A Study of PLX3397 in Patients With Unresectable or Metastatic KIT-mutated Melanoma

A Phase I/II Open Label, Multicenter Study of PLX3397 in Patients With Unresectable or Metastatic KIT-mutated Melanoma

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02975700

Enrollment

Registered

2016-11-29

Start date

2017-01-31

Completion date

2024-10-11

Last updated

2026-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Melanoma

Keywords

PLX3397, Kit-mutant Melanoma, Unresectable or Metastatic KIT-mutated Melanoma, Developmental Phase I/II

Brief summary

The purpose of this Phase I/II study is to evaluate safety, pharmacokinetics, and preliminary efficacy of the investigational drug PLX3397 in subjects with unresectable or metastatic KIT-mutated melanoma.

Interventions

DRUGPLX3397

1000 mg/day (400 mg in the morning and 600 mg in the evening)

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Age ≥ 18 years * Unresectable stage III or stage IV melanoma which is histologically confirmed at the treating institution with KIT mutation(s) not known to be resistant to PLX3397 * Presence of measurable lesions by Response Evaluation Criteria in Solid Tumors * Eastern Cooperative Oncology Group (ECOG) performance Status (PS) 0-2 * Life expectancy ≥ 3 months * Adequate organ and bone marrow function * Women of child-bearing potential must have a negative serum pregnancy test at Screening and must agree to use an effective form of contraception from the time of the negative pregnancy test up to 3 months after the last dose of study drug. Women of non-child-bearing potential must have been postmenopausal for ≥ 1 year or surgically sterile. * Fertile men must agree to use an effective method of birth control during the study and for up to 3 months after the last dose of study drug. * Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements

Exclusion criteria

* Prior treatment with a KIT inhibitor for melanoma * Presence of NRAS or BRAF mutation * Exposure to any investigational drug within 28 days or unresolved adverse effects from previous therapy * Symptomatic brain metastases. * Active secondary malignancy unless the malignancy is not expected to interfere with the evaluation of safety and is approved by the Sponsor * Concomitant treatment with other anti-neoplastic agents (hormonal therapy acceptable) * Uncontrolled intercurrent or infectious illness * Major surgical procedure or significant traumatic injury within 14 days of initiating study drug or anticipation of the need for major surgery during the study * Previous radiotherapy to 25% or more of the bone marrow and/or radiation therapy within 28 days prior to study entry * Inability to swallow capsules, or refractory nausea and vomiting, malabsorption, an external biliary shunt, or significant bowel resection that would preclude adequate absorption * Congestive heart failure (CHF) New York (NY) Heart Association class III or IV; unstable coronary artery disease \[myocardial infarction (MI) more than 6 months prior to study entry is permitted\] or serious cardiac arrhythmia * Baseline QT interval corrected using Fridericia equation (QTcF) ≥ 450 msec (for males) or ≥ 470 msec (for females) at Screening * Active or chronic infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) * Known chronic liver disease * Women who are breast-feeding or pregnant

Design outcomes

Primary

Measure	Time frame	Description
Summary of Best Overall Response Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma	within 18 months postdose	For the assessment of best overall response, participants were classified by RECIST v1.1: complete response (CR), disappearance of all target lesions and normalization of tumor marker level; partial response (PR), at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; stable disease (SD); neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study; progressive disease (PD), at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm; or not evaluable (NE) for analysis.
Objective Response Rate (ORR) Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma	within 18 months postdose	Objective response rate was defined as complete response (CR) or partial response (PR).

