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Clinical Trial Record

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A Phase 1 Study of XL309 (ISM3091) Alone and in Combination in Patients With Advanced Solid Tumors

2024-04-03

2029-01-03

2029-08-03

425

Study Overview

A Phase 1 Study of XL309 (ISM3091) Alone and in Combination in Patients With Advanced Solid Tumors

This is a FIH, multicenter, open-label Phase I study to investigate the safety, tolerability, preliminary antitumor activity, as well as PK and pharmacodynamics of XL309 (previously ISM3091) administered alone or in combination with olaparib in subjects with advanced solid tumors.

N/A

  • Advanced Solid Tumor
  • DRUG: XL309 (ISM3091)
  • DRUG: Olaparib
  • XL309-101

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates Results Reporting Dates Study Record Updates

2023-06-27  

N/A  

2025-03-11  

2023-06-27  

N/A  

2025-03-13  

2023-07-06  

N/A  

2025-03  

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/ArmIntervention/Treatment
EXPERIMENTAL: Dose Escalation Single Agent Evaluation

Participants will receive XL309 once daily in sequential cohorts of increasing doses.

DRUG: XL309 (ISM3091)

  • XL309 will be administered orally once daily.
EXPERIMENTAL: Dose Escalation Combination Therapy

Participants will receive XL309 once daily in sequential cohorts of increasing dose in combination with olaparib.

DRUG: XL309 (ISM3091)

  • XL309 will be administered orally once daily.

DRUG: Olaparib

  • Olaparib administered orally twice daily.
EXPERIMENTAL: 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.

DRUG: XL309 (ISM3091)

  • XL309 will be administered orally once daily.
EXPERIMENTAL: 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.

DRUG: XL309 (ISM3091)

  • XL309 will be administered orally once daily.

DRUG: Olaparib

  • Olaparib administered orally twice daily.
Primary Outcome MeasuresMeasure DescriptionTime Frame
Dose Escalation Stage: Incidence of TEAEs, SAEs, and AEs and SAEs Leading to Dose Modification, Discontinuation, or DeathAdverse events will be recorded and severity graded using 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 Maximum Concentration (Tmax)Time to CmaxApproximately 24 months
Dose Escalation Stage: XL309 Trough Concentration (Ctrough)Lowest concentration of drug in the bloodstream, measured just before the next dose is administeredApproximately 24 months
Dose Escalation Stage: XL309 Apparent Clearance (CL/F)Approximately 24 months
Cohort Expansion Stage: Incidence of TEAEs, SAEs, AEs and SAEs Leading to Dose Modification, Discontinuation or DeathAdverse 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 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 InvestigatorApproximately 24 months
Secondary Outcome MeasuresMeasure DescriptionTime Frame
Dose Escalation Stage: Olaparib Exposure Over Time Measured as Area Under the Plasma Concentration Curve (AUC)Approximately 24 months
Dose Escalation Stage: Olaparib Maximum Plasma Concentration (Cmax)Approximately 24 months
Dose Escalation Stage: Olaparib Trough Concentration (Ctrough)Approximately 24 months
Cohort Expansion Stage: Concentration of XL309 in Plasma at Specified Time PointsApproximately 24 months
Cohort Expansion Stage: Concentration of Olaparib in Plasma at Specified Time PointsApproximately 24 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Exelixis Clinical Trials

Phone Number: 1-888-393-5494)

Email: druginfo@exelixis.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

    Key Inclusion Criteria:
    1. Capable of understanding and complying with protocol requirements. 2. Male or female aged 18 years or older. 3. Eastern Cooperative Oncology Group performance status 0 or 1. 4. Adequate bone marrow and organ function.
    Dose-Escalation Stage Single Agent and Combination:
    a) Participants whose tumor progressed, 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 HER2-negative breast cancer, with deleterious or suspected deleterious BRCA1/2 mutation, that progressed on, was intolerant to, was refused, or ineligible for (PARPi).
    ii. Histologically confirmed locally advanced/metastatic high-grade serous ovarian cancer (HGSOC), including primary peritoneal cancer (PPC) and fallopian tube cancer (FTC). Participants must have progressed on, be intolerant to, or refused PARPi therapy, if PARPi therapy is approved and available in the country where the participant is enrolled.
    iii. Histologically confirmed locally advanced/metastatic CRPC, with deleterious or suspected deleterious BRCA1/2 mutation, that progressed on, was intolerant to, refused, or ineligible for PARPi.
    iv. Histologically confirmed locally advanced/metastatic pancreatic cancer with deleterious or suspected deleterious BRCA1/2 mutation that progressed on, was intolerant to, refused, or ineligible for maintenance treatment with a PARPi.
    v. Locally advanced/metastatic tumors with deleterious or suspected deleterious germline or somatic HRR mutation or HRD phenotype.
    Cohort-Expansion Stage Single Agent and Combination:
    b) HER2-negative BRCAm Breast cancer cohort: participants with histologically confirmed locally advanced/metastatic HER2-negative Breast cancer with deleterious or suspected deleterious BRCA1/2 mutation and documented radiographic disease progression during or following their last systemic anticancer therapy and who progressed on, was intolerant to, refused, or was ineligible for treatment with a PARPi.
    c) Platinum-resistant HGSOC cohort: i. Participants with histologically confirmed locally advanced/metastatic HGSOC, including primary peritoneal cancer (PPC) and fallopian tube cancer (FTC), and who progressed on, was intolerant to, refused, or was ineligible for maintenance treatment with a PARPi and who have platinum-resistant disease, defined by platinum free interval of less than 6 months.
    ii. Platinum-refractory disease (progression on first-line treatment or within 4 weeks of completion) are excluded.
    d) Platinum-sensitive HGSOC cohort - expansion combination only: histologically confirmed locally advanced/metastatic HGSOC, including PPC and FTC, that progressed on, refused, or ineligible to maintenance treatment with a PARPi, and who have platinum-sensitive disease, defined by platinum free interval of more than 6 months.
    e) mCRPC cohort: participants with metastatic, castration-resistant adenocarcinoma of the prostate with deleterious or suspected deleterious BRCA1/2 mutation, that progressed on, or was intolerant, refused, or ineligible to PARPi.
    f) HRRm advanced solid tumors cohort: participants with locally advanced/metastatic tumors with deleterious or suspected deleterious germline or somatic HRR mutation or HRD phenotype.
    For all participants with solid tumors: 5. Participants in the Cohort-Expansion Stage must have at least 1 measurable target lesion. 6. Recovery to baseline or ≤ Grade 1 CTCAE v5 from AE(s) related to any prior treatments.
    Key Exclusion Criteria
    1. Prior anticancer treatment including:
    1. Small molecule-targeted therapy < 5 half-lives from first dose of study treatment, or 3 weeks (whichever is shorter). 2. Any antibody therapy < 5 half-lives from first dose of study treatment (or 4 weeks since last therapy, whichever is shorter). 3. 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. 4. 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. 2. 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. 3. 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. 4. Lactating or pregnant females. 5. Clinically relevant cardiovascular disease. 6. Known history of myelodysplastic syndrome. 7. 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. 8. Inability or unwillingness to comply with requirement for oral drug administration or presence of a gastrointestinal condition that would preclude adequate absorption of XL309.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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