Capsules administered once or twice daily, continuous dosing

PLX3397

Medical Director

PLX3397 is a selective inhibitor of Fms, Kit, and oncogenic Flt3 activity. The primary objective of this study is to evaluate the safety and pharmacokinetics of orally administered PLX3397 in patients with advanced, incurable, solid tumors in which these target kinases are linked to disease pathophysiology. The secondary objective is to measure the pharmacodynamic activity of PLX3397 via blood, plasma and urine biomarkers of Fms activity.

Safety Study of PLX108-01 in Patients With Solid Tumors

A Phase 1 Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of PLX3397 in Patients With Advanced, Incurable, Solid Tumors in Which the Target Kinases Are Linked to Disease Pathophysiology

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Best overall tumor response (complete response \[CR\], partial response \[PR\], stable disease \[SD\], progressive disease \[PD\]) is reported, including participants who were not evaluable (NE).

RECIST v1.1 for target lesions are assessed by magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography and are summarized as: CR, Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm; PR, At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). In addition, the sum must also demonstrate an absolute increase of at least 5 mm; SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Duration of Response (DOR) is defined as the number of days from the date of initial response (CR or PR confirmed at least 28 days later) to the date of first documented disease progression/relapse or death, whichever occurs first. If no disease progression or death is documented prior to study termination, analysis cutoff, or the start of confounding anticancer therapy, DOR is censored as of the date of their last imaging exam of target or non-target lesions prior to post-surgery and/or off-treatment scans.

Progression-Free Survival (PFS) is defined as the number of days from the first day of treatment to the first documented disease progression or date of death, whichever occurs first. If no disease progression or death is documented prior to study termination, analysis cutoff, or the start of confounding anticancer therapy, PFS is censored at the date of last evaluable tumor assessment.

Cycle 1 Day 15 pharmacokinetic (PK) timepoints taken are: For once daily (QD) dosing, obtained predose (morning) and 0.5, 1, 2, 4, and 8 hours postdose. For twice a day (BID) dosing predose (morning) and 1, 2, 4, and 7 hours postdose. The second dose will then be administered, and PK obtained 1 hour post the second dose (8 hours post the first dose). For BID dosing, no run-in is planned.

Cycle 1 Day 15 PK timepoints taken are: For QD dosing, obtained predose (morning) and 0.5, 1, 2, 4, and 8 hours postdose. For BID dosing predose (morning) and 1, 2, 4, and 7 hours postdose. The second dose will then be administered, and PK obtained 1 hour post the second dose (8 hours post the first dose). For BID dosing, no run-in is planned.

Cycle 1 Day 15 PK timepoints taken are: For QD dosing, obtained predose (morning) and 0.5, 1, 2, 4, and 8 hours postdose. For BID dosing, predose (morning) and 1, 2, 4, and 7 hours postdose. The second dose will then be administered, and PK obtained 1 hour post the second dose (8 hours post the first dose). For BID dosing, no run-in is planned.

The NRS for PVNS Symptoms instrument is a 5-item self-administered questionnaire to assess the "worst" of each of the symptoms pain, swelling, stiffness, instability and limited motion in the last 24 hours. A 0 to 10 NRS is provided for each symptom. For pain, 0 indicates "no pain" and 10 indicates "pain as bad as you can imagine". For the other 4 symptoms, 0 indicates "no (symptom)" and 10 indicates "(symptom) worst imaginable", e.g., "swelling - worst imaginable." Higher scores indicated worse outcome.

Plexxikon

Daiichi Sankyo

Participants with advanced, incurable, solid tumors who received PLX3397 200 mg QD.

Dose Escalation Cohort 1: 200 mg QD

Participants with advanced, incurable, solid tumors who received PLX3397 300 mg QD.

Dose Escalation Cohort 2: 300 mg QD

Participants with advanced, incurable, solid tumors who received PLX3397 400 mg QD.

Dose Escalation Cohort 3: 400 mg QD

Participants with advanced, incurable, solid tumors who received PLX3397 600 mg QD.

Dose Escalation Cohort 4: 600 mg QD

Participants with advanced, incurable, solid tumors who received PLX3397 900 mg/day.

Dose Escalation Cohort 5: 900 mg/Day (500mg AM, 400mg PM)

Participants with advanced, incurable, solid tumors who received PLX3397 1200 mg/day.

Dose Escalation Cohort 6: 1200 mg/Day (600mg BID)

Participants with advanced, incurable, solid tumors who received PLX3397 1000 mg/day.

Dose Escalation Cohort 7: 1000 mg/Day (500mg BID)

Participants with advanced or recurrent mucoepidermoid carcinoma (MEC) who received PLX3397.

