A Dose-Escalation and Expansion Study of the Safety and Pharmacokinetics of XL092 as Single-Agent and Combination Therapy in Subjects with Inoperable Locally Advanced or Metastatic Solid Tumors
Objective
Primary Objectives: Dose-Escalation Stage: MTD/recommended dose for XL092 [ Time Frame: Up to 24 months ] 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 Cohort-Expansion Stage: Objective Response Rate (ORR) [ Time Frame: Up to 24 months ] 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 Cohort-Expansion Stage (except Cohort H): Progression-Free Survival (PFS) [ Time Frame: Up to 24 months ] 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 Cohort-Expansion Stage (Cohort H only): Overall Survival (OS) [ Time Frame: Up to 24 months ] 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).
Secondary Objectives: Incidence and Severity of Nonserious Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 36 months ] 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) Dose-Escalation Stage: Time to Maximum Plasma Concentration (Tmax) [ Time Frame: Up to 24 months ] To evaluate the Tmax of XL092 alone and in combination with ICI Dose-Escalation Stage: Maximum Plasma Concentration (Cmax) [ Time Frame: Up to 24 months ] To evaluate the Cmax of XL092 alone and in combination with ICI Dose-Escalation Stage: Area Under the Plasma Concentration-Time Curve Over the Last 24-hour Dosing Interval (AUC 0-24) [ Time Frame: Up to 24 months ] To evaluate the AUC 0-24 of XL092 alone and in combination with ICI Dose-Escalation Stage: Terminal Half-Life [ Time Frame: Up to 24 months ] To evaluate the terminal half-life of XL092 alone and in combination with ICI Dose-Escalation Stage: Apparent Clearance (CL/F) [ Time Frame: Up to 24 months ] To evaluate the CL/F of XL092 alone and in combination with ICI
