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

• Sponsor: Daiichi Sankyo Co., Ltd. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02975700
• Collaborator: Daiichi Sankyo, Inc. (Industry)
• Enrollment: 6
• Locations: 5
• Arm: 1
• Duration (Months): 73.9
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Melanoma	Drug: PLX3397	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Open Label, Multicenter Study of PLX3397 in Patients With Unresectable or Metastatic KIT-mutated Melanoma
• Study Start Date: Jan 1, 2017
• Actual Primary Completion Date: Aug 31, 2018
• Anticipated Study Completion Date: Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PLX3397 Part 1: Open label, multicenter study includes a dose evaluation portion in which the safety profile of PLX3397 as a single oral agent will be evaluated Part 2: An expansion cohort in which the efficacy and safety of PLX3397 administered at the recommended Phase 2 dose will be evaluated in patients with unresectable stage III or stage IV KIT-mutated melanoma.	Drug: PLX3397; Other Names: Pexidartinib

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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).

5. 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]

6. 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]

7. 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]

8. 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]

9. 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]

10. 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]

11. 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.

12. 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]

13. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beijing Cancer Hospital	Beijing	Beijing	China	100142
2	Sun Yat-sen Hospital	Guangzhou	Guangdong	China
3	Samsung Medical Center	Seoul	Gangnam-Gu	Korea, Republic of	06351
4	Severance Hospital, Yonsei University Health System	Seoul	Seodaemun-gu	Korea, Republic of	03722
5	Seoul National University Hospital	Seoul		Korea, Republic of

Sponsors and Collaborators

• Daiichi Sankyo Co., Ltd.
• Daiichi Sankyo, Inc.

Investigators

• Study Director: Global Clinical Leader, Daiichi Sankyo, Inc.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 25, 2020

More Information

Publications

None provided.

• Responsible Party: Daiichi Sankyo Co., Ltd.
• ClinicalTrials.gov Identifier: NCT02975700
• Other Study ID Numbers: PLX108-13
• First Posted: Nov 29, 2016
• Last Update Posted: Apr 22, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Daiichi Sankyo Co., Ltd.: PLX3397; Kit-mutant Melanoma; Unresectable or Metastatic KIT-mutated Melanoma; Developmental Phase I/II
• Additional relevant MeSH terms: Melanoma

Study Results

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.

Arm/Group Title	PLX3397
Arm/Group Description	Participants who received PLX3397 1000 mg/day (400 mg in the morning and 600 mg in the evening).
Period Title: Overall Study
STARTED	6
COMPLETED	0
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	PLX3397
Arm/Group Description	Participants who received PLX3397 1000 mg/day (400 mg in the morning and 600 mg in the evening).
Overall Participants	6
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 66.7%
>=65 years	2 33.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.5 (14.5)
Sex: Female, Male (Count of Participants)
Female	4 66.7%
Male	2 33.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	6 100%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
China	6 100%

Outcome Measures

1. Primary Outcome

Title	Summary of Best Overall Response Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Description	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.
Time Frame	within 18 months postdose

Outcome Measure Data

Analysis Population Description

Best overall response was assessed in the Modified Intent-to-Treat Analysis Set.

Arm/Group Title	PLX3397
Arm/Group Description	Participants who received PLX3397 1000 mg/day (400 mg in the morning and 600 mg in the evening).
Measure Participants	6
Complete response (CR)	0 0%
Partial response (PR)	1 16.7%
Stable disease (SD)	2 33.3%
Progressive disease (PD)	1 16.7%
Not evaluable (NE)	2 33.3%

2. Primary Outcome

Title	Objective Response Rate (ORR) Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Description	Objective response rate was defined as complete response (CR) or partial response (PR).
Time Frame	within 18 months postdose

Outcome Measure Data

Analysis Population Description

Objective response rate among participants who achieved complete response or partial response was assessed in the Modified Intent-to-Treat Analysis Set.

