This is a Phase 1, non-randomized, open-label, dose-escalation and expansion study, evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical antitumor activity of XL114 administered alone orally to subjects with Non-Hodgkin's Lymphoma (NHL). The objectives of the study also include determining the recommended dose (RD) and/or maximum tolerated dose (MTD) of XL114.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
2
Tablets of XL114
Exelixis Clinical Site #3
Tucson, Arizona, United States
Exelixis Clinical Site #1
Indianapolis, Indiana, United States
Exelixis Clinical #4
Pittsburgh, Pennsylvania, United States
Exelixis Clinical Site #2
Spokane, Washington, United States
Dose-Escalation Stage: Recommended Dose (RD) and/or Maximum Tolerated Dose (MTD) for XL114
To determine the RD and/or MTD of XL114 administered orally in subjects with NHL
Time frame: 4-6 months
Cohort-Expansion Stage: Objective Response Rate (ORR)
To evaluate preliminary efficacy of XL114 by estimating the ORR based on lymphoma-specific response criteria as assessed by the Investigator
Time frame: 4-6 months
Safety of XL114, as evaluated by Adverse Events (AEs)
To evaluate the safety of XL114 through the evaluation of incidence and severity of treatment emergent nonserious adverse events (AEs) and serious adverse events (SAEs)at each dose level and their relationship to study drug treatment.
Time frame: 4-6 months
Tolerability of XL114, as evaluated by Dose Intensity, Dose Modifications, and Study Discontinuation due to AEs
To evaluate the tolerability of XL114 through the evaluation of dose intensity, dose modifications and study treatment discontinuation due to AEs related to XL114.
Time frame: 4-6 months
Dose-Escalation Stage: Time to Maximum Plasma Concentration (Tmax)
To evaluate the Tmax of XL114.
Time frame: 4-6 months
Dose-Escalation Stage: Maximum Plasma Concentration (Cmax)
To evaluate the Cmax of XL114.
Time frame: 4-6 months
Dose-Escalation Stage: Area Under the Plasma Concentration-Time Curve Over the Last 24-hour Dosing Interval (AUC 0-24)
To evaluate the AUC 0-24 of XL114.
Time frame: 4-6 months
Dose-Escalation Stage: Terminal Half-Life
To evaluate the terminal half-life of XL114.
Time frame: 4-6 months
Dose-Escalation Stage: Apparent Clearance (CL/F)
To evaluate the CL/F of XL114.
Time frame: 4-6 months
Cohort-Expansion Stage: Antitumor Activity of XL114 (Objective Response Rate [ORR])
To evaluate the antitumor activity of XL114 as measured by ORR based on lymphoma-specific response criteria as assessed by a Blinded Independent Radiology Committee (BIRC) for selected cohorts.
Time frame: 4-6 months
Cohort-Expansion Stage: Antitumor Activity of XL114 (Duration of Response [DOR])
To evaluate the antitumor activity of XL114 as measured by DOR based on lymphoma-specific response criteria as assessed by the Investigator or by a Blinded Independent Radiology Committee (BIRC) for selected cohorts.
Time frame: 4-6 months
Cohort-Expansion Stage: Antitumor Activity of XL114 (Progression Free Survival [PFS])
To evaluate the antitumor activity of XL114 as measured by PFS based on lymphoma-specific response criteria as assessed by the Investigator or by a Blinded Independent Radiology Committee (BIRC) for selected cohorts.
Time frame: 4-6 months
Cohort-Expansion Stage: Overall Survival (OS) of XL114
To evaluate duration of overall survival (OS)
Time frame: 4-6 months
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