Trial Outcomes & Findings for BRAF Inhibitor, LGX818, Utilizing a Pulsatile Schedule in Patients With Stage IV or Unresectable Stage III Melanoma Characterized by a BRAFV600 Mutation (NCT NCT01894672)

Last Updated: 2024-07-16

Results Overview

Efficacy for all patients will be evaluated by the study sites using RECIST v1.1 and response criteria based on contrast-enhanced CT. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Progression must also involve an increase in size of measurable lesions by at least 5 mm, to minimize the possibility that small changes in a small number of target lesions is falsely interpreted as progression.Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

7 participants

Primary outcome timeframe

1.5 years

Results posted on

2024-07-16

Participant Flow

Protocol Open to Accrual 07/03/2013 Protocol Closed to Accrual 03/24/2015 Primary Completion Date 03/17/2016 Recruitment Location is the medical clinic

Participant milestones

Participant milestones
Measure	LGX818 Patients With Stage IV or Unresectable Stage III Melanoma Characterized by a BRAFV600 Mutation will receive LGX818 capsules orally on a once -daily schedule (QD) dosing at a dose of 300 mg/day, 2 weeks on followed by a 2 week break. This schedule of 2 weeks on, followed by 2 weeks off, will continue for the duration of time the patients remains on the clinical trial. After the follow up visit patients will be contacted approximately every 12 weeks until they have received a subsequent therapy or until they have been off treatment for a year to monitor their survival.
Overall Study STARTED	7
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

BRAF Inhibitor, LGX818, Utilizing a Pulsatile Schedule in Patients With Stage IV or Unresectable Stage III Melanoma Characterized by a BRAFV600 Mutation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LGX818 n=7 Participants Patients With Stage IV or Unresectable Stage III Melanoma Characterized by a BRAFV600 Mutation will receive LGX818 capsules orally on a once -daily schedule (QD) dosing at a dose of 300 mg/day, 2 weeks on followed by a 2 week break. This schedule of 2 weeks on, followed by 2 weeks off, will continue for the duration of time the patients remains on the clinical trial. After the follow up visit patients will be contacted approximately every 12 weeks until they have received a subsequent therapy or until they have been off treatment for a year to monitor their survival.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=93 Participants
Age, Categorical >=65 years	3 Participants n=93 Participants
Age, Continuous	58 years n=93 Participants
Sex: Female, Male Female	2 Participants n=93 Participants
Sex: Female, Male Male	5 Participants n=93 Participants
Region of Enrollment United States	7 Participants n=93 Participants

PRIMARY outcome

Timeframe: 1.5 years

Outcome measures

Outcome measures
Measure	LGX818 n=7 Participants Patients With Stage IV or Unresectable Stage III Melanoma Characterized by a BRAFV600 Mutation will receive LGX818 capsules orally on a once -daily schedule (QD) dosing at a dose of 300 mg/day, 2 weeks on followed by a 2 week break. This schedule of 2 weeks on, followed by 2 weeks off, will continue for the duration of time the patients remains on the clinical trial. After the follow up visit patients will be contacted approximately every 12 weeks until they have received a subsequent therapy or until they have been off treatment for a year to monitor their survival.
Number of Participants With Response According to RECIST v1.1 Criteria Stable Disease	2 Participants
Number of Participants With Response According to RECIST v1.1 Criteria Partial Response	2 Participants
Number of Participants With Response According to RECIST v1.1 Criteria Complete Response	2 Participants
Number of Participants With Response According to RECIST v1.1 Criteria Progressive Disease	1 Participants

SECONDARY outcome

Timeframe: 1.5 years

Response rate (defined as complete + partial response) and 95% confidence interval will be estimated.

