A Phase 1b Open Label, Dose Escalation Study of PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma

Daiichi Sankyo

Status and phase: Terminated; Phase 1

Conditions: V600-mutated BRAF Unresectable Melanoma; Stage III or Stage IV Metastatic Melanoma That Has Not Been Previously Treated With a Selective BRAF Inhibitor; V600-mutated BRAF Metastatic Melanoma

Treatments: Drug: PLX3397; Drug: vemurafenib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01826448

PLX108-09

Details and patient eligibility

About

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.

Enrollment: 13 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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13 participants in 4 patient groups

Dose extension cohort

Experimental group

Description:

Patients will take PLX3397 and vemurafenib at the recommended phase 2 dose. This will be determined by the tolerability and safety of these drugs in the previous 3 cohorts.

Treatment:

Drug: PLX3397

Drug: vemurafenib

Cohort 3

Experimental group

Description:

Patients will take 1000mg/day of PLX3397 and 960mg BID of vemurafenib

Treatment:

Drug: PLX3397

Drug: vemurafenib

Cohort 2

Experimental group

Description:

Patients will take 800mg/day of PLX3397 and 960mg BID of vemurafenib

Treatment:

Drug: PLX3397

Drug: vemurafenib

Cohort 1

Experimental group

Description:

Patients will take 800mg/day of PLX3397 and 720mg BID of vemurafenib

Treatment:

Drug: PLX3397

Drug: vemurafenib