N/A
N=6
A Study of PLX3397 in Patients With Unresectable or Metastatic KIT-mutated Melanoma
Melanoma
Bottom Line
View on ClinicalTrials.gov: NCT02975700 ↗Enrolled (actual)
6
Serious AEs
33.3%
Results posted
Apr 2020
Primary outcome: Primary: Summary of Best Overall Response Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma — 0; 1; 2; 1 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- N/A
- Interventions
- PLX3397 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Daiichi Sankyo Co., Ltd.
- Primary completion
- Aug 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Summary of Best Overall Response Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma |
0; 1; 2; 1; 2 | — |
| PRIMARY Objective Response Rate (ORR) Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma |
1 | — |
| SECONDARY Duration of Response Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma |
NA | — |
| SECONDARY Progression-free Survival Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma |
10.32 | — |
| SECONDARY Overall Survival Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma |
NA | — |
| SECONDARY Disease Control Rate Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma |
3 | — |
| SECONDARY 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 |
4660; 9570 | — |
| SECONDARY 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 |
14500; 43800 | — |
| SECONDARY 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 |
2.72; 2.77; 5.99; 6.03 | — |
| SECONDARY 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 |
3.39 | — |
| SECONDARY 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 |
2.34 | — |
| SECONDARY 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 |
6; 6; 5; 5; 4; 4 | — |
| SECONDARY 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 |
4; 4; 2; 2; 1; 1 | — |
| SECONDARY 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 |
6; 6; 5; 5; 4; 4 | — |
| SECONDARY 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 |
4; 4; 2; 2; 1; 1 | — |
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.
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT02975700). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.