Arm/Group Title	PLX3397
Arm/Group Description	Participants who received PLX3397 1000 mg/day (400 mg in the morning and 600 mg in the evening).
Measure Participants	6
Count of Participants [Participants]	1 16.7%

3. Secondary Outcome

Title	Duration of Response Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Description	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.
Time Frame	within 18 months postdose

Outcome Measure Data

Analysis Population Description

Duration of response was assessed in the Modified Intent-to-Treat Analysis Set.

Arm/Group Title	PLX3397
Arm/Group Description	Participants who received PLX3397 1000 mg/day (400 mg in the morning and 600 mg in the evening).
Measure Participants	1
Median (Full Range) [months]	NA

4. Secondary Outcome

Title	Progression-free Survival Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Description	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.
Time Frame	within 18 months postdose

Outcome Measure Data

Analysis Population Description

Progression-free survival was assessed in the Modified Intent-to-Treat Analysis Set.

Arm/Group Title	PLX3397
Arm/Group Description	Participants who received PLX3397 1000 mg/day (400 mg in the morning and 600 mg in the evening).
Measure Participants	6
Median (95% Confidence Interval) [months]	10.32

5. Secondary Outcome

Title	Overall Survival Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Description	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.
Time Frame	within 18 months postdose

Outcome Measure Data

Analysis Population Description

Overall survival was assessed in the Modified Intent-to-Treat Analysis Set.

Arm/Group Title	PLX3397
Arm/Group Description	Participants who received PLX3397 1000 mg/day (400 mg in the morning and 600 mg in the evening).
Measure Participants	6
Median (95% Confidence Interval) [months]	NA

6. Secondary Outcome

Title	Disease Control Rate Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Description	Disease control rate (DCR) was defined as the percentage of participants who had achieved complete response (CR), partial response (PR), or stable disease (SD).
Time Frame	within 18 months postdose

Outcome Measure Data

Analysis Population Description

Disease control rate among participants who achieved CR, PR, or SD was assessed in the Modified Intent-to-Treat Analysis Set.

Arm/Group Title	PLX3397
Arm/Group Description	Participants who received PLX3397 1000 mg/day (400 mg in the morning and 600 mg in the evening).
Measure Participants	6
Count of Participants [Participants]	3 50%

7. Secondary Outcome

Title	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
Time Frame	Cycle 1, Day 1 and Day 15 at predose, 0.5 h, 1h, 2h, 4h, and 6h postdose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.

Arm/Group Title	PLX3397
Arm/Group Description	Participants who received PLX3397 1000 mg/day (400 mg in the morning and 600 mg in the evening).
Measure Participants	6
Day 1	4660 (1830)
Day 15	9570 (2940)

8. Secondary Outcome

Title	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
Time Frame	Cycle 1, Day 1 and Day 15 at predose, 0.5 h, 1h, 2h, 4h, and 6h postdose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.

Arm/Group Title	PLX3397
Arm/Group Description	Participants who received PLX3397 1000 mg/day (400 mg in the morning and 600 mg in the evening).
Measure Participants	6
Day 1	14500 (4660)
Day 15	43800 (7010)

9. Secondary Outcome

Title	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
Time Frame	Cycle 1, Day 1 and Day 15 at predose, 0.5 h, 1h, 2h, 4h, and 6h postdose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.

Arm/Group Title	PLX3397
Arm/Group Description	Participants who received PLX3397 1000 mg/day (400 mg in the morning and 600 mg in the evening).
Measure Participants	6
Time to maximum concentration; Day 1	2.72 (1.62)
Time to maximum concentration; Day 15	2.77 (2.31)
Last measurable time; Day 1	5.99 (0.05)
Last measurable time; Day 15	6.03 (0.06)

10. Secondary Outcome

Title	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
Time Frame	Cycle 1, Day 1 and Day 15 at predose, 0.5 h, 1h, 2h, 4h, and 6h postdose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.

