V600-mutated BRAF Unresectable Melanoma, V600-mutated BRAF Metastatic Melanoma, Stage III or Stage IV Metastatic Melanoma That Has Not Been Previously Treated With a Selective BRAF Inhibitor
Conditions
Brief summary
The purpose of this research study is to test the safety of an investigational new drug called PLX3397 when used in combination with Vemurafenib (Zelboraf™) at different dose levels. Vemurafenib has been approved by the United States Food and Drug Administration (FDA)/European Medicines Agency (EMA) for the treatment of a specific category of unresectable or metastatic melanoma.
Interventions
DRUGPLX3397
DRUGvemurafenib
Sponsors
Plexxikon
Daiichi Sankyo
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female ≥18 years old. * Patients with histologically confirmed unresectable Stage III or Stage IV metastatic melanoma who have not been previously treated with a selective BRAF inhibitor. * Presence of a BRAF V600 mutation in the tumor tissue using the cobas BRAF mutation assay or comparable standard of care methodology. * Measurable disease per RECIST v. 1.1 criteria. * ECOG performance status 0 or 1.
Exclusion criteria
* Radiation therapy within 14 days of C1D1. * Investigational drug use within 28 days of C1D1. * Patients with active CNS lesions are excluded (i.e., those with radiographically unstable, symptomatic lesions). However, patients treated with stereotactic therapy or surgery are eligible if they remain without evidence of disease progression in the brain for ≥3 weeks.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma | 1 year |
Countries
France, Germany, United States
Participant flow
Recruitment details
A total of 13 participants who met all inclusion and none of the exclusion criteria were enrolled in the study.
Pre-assignment details
This was an open-label, multicenter, Phase 1b, dose-escalation study, followed by an Extension Phase at the recommended Phase 2 dose (RP2D) of both drugs. During Dose-escalation (planned n=40), cohorts of 3 to 6 participants were enrolled to identify the RP2D of each agent to be administered to patients enrolled in the subsequent Extension Phase.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID Participant who received 800 mg/day (400 twice daily \[BID\]) of PLX3397 and 720 mg BID of vemurafenib. | 4 |
| Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID Participants who received 800 mg/day (400 twice daily \[BID\]) of PLX3397 and 960 mg BID of vemurafenib. | 9 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | 2 active cancers | 0 | 1 |
| Overall Study | Adverse Event | 1 | 3 |
| Overall Study | Disease progression | 2 | 4 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID | Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID | Total |
|---|---|---|---|
| Age, Continuous | 42 years | 60.1 years | 54.5 years |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 9 |
| other Total, other adverse events | 4 / 4 | 9 / 9 |
| serious Total, serious adverse events | 0 / 4 | 4 / 9 |
Outcome results
Primary
Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma
Time frame: 1 year
Population: Adverse events (AEs) were assessed in the modified intent-to-treat population (mITT).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID | Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma | Any primary system organ class | 100 percentage of participants |
| Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID | Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma | Any AE | 100 percentage of participants |
| Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID | Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma | AEs related to both PLX3397 and vemurafenib | 100 percentage of participants |
| Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID | Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma | AEs related to PLX3397 | 75 percentage of participants |
| Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID | Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma | AEs related vemurafenib | 25 percentage of participants |
| Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID | Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma | AEs leading to withdrawal from any study treatment | 25 percentage of participants |
| Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID | Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma | AEs considered as dose limiting toxicities | 25 percentage of participants |
| Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID | Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma | Serious adverse events | 0 percentage of participants |
| Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID | Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma | Serious adverse events related to study treatment | 0 percentage of participants |
| Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID | Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma | Adverse events leading to death | 0 percentage of participants |
| Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID | Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma | Serious adverse events | 44.4 percentage of participants |
| Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID | Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma | Any primary system organ class | 100 percentage of participants |
| Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID | Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma | AEs leading to withdrawal from any study treatment | 44.4 percentage of participants |
| Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID | Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma | Any AE | 100 percentage of participants |
| Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID | Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma | Adverse events leading to death | 0 percentage of participants |
| Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID | Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma | AEs related to both PLX3397 and vemurafenib | 55.6 percentage of participants |
| Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID | Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma | AEs considered as dose limiting toxicities | 33.3 percentage of participants |
| Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID | Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma | AEs related to PLX3397 | 77.8 percentage of participants |
| Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID | Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma | Serious adverse events related to study treatment | 22.2 percentage of participants |
| Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID | Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma | AEs related vemurafenib | 77.8 percentage of participants |