This is a Phase 1, open-label, dose-escalation and expansion study, evaluating the safety, tolerability, pharmacokinetics (PK), preliminary antitumor activity, and effect on biomarkers of XL092 administered alone, in combination with atezolizumab, and in combination with avelumab to subjects with advanced solid tumors.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
325
oral doses of XL092
Supplied as 1200 mg/20 mL vials; administered as a 1200 mg IV infusion once every 3 weeks (q3w)
Supplied as 200 mg/10 mL vials; administered as an 800 mg IV infusion once every 2 weeks (q2w)
Exelixis Clinical Site #6
Duarte, California, United States
Exelixis Clinical Site #49
La Jolla, California, United States
Exelixis Clinical Site #7
Los Angeles, California, United States
Exelixis Clinical Site #84
Los Angeles, California, United States
Exelixis Clinical Site #66
San Francisco, California, United States
Dose-Escalation Stage: MTD/recommended dose for XL092
To determine the maximum tolerated dose (MTD) and/or recommended dose (RD) for further evaluation of XL092 when administered alone and in combination with immune checkpoint inhibitors (ICIs) to subjects with advanced solid tumors
Time frame: Up to 24 months
Cohort-Expansion Stage: Objective Response Rate (ORR)
To evaluate preliminary efficacy of XL092 when administered alone and in combination with ICIs by estimating ORR as assessed by the Investigator per RECIST 1.1
Time frame: Up to 24 months
Cohort-Expansion Stage (except Cohort H): Progression-Free Survival (PFS)
To evaluate preliminary efficacy of single-agent XL092 and XL092 in combination with ICIs for specific cohorts by estimating the percentage of subjects with PFS at 6 months (PFS rate) per RECIST 1.1 as assessed by the Investigator (except for the CRC expansion cohort H)
Time frame: Up to 24 months
Cohort-Expansion Stage (Cohort H only): Overall Survival (OS)
To evaluate preliminary efficacy of single-agent XL092 and XL092 in combination with atezolizumab for subjects with RAS wild-type CRC (Cohort H Treatment Arms H-A and H-B) by estimating overall survival (OS)
Time frame: Up to 24 months
Incidence and Severity of Nonserious Adverse Events (AEs) and Serious Adverse Events (SAEs)
To evaluate the safety of XL092 when administered alone and in combination with ICIs through the evaluation of incidence and severity of nonserious AEs and SAEs, including immune-related adverse events (irAEs), and adverse events of special interest (AESIs)
Time frame: Up to 36 months
Dose-Escalation Stage: Time to Maximum Plasma Concentration (Tmax)
To evaluate the Tmax of XL092 alone and in combination with ICI
Time frame: Up to 24 months
Dose-Escalation Stage: Maximum Plasma Concentration (Cmax)
To evaluate the Cmax of XL092 alone and in combination with ICI
Time frame: Up to 24 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 XL092 alone and in combination with ICI
Time frame: Up to 24 months
Dose-Escalation Stage: Terminal Half-Life
To evaluate the terminal half-life of XL092 alone and in combination with ICI
Time frame: Up to 24 months
Dose-Escalation Stage: Apparent Clearance (CL/F)
To evaluate the CL/F of XL092 alone and in combination with ICI
Time frame: Up to 24 months
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Exelixis Clinical Site #71
Stanford, California, United States
Exelixis Clinical Site #15
Lake Mary, Florida, United States
Exelixis Clinical Site #24
Miami, Florida, United States
Exelixis Clinical Site #11
Atlanta, Georgia, United States
Exelixis Clinical Site #80
Atlanta, Georgia, United States
...and 76 more locations