Arm/Group Title	PLX3397
Arm/Group Description	Participants who received PLX3397 1000 mg/day (400 mg in the morning and 600 mg in the evening).
Measure Participants	5
Mean (Standard Deviation) [Ratio]	3.39 (0.85)

11. Secondary Outcome

Title	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
Time Frame	Cycle 1, Day 1 and Day 15 at predose, 0.5 h, 1h, 2h, 4h, and 6h postdose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.

Arm/Group Title	PLX3397
Arm/Group Description	Participants who received PLX3397 1000 mg/day (400 mg in the morning and 600 mg in the evening).
Measure Participants	5
Mean (Standard Deviation) [Ratio]	2.34 (0.69)

12. Secondary Outcome

Title	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
Time Frame	within 28 days after administration of the last dose of study drug, up to 18 months postdose

Outcome Measure Data

Analysis Population Description

Safety events were assessed in the Safety Analysis Set.

Arm/Group Title	PLX3397
Arm/Group Description	Participants who received PLX3397 1000 mg/day (400 mg in the morning and 600 mg in the evening).
Measure Participants	6
Aspartate aminotransferase increased	6 100%
White blood cell count decreased	6 100%
Anaemia	5 83.3%
Face oedema	5 83.3%
Alanine aminotransferase increased	4 66.7%
Blood bilirubin increased	4 66.7%
Gamma-glutamyltransferase increased	4 66.7%
Hair colour changes	4 66.7%
Neutrophil count decreased	4 66.7%
Bilirubin conjugated increased	3 50%
Blood alkaline phosphatase increased	3 50%
Blood lactate dehydrogenase increased	3 50%
Interstitial lung disease	3 50%
Pyrexia	3 50%
Total bile acids increased	3 50%

13. Secondary Outcome

Title	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
Description	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.
Time Frame	within 28 days after administration of the last dose of study drug, up to 18 months postdose

Outcome Measure Data

Analysis Population Description

Safety events were assessed in the Safety Analysis Set.

Arm/Group Title	PLX3397
Arm/Group Description	Participants who received PLX3397 1000 mg/day (400 mg in the morning and 600 mg in the evening).
Measure Participants	6
Any TEAEs CTCAE Grade ≥ 3	4 66.7%
Gamma-glutamyltransferase increased	4 66.7%
Alanine aminotransferase increased	2 33.3%
Total bile acids increased	2 33.3%
Anaemia	1 16.7%
Aspartate aminotransferase increased	1 16.7%
Bilirubin conjugated increased	1 16.7%
Blood alkaline phosphatase increased	1 16.7%
Blood bilirubin increased	1 16.7%
Drug-induced liver injury	1 16.7%
Herpes zoster	1 16.7%
Hypertension	1 16.7%
Neutrophil count decreased	1 16.7%
White blood cell count decreased	1 16.7%

14. Secondary Outcome

Title	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
Time Frame	within 28 days after administration of the last dose of study drug, up to 18 months postdose

Outcome Measure Data

Analysis Population Description

Safety events were assessed in the Safety Analysis Set.

Arm/Group Title	PLX3397
Arm/Group Description	Participants who received PLX3397 1000 mg/day (400 mg in the morning and 600 mg in the evening).
Measure Participants	6
Aspartate aminotransferase increased	6 100%
White blood cell count decreased	6 100%
Anaemia	5 83.3%
Face oedema	5 83.3%
Alanine aminotransferase increased	4 66.7%
Blood bilirubin increased	4 66.7%
Gamma-glutamyltransferase increased	4 66.7%
Hair colour changes	4 66.7%
Neutrophil count decreased	4 66.7%
Bilirubin conjugated increased	3 50%
Blood alkaline phosphatase increased	3 50%
Blood lactate dehydrogenase increased	3 50%
Interstitial lung disease	3 50%
Total bile acids increased	3 50%

15. Secondary Outcome

Title	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
Description	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.
Time Frame	within 28 days after administration of the last dose of study drug, up to 18 months postdose

Outcome Measure Data

Analysis Population Description

Safety events were assessed in the Safety Analysis Set.

