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

Daiichi Sankyo Co., Ltd.6 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Melanoma

Interventions

PLX3397DRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (5)

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Sun Yat-sen Hospital

Guangzhou, Guangdong, China

Samsung Medical Center

Seoul, Gangnam-Gu, South Korea

Severance Hospital, Yonsei University Health System

Seoul, Seodaemun-gu, South Korea

Outcomes

Primary Outcomes

Summary of Best Overall Response Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma

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

Objective Response Rate (ORR) Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma

Objective response rate was defined as complete response (CR) or partial response (PR).

Time frame: within 18 months postdose

Secondary Outcomes

Duration of Response Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma

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

Progression-free Survival Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma

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.

Data from ClinicalTrials.gov

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