A Phase 1 Study of XL309 (ISM3091) Alone and in Combination in Participants With Advanced Solid Tumors
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
1 other identifier
interventional
429
1 country
16
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Apr 2024
Longer than P75 for phase_1
16 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 27, 2023
CompletedFirst Posted
Study publicly available on registry
July 6, 2023
CompletedStudy Start
First participant enrolled
April 3, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 3, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 3, 2029
September 5, 2025
August 1, 2025
4.8 years
June 27, 2023
August 28, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (9)
Dose Escalation Stage: Incidence of TEAEs and SAEs; AEs Leading to Dose Modification, Discontinuation, or Death; and Laboratory Abnormalities
Adverse events will be recorded and severity graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Approximately 24 months
Dose Escalation Stage: Incidence of Dose-Limiting Toxicities (DLTs)
Approximately 24 months
Dose Escalation Stage: XL309 Exposure Over Time Measured as Area Under the Plasma Concentration Curve (AUC)
Approximately 24 months
Dose Escalation Stage: XL309 Maximum Plasma Concentration (Cmax)
Approximately 24 months
Dose Escalation Stage: XL309 Time to Cmax
Approximately 24 months
Dose Escalation Stage: XL309 Trough Concentration (Ctrough)
Lowest concentration of drug in the bloodstream, measured just before the next dose is administered.
Approximately 24 months
Dose Escalation Stage: XL309 Apparent Clearance (CL/F)
Approximately 24 months
Cohort Expansion Stage: Incidence of TEAEs and SAEs; AEs Leading to Dose Modification, Discontinuation, or Death; and Laboratory Abnormalities
Adverse events will be recorded and severity graded using CTCAE version 5.0.
Approximately 24 months
Cohort Expansion Stage: Objective Response Rate (ORR)
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
Approximately 24 months
Secondary Outcomes (5)
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
Dose Escalation Stage: Olaparib Ctrough 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
Study Arms (4)
Dose Escalation Single Agent Evaluation
EXPERIMENTALParticipants will receive XL309 in sequential cohorts of increasing doses.
Dose Escalation Combination Therapy
EXPERIMENTALParticipants will receive XL309 in sequential cohorts of increasing doses in combination with olaparib.
Cohort Expansion Stage Single Agent Evaluation
EXPERIMENTALThe recommended dose as determined in the Escalation Stage will be further studied in advanced solid tumor-specific cohorts.
Cohort Expansion Stage Combination Therapy Evaluation
EXPERIMENTALThe recommended dose as determined in the Escalation Stage will be further studied in combination with olaparib in advanced solid tumor-specific cohorts.
Interventions
XL309 will be administered orally per assigned schedule.
Olaparib will be administered orally per assigned schedule.
Eligibility Criteria
You may qualify if:
- Capable of understanding and complying with protocol requirements.
- Male or female aged 18 years or older.
- Eastern Cooperative Oncology Group performance status 0 or 1.
- 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.
- iv. Histologically confirmed locally advanced/metastatic pancreatic cancer with deleterious or suspected deleterious BRCA1/2 alteration.
- v. Locally advanced/metastatic tumors with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) mutation or homologous recombination deficiency (HRD) phenotype.
- Cohort-Expansion Stage Single Agent and Combination:
- b) HER2-negative breast cancer cohort: participants with histologically confirmed locally advanced/metastatic (HER2)-negative breast cancer with alterations in select HRR genes.
- c) Platinum-sensitive HGSOC cohort: participants with histologically confirmed locally advanced/metastatic HGSOC, including primary peritoneal cancer (PPC) and fallopian tube cancer (FTC), with positive HRD result using an approved diagnostic, and/or alterations in select HRR genes.
- +5 more criteria
You may not qualify if:
- Prior anticancer treatment including:
- Small molecule-targeted therapy \< 5 half-lives from first dose of study treatment, or 3 weeks (whichever is shorter).
- Any antibody therapy \< 5 half-lives from first dose of study treatment (or 4 weeks since last therapy, whichever is shorter).
- Chemotherapy with nitrosoureas or mitomycin C \< 6 weeks from first dose of study treatment. Other chemotherapy \< 3 weeks prior to first dose of study treatment.
- Radiation therapy (including radiofrequency ablation) \< 1 week prior to initiation of study treatment. Participants with clinically relevant ongoing complications from prior radiation therapy are not eligible.
- Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment.
- History of hypersensitivity to any excipient of XL309, or history of allergic reactions attributed to drugs with a similar chemical or biologic structure or class to XL309.
- Lactating or pregnant females.
- Clinically relevant cardiovascular disease.
- Known history of myelodysplastic syndrome.
- Other severe, acute, or chronic medical condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or that may interfere with the interpretation of the study results, and in the judgment of the investigator, would make the participant inappropriate for the study.
- Inability or unwillingness to comply with requirement for oral drug administration or presence of a gastrointestinal condition that would preclude adequate absorption of XL309.
- Prior treatment with a ubiquitin specific peptidase 1 (USP1) inhibitor.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Exelixislead
Study Sites (16)
Exelixis Clinical Site #12
Fountain Valley, California, 92708, United States
Exelixis Clinical Site #15
Jacksonville, Florida, 32224, United States
Exelixis Clinical Site #8
Orlando, Florida, 32827, United States
Exelixis Clinical Site #16
Tampa, Florida, 33612, United States
Exelixis Clinical Site #14
Rochester, Minnesota, 55905, United States
Exelixis Clinical Site #10
Kansas City, Missouri, 64111, United States
Exelixis Clinical Site #9
New Brunswick, New Jersey, 08901, United States
Exelixis Clinical Site #5
New York, New York, 10029, United States
Exelixis Clinical Site #7
Cleveland, Ohio, 44106, United States
Exelixis Clinical Site #13
Oklahoma City, Oklahoma, 73104, United States
Exelixis Clinical Site #11
Germantown, Tennessee, 38138, United States
Exelixis Clinical Site #6
Nashville, Tennessee, 37203, United States
Exelixis Clinical Site #4
Austin, Texas, 78758, United States
Exelixis Clinical Site #1
Houston, Texas, 77030, United States
Exelixis Clinical Site #2
Houston, Texas, 77030, United States
Exelixis Clinical Site #3
San Antonio, Texas, 78229, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 27, 2023
First Posted
July 6, 2023
Study Start
April 3, 2024
Primary Completion (Estimated)
January 3, 2029
Study Completion (Estimated)
August 3, 2029
Last Updated
September 5, 2025
Record last verified: 2025-08