Arm/Group Title	PLX3397
Arm/Group Description	Participants who received PLX3397 1000 mg/day (400 mg in the morning and 600 mg in the evening).
Measure Participants	6
Any Drug-related TEAEs CTCAE Grade ≥ 3	4 66.7%
Gamma-glutamyltransferase increased	4 66.7%
Alanine aminotransferase increased	2 33.3%
Total bile acids increased	2 33.3%
Aspartate aminotransferase increased	1 16.7%
Bilirubin conjugated increased	1 16.7%
Blood alkaline phosphatase increased	1 16.7%
Blood bilirubin increased	1 16.7%
Drug-induced liver injury	1 16.7%
Neutrophil count decreased	1 16.7%
White blood cell count decreased	1 16.7%

Adverse Events

Time Frame	Adverse events were collected from after initiation of study drug up to 28 days after administration of last dose of study drug, up to 18 months postdose.
Arm/Group Title	PLX3397
Arm/Group Description	Participants who received PLX3397 1000 mg/day (400 mg in the morning and 600 mg in the evening).
All Cause Mortality
	PLX3397
	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)
Serious Adverse Events
	PLX3397
	Affected / at Risk (%)	# Events
Total	2/6 (33.3%)
Hepatobiliary disorders
Drug-induced liver injury	2/6 (33.3%)
Other (Not Including Serious) Adverse Events
	PLX3397
	Affected / at Risk (%)	# Events
Total	6/6 (100%)
Blood and lymphatic system disorders
Anaemia	5/6 (83.3%)
Eye disorders
Eyelid oedema	2/6 (33.3%)
Gastrointestinal disorders
Diarrhoea	2/6 (33.3%)
Abdominal pain	1/6 (16.7%)
Constipation	1/6 (16.7%)
Mouth ulceration	1/6 (16.7%)
General disorders
Face oedema	5/6 (83.3%)
Pyrexia	3/6 (50%)
Fatigue	1/6 (16.7%)
Hepatobiliary disorders
Drug-induced liver injury	2/6 (33.3%)
Infections and infestations
Conjunctivitis	1/6 (16.7%)
Herpes zoster	1/6 (16.7%)
Upper respiratory tract infection	1/6 (16.7%)
Investigations
Aspartate aminotransferase increased	6/6 (100%)
White blood cell count decreased	6/6 (100%)
Alanine aminotransferase increased	4/6 (66.7%)
Blood bilirubin increased	4/6 (66.7%)
Gamma-glutamyltransferase increased	4/6 (66.7%)
Neutrophil count decreased	4/6 (66.7%)
Bilirubin conjugated increased	3/6 (50%)
Blood alkaline phosphatase increased	3/6 (50%)
Blood lactate dehydrogenase increased	3/6 (50%)
Red blood cell count decreased	2/6 (33.3%)
Blood creatinine phosphokinase increased	1/6 (16.7%)
Blood potassium decreased	1/6 (16.7%)
Blood triglycerides increased	1/6 (16.7%)
Blood urea increased	1/6 (16.7%)
Blood uric acid increases	1/6 (16.7%)
Creatinine renal clearance decreased	1/6 (16.7%)
Electrocardiogram QT prolonged	1/6 (16.7%)
Glucose urine present	1/6 (16.7%)
Urine ketone body present	1/6 (16.7%)
Metabolism and nutrition disorders
Hypokalemia	2/6 (33.3%)
Decreased appetite	1/6 (16.7%)
Nervous system disorders
Headache	1/6 (16.7%)
Renal and urinary disorders
Proteinuria	1/6 (16.7%)
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease	3/6 (50%)
Rhinitis allergic	1/6 (16.7%)
Skin and subcutaneous tissue disorders
Hair colour changes	4/6 (66.7%)
Rash	1/6 (16.7%)
Vascular disorders
Hypertension	1/6 (16.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.