Secondary

Measure	Time frame	Description
Overall Survival Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma	within 18 months postdose	Overall survival (OS) was defined as the time from study enrollment to death from any cause, censoring at the date of last contact or the end of the study.
Disease Control Rate Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma	within 18 months postdose	Disease control rate (DCR) was defined as the percentage of participants who had achieved complete response (CR), partial response (PR), or stable disease (SD).
Summary of Pharmacokinetic Parameter of Maximum Concentration (Cmax) of PL3397 at Days 1 and 15 Following Twice Daily Administration of PL3397 at 1000 mg/Day in Participants With Unresectable or Advanced KIT-mutated Melanoma	Cycle 1, Day 1 and Day 15 at predose, 0.5 h, 1h, 2h, 4h, and 6h postdose	—
Summary of Pharmacokinetic Parameter of Area Under the Curve From Zero to 6 Hours (AUC0-6) of PL3397 at Days 1 and 15 Following Twice Daily Administration of PL3397 at 1000 mg/Day in Participants With Unresectable or Advanced KIT-mutated Melanoma	Cycle 1, Day 1 and Day 15 at predose, 0.5 h, 1h, 2h, 4h, and 6h postdose	—
Summary of Pharmacokinetic Parameter of Time to Maximum Concentration and Last Measurable Time of PL3397 at Days 1 and 15 Following Twice Daily Administration of PL3397 at 1000 mg/Day in Participants With Unresectable or Advanced KIT-mutated Melanoma	Cycle 1, Day 1 and Day 15 at predose, 0.5 h, 1h, 2h, 4h, and 6h postdose	—
Duration of Response Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma	within 18 months postdose	Duration of Response (DoR) was defined as the time from the first documentation of objective tumor response (complete response \[CR\] or partial response \[PR\]) to the first documentation of disease progression or to death due to any cause, whichever occurred first. DoR was to only be calculated for the subgroup of participants with an objective tumor response.
Summary of Pharmacokinetic Parameter of Accumulation Ratio of Day 15 to Day 1 for Cmax (Rcmax) of PL3397 at Day 15 Following Twice Daily Administration of PL3397 at 1000 mg/Day in Participants With Unresectable or Advanced KIT-mutated Melanoma	Cycle 1, Day 1 and Day 15 at predose, 0.5 h, 1h, 2h, 4h, and 6h postdose	—
Summary of Most Common (≥50% of Participants) Treatment-emergent Adverse Events Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma	within 28 days after administration of the last dose of study drug, up to 18 months postdose	—
Summary of Treatment-emergent Adverse Events Grade ≥ 3 Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma	within 28 days after administration of the last dose of study drug, up to 18 months postdose	Grade ≥ 3 was used to indicate moderate-to-severe treatment-emergent adverse events in which moderate was defined as discomfort enough to cause interference with normal daily activities and severe defined as the inability to perform normal daily activities.
Summary of Most Common (≥50%) Drug-related Treatment-emergent Adverse Events Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma	within 28 days after administration of the last dose of study drug, up to 18 months postdose	—
Summary of Drug-related Treatment-emergent Adverse Events Grade ≥ 3 Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma	within 28 days after administration of the last dose of study drug, up to 18 months postdose	Grade ≥ 3 was used to indicate moderate-to-severe treatment-emergent adverse events in which moderate was defined as discomfort enough to cause interference with normal daily activities and severe defined as the inability to perform normal daily activities.
Summary of Pharmacokinetic Parameter of Accumulation Ratio of Day 15 to Day 1 for AUC0-6h (Robs) of PL3397 at Day 15 Following Twice Daily Administration of PL3397 at 1000 mg/Day in Participants With Unresectable or Advanced KIT-mutated Melanoma	Cycle 1, Day 1 and Day 15 at predose, 0.5 h, 1h, 2h, 4h, and 6h postdose	—
Progression-free Survival Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma	within 18 months postdose	Progression-free survival (PFS) was to be calculated for each participant as the number of days from study enrollment to the date of the first documented disease progression or date of death from any cause, whichever occurred first.

Countries

China, South Korea

Participant flow

Recruitment details

A total of 8 participants entered the pilot portion of the study; no participants entered the phase 2 portion. Of the 8 participants, 2 failed screening criteria and did not receive treatment.

Participants by arm

Arm	Count
PLX3397 Participants who received PLX3397 1000 mg/day (400 mg in the morning and 600 mg in the evening).	6
Total	6

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1
Overall Study	Failed screening criteria	2
Overall Study	Progressive disease	3

Baseline characteristics

Characteristic	PLX3397
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	2 Participants
Age, Categorical Between 18 and 65 years	4 Participants
Age, Continuous	56.5 years STANDARD_DEVIATION 14.5
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	6 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	0 Participants
Region of Enrollment China	6 participants
Sex: Female, Male Female	4 Participants
Sex: Female, Male Male	2 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	1 / 6
other Total, other adverse events	6 / 6
serious Total, serious adverse events	2 / 6