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Study of XL309 (ISM3091) in Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05932862
Recruitment Status : Recruiting
First Posted : July 6, 2023
Last Update Posted : February 7, 2024
Sponsor:
Information provided by (Responsible Party):
Exelixis

Brief Summary:
This is a first-in-human, multicenter, open-label Phase 1 study evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of XL309 in patients with advanced homologous recombination deficient [HRD] solid tumors.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: XL309 (ISM3091) Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 66 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of XL309 (ISM3091) in Patients With Advanced Solid Tumors
Actual Study Start Date : August 17, 2023
Estimated Primary Completion Date : July 27, 2024
Estimated Study Completion Date : December 9, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 1 - Dose Escalation
Patients will receive XL309 once daily in sequential cohorts of increasing doses.
Drug: XL309 (ISM3091)
XL309 will be administered orally once daily.

Experimental: Part 2 - Dose optimization
Participants will be randomized to receive one of the two selected dose levels of XL309 once daily determined by Study Review Committee.
Drug: XL309 (ISM3091)
XL309 will be administered orally once daily.




Primary Outcome Measures :
  1. Number of participants with treatment-emergent adverse events (TEAEs) and Serious Adverse events (SAEs) [ Time Frame: Approximately 1 year ]
    To assess the safety and tolerability of XL309.

  2. Number of participants with dose-limiting toxicity (DLTs) [ Time Frame: Cycle 1 (each cycle is 28 days) ]
    To assess the safety and tolerability of XL309. DLTs will be measured only during the dose escalation part.


Secondary Outcome Measures :
  1. Area under the plasma concentration-time curve from time zero to time t (AUC0-t) [ Time Frame: Cycle1- Cycle 6 (each cycle is 28 days) ]
    To characterize the PK of XL309 following a single dose administration and at a steady state after multiple dosing.

  2. Maximum observed concentration (Cmax) [ Time Frame: Cycle1- Cycle 6 (each cycle is 28 days) ]
    To characterize the PK of XL309 following a single dose administration and at a steady state after multiple dosing.

  3. Time to reach maximum plasma concentration (Tmax) [ Time Frame: Cycle1- Cycle 6 (each cycle is 28 days) ]
    To characterize the PK of XL309 following a single dose administration and at a steady state after multiple dosing.

  4. Apparent terminal elimination half-life (t1/2) [ Time Frame: Cycle1- Cycle 6 (each cycle is 28 days) ]
    To characterize the PK of XL309 following a single dose administration and at a steady state after multiple dosing.

  5. Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUCinf) [ Time Frame: