction.

Data from ClinicalTrials.gov NCT01436656 adverse events section.

Sponsor's own description

CLGX818X2101 is a first-time in-human, phase I study to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of daily administered LGX818 (daily, twice daily and/or every-other-day), a RAF kinase inhibitor. Patients with locally advanced or metastatic melanoma harboring the BRAF V600 mutation (during dose escalation phase and expansion phase) and patients with metastatic colorectal cancer harboring the BRAF V600 mutation (during the expansion phase) will be enrolled. The study consists of a dose escalation part were cohorts of patients will receive escalating oral doses of LGX818, followed by a safety dose expansion part were patients will be treated with oral dose of LGX818 given at the MTD or RP2D.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. The role of BRAF V600 mutation in melanoma.
   Ascierto PA, Kirkwood JM, Grob JJ, Simeone E, et al · · 2012 · cited 534× · PMID 22554099 · DOI 10.1186/1479-5876-10-85
2. Melanoma treatment in review.
   Domingues B, Lopes JM, Soares P, Pópulo H. · · 2018 · cited 432× · PMID 29922629 · DOI 10.2147/itt.s134842
3. Targeting the ERK Signaling Pathway in Melanoma.
   Savoia P, Fava P, Casoni F, Cremona O. · · 2019 · cited 137× · PMID 30934534 · DOI 10.3390/ijms20061483
4. Current Advances in the Treatment of BRAF-Mutant Melanoma.
   Patel H, Yacoub N, Mishra R, White A, et al · · 2020 · cited 133× · PMID 32092958 · DOI 10.3390/cancers12020482
5. Dabrafenib and its potential for the treatment of metastatic melanoma.
   Menzies AM, Long GV, Murali R. · · 2012 · cited 108× · PMID 23251089 · DOI 10.2147/dddt.s38998
6. Targeting the RAS oncogene.
   Takashima A, Faller DV. · · 2013 · cited 95× · PMID 23360111 · DOI 10.1517/14728222.2013.764990
7. Receptor tyrosine kinases and downstream pathways as druggable targets for cancer treatment: the current arsenal of inhibitors.
   Montor WR, Salas AROSE, Melo FHM. · · 2018 · cited 80× · PMID 29455659 · DOI 10.1186/s12943-018-0792-2
8. BRAF vs RAS oncogenes: are mutations of the same pathway equal? Differential signalling and therapeutic implications.
   Oikonomou E, Koustas E, Goulielmaki M, Pintzas A. · · 2014 · cited 80× · PMID 25361007 · DOI 10.18632/oncotarget.2555