Outcome measures

Outcome measures
Measure	LGX818 n=7 Participants Patients With Stage IV or Unresectable Stage III Melanoma Characterized by a BRAFV600 Mutation will receive LGX818 capsules orally on a once -daily schedule (QD) dosing at a dose of 300 mg/day, 2 weeks on followed by a 2 week break. This schedule of 2 weeks on, followed by 2 weeks off, will continue for the duration of time the patients remains on the clinical trial. After the follow up visit patients will be contacted approximately every 12 weeks until they have received a subsequent therapy or until they have been off treatment for a year to monitor their survival.
Response Rate	57 percentage of participants Interval 20.0 to 94.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 1.5 years

Overall survival will be calculated for the start of treatment to the date of last death or follow-up.

Outcome measures

Outcome measures
Measure	LGX818 n=7 Participants Patients With Stage IV or Unresectable Stage III Melanoma Characterized by a BRAFV600 Mutation will receive LGX818 capsules orally on a once -daily schedule (QD) dosing at a dose of 300 mg/day, 2 weeks on followed by a 2 week break. This schedule of 2 weeks on, followed by 2 weeks off, will continue for the duration of time the patients remains on the clinical trial. After the follow up visit patients will be contacted approximately every 12 weeks until they have received a subsequent therapy or until they have been off treatment for a year to monitor their survival.
Overall Survival Alive	2 Participants
Overall Survival Dead	5 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Cycle 1 - Day 1, 15; Cycle 2 - Day 15; Cycle 3 - Day 1, Day 15

Population: Data were not collected

PK parameters will be determined on PK profiles after the first dose and at steady-state using non-compartmental method(s) using WinNonlin

Outcome measures

Outcome data not reported

Adverse Events

LGX818

Serious events: 6 serious events

Other events: 7 other events

Deaths: 5 deaths

Serious adverse events

Serious adverse events
Measure	LGX818 n=7 participants at risk Patients With Stage IV or Unresectable Stage III Melanoma Characterized by a BRAFV600 Mutation will receive LGX818 capsules orally on a once -daily schedule (QD) dosing at a dose of 300 mg/day, 2 weeks on followed by a 2 week break. This schedule of 2 weeks on, followed by 2 weeks off, will continue for the duration of time the patients remains on the clinical trial. After the follow up visit patients will be contacted approximately every 12 weeks until they have received a subsequent therapy or until they have been off treatment for a year to monitor their survival.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Treatment related secondary malignancy	42.9% 3/7 • Number of events 3
Respiratory, thoracic and mediastinal disorders Pleural effusion	14.3% 1/7 • Number of events 1
Nervous system disorders Facial muscle weakness	14.3% 1/7 • Number of events 1
Musculoskeletal and connective tissue disorders Back pain	14.3% 1/7 • Number of events 1
Skin and subcutaneous tissue disorders Skin & subcutaneous tissue disorders Other, spec	14.3% 1/7 • Number of events 1

Other adverse events

Other adverse events
Measure	LGX818 n=7 participants at risk Patients With Stage IV or Unresectable Stage III Melanoma Characterized by a BRAFV600 Mutation will receive LGX818 capsules orally on a once -daily schedule (QD) dosing at a dose of 300 mg/day, 2 weeks on followed by a 2 week break. This schedule of 2 weeks on, followed by 2 weeks off, will continue for the duration of time the patients remains on the clinical trial. After the follow up visit patients will be contacted approximately every 12 weeks until they have received a subsequent therapy or until they have been off treatment for a year to monitor their survival.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	85.7% 6/7
Musculoskeletal and connective tissue disorders Arthralgia/myalgia	85.7% 6/7
Skin and subcutaneous tissue disorders Hyperkeratosis	42.9% 3/7
Gastrointestinal disorders Nausea	42.9% 3/7
Skin and subcutaneous tissue disorders Pruritus	28.6% 2/7
Skin and subcutaneous tissue disorders Rash	28.6% 2/7
General disorders Fatigue	14.3% 1/7
Nervous system disorders Dysgeusia	14.3% 1/7
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cutaneous squamous cell carcinoma	28.6% 2/7
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Keratoacanthoma	14.3% 1/7
Nervous system disorders Bell's Palsy	14.3% 1/7

Additional Information

Dr. Paul Chapman MD

Memorial Sloan Kettering Cancer Center

Phone: 646-888-4162

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place