MEC Cohort 1000 mg/Day (600mg AM, 400mg PM)

Participants with advanced pigmented villonodular synovitis (PVNS) who received PLX3397.

PVNS Cohort 1000 mg/Day (600mg AM, 400mg PM)

Participants with advanced gastrointestinal stromal tumor (GIST) who received PLX3397.

GIST Cohort 1000 mg/Day (600mg AM, 400mg PM)

Participants with anaplastic thyroid carcinoma (ATC) who received PLX3397.

ATC Cohort 1000 mg/Day (600mg AM, 400mg PM)

Participants with advanced solid tumors with malignant effusion who received PLX3397.

Malignant Effusion Cohort 1000 mg/Day (600mg AM, 400mg PM)

Participants with other solid tumor types who received PLX3397.

Other Solid Tumor Type Cohort 1000 mg/Day (600mg AM, 400mg PM)

Dose Escalation Cohort 5: 900 mg/Day

Dose Escalation Cohort 6: 1200 mg/Day

Dose Escalation Cohort 7: 1000 mg/Day

Participants with advanced mucoepidermoid carcinoma (MEC) who received PLX3397.

Dose Extension: MEC Cohort

Dose Extension: PVNS Cohort

Participants with advanced gastrointestinal stromal tumor (GIS) who received PLX3397.

Dose Extension: GIST Cohort

Dose Extension: ATC Cohort

Dose Extension: Malignant Effusion Cohort

Dose Extension: Other Solid Tumor Type Cohort

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Asian

White

Black of African American

Native Hawaiian or Other Pacific Islander

Multiple races

Race/Ethnicity, Customized

United States

Region of Enrollment

Censored participants

All participants with advanced, incurable, solid tumors who received PL3397.

All Participants

Best overall tumor response was assessed in the Efficacy Evaluable Population.

Summary of Derived Best Tumor Response Per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - Dose Escalation (Efficacy Evaluable Population)

Overall response rate (CR or PR)

Summary of Derived Best Tumor Response Per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - Dose Extension (Efficacy Evaluable Population)

Duration of response was assessed among participants with response of CR or PR in the Efficacy Evaluable Population.

Duration of Response (Efficacy Evaluable Population) - Dose Extension

Progression-free survival was assessed in the Efficacy Evaluable Population.

Progression-free Survival (Efficacy Evaluable Population) - Dose Extension

PVNS Cohort

Best Overall Tumor Response (PVNS Cohort) Per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - Dose Extension

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.

Summary Statistics for Selected PLX3397 Pharmacokinetics Parameter Cmax, Study Day Cycle 1 Day 15, Stratified by Cohort - Dose Escalation

Summary Statistics for Selected PLX3397 Pharmacokinetics Parameter Tmax, Study Day Cycle 1 Day 15, Stratified by Cohort - Dose Escalation

Summary Statistics for Selected PLX3397 Pharmacokinetics Parameter Area Under the Curve (AUC0-24), Study Day Cycle 1 Day 15, Stratified by Cohort - Dose Escalation

Pain; Baseline

Pain; Cycle 1 Day 15

Pain; Cycle 2

Pain; Cycle 3

Pain; Cycle 12

Pain; Cycle 24

Pain; Cycle 36

Pain; Cycle 46

Swelling; Baseline

Swelling; Cycle 1 Day 15

Swelling; Cycle 2

Swelling; Cycle 3

Swelling; Cycle 12

Swelling; Cycle 24

Swelling; Cycle 36

Swelling; Cycle 46

Stiffness; Baseline

Stiffness; Cycle 1 Day 15

Stiffness; Cycle 2

Stiffness; Cycle 3

Stiffness; Cycle 12

Stiffness; Cycle 24

Stiffness; Cycle 36

Stiffness; Cycle 46

Instability; Baseline

Instability; Cycle 1 Day 15

Instability; Cycle 2

Instability; Cycle 3

Instability; Cycle 12

Instability; Cycle 24

Instability; Cycle 36

Instability; Cycle 46

Limited motion; Baseline

Limited motion; Cycle 1 Day 15

Limited motion; Cycle 2

Limited motion; Cycle 3

Limited motion; Cycle 12

Limited motion; Cycle 24

Limited motion; Cycle 36

Limited Motion; Cycle 46

Participants who were administered the NRS scale at baseline and monthly on treatment.

NRS for PVNS Symptoms Evaluable Population

NRS for PVNS symptoms were assessed in patients with available data in the Efficacy Evaluable Population.

Spots Global Cancer Trial Database for Safety Study of PLX108-01 in Patients With Solid Tumors

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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