An Open-Label, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of XL309 (ISM3091) as Single-Agent and Combination Therapy in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- XL309
- Conditions
- Advanced Solid Tumor
- Sponsor
- Exelixis
- Enrollment
- 429
- Locations
- 16
- Primary Endpoint
- Dose Escalation Stage: Incidence of TEAEs and SAEs; AEs Leading to Dose Modification, Discontinuation, or Death; and Laboratory Abnormalities
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
Brief Summary
This is a first-in-human (FIH), multicenter, open-label Phase I study to investigate the safety, tolerability, preliminary antitumor activity, as well as pharmacokinetics (PK) and pharmacodynamics of XL309 (previously ISM3091) administered alone or in combination with olaparib in participants with advanced solid tumors.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Capable of understanding and complying with protocol requirements.
- •Male or female aged 18 years or older.
- •Eastern Cooperative Oncology Group performance status 0 or
- •Adequate bone marrow and organ function.
- •Participant-disease Characteristics
- •Dose-Escalation Stage Single Agent and Combination:
- •a) Participants whose tumor progressed on, or who were intolerant to standard therapy, have a disease for which no therapy exists or are not a candidate for these therapies, and have one of the following cancers:
- •i. Histologically confirmed locally advanced/metastatic human epidermal growth factor receptor-2 (HER2)-negative breast cancer, with deleterious or suspected deleterious breast cancer gene (BRCA)1/2 alteration.
- •ii. Histologically confirmed locally advanced/metastatic high-grade serous ovarian cancer (HGSOC), including primary peritoneal cancer (PPC) and fallopian tube cancer (FTC).
- •iii. Histologically confirmed locally advanced/metastatic CRPC, with deleterious or suspected deleterious BRCA1/2 alteration.
Exclusion Criteria
- Not provided
Arms & Interventions
Dose Escalation Single Agent Evaluation
Participants will receive XL309 in sequential cohorts of increasing doses.
Intervention: XL309
Dose Escalation Combination Therapy
Participants will receive XL309 in sequential cohorts of increasing doses in combination with olaparib.
Intervention: XL309
Dose Escalation Combination Therapy
Participants will receive XL309 in sequential cohorts of increasing doses in combination with olaparib.
Intervention: Olaparib
Cohort Expansion Stage Single Agent Evaluation
The recommended dose as determined in the Escalation Stage will be further studied in advanced solid tumor-specific cohorts.
Intervention: XL309
Cohort Expansion Stage Combination Therapy Evaluation
The recommended dose as determined in the Escalation Stage will be further studied in combination with olaparib in advanced solid tumor-specific cohorts.
Intervention: XL309
Cohort Expansion Stage Combination Therapy Evaluation
The recommended dose as determined in the Escalation Stage will be further studied in combination with olaparib in advanced solid tumor-specific cohorts.
Intervention: Olaparib
Outcomes
Primary Outcomes
Dose Escalation Stage: Incidence of TEAEs and SAEs; AEs Leading to Dose Modification, Discontinuation, or Death; and Laboratory Abnormalities
Time Frame: Approximately 24 months
Adverse events will be recorded and severity graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Dose Escalation Stage: Incidence of Dose-Limiting Toxicities (DLTs)
Time Frame: Approximately 24 months
Dose Escalation Stage: XL309 Exposure Over Time Measured as Area Under the Plasma Concentration Curve (AUC)
Time Frame: Approximately 24 months
Dose Escalation Stage: XL309 Maximum Plasma Concentration (Cmax)
Time Frame: Approximately 24 months
Dose Escalation Stage: XL309 Time to Cmax
Time Frame: Approximately 24 months
Dose Escalation Stage: XL309 Trough Concentration (Ctrough)
Time Frame: Approximately 24 months
Lowest concentration of drug in the bloodstream, measured just before the next dose is administered.
Cohort Expansion Stage: Incidence of TEAEs and SAEs; AEs Leading to Dose Modification, Discontinuation, or Death; and Laboratory Abnormalities
Time Frame: Approximately 24 months
Adverse events will be recorded and severity graded using CTCAE version 5.0.
Dose Escalation Stage: XL309 Apparent Clearance (CL/F)
Time Frame: Approximately 24 months
Cohort Expansion Stage: Objective Response Rate (ORR)
Time Frame: Approximately 24 months
ORR will be measured per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as assessed by the Investigator. ORR for prostate cancer will be based on Prostate Cancer Working Group 3 (PCWG3) criteria, as assessed by the Investigator
Secondary Outcomes
- Dose Escalation Stage: Olaparib Ctrough at Steady State(Approximately 24 months)
- Dose Escalation Stage: Olaparib Exposure Over Time Measured as Area Under the Plasma Concentration Curve (AUC) at Steady State(Approximately 24 months)
- Dose Escalation Stage: Olaparib Cmax at Steady State(Approximately 24 months)
- Cohort Expansion Stage: Concentration of XL309 in Plasma at Specified Time Points(Approximately 24 months)
- Cohort Expansion Stage: Concentration of Olaparib in Plasma at Specified Time Points(Approximately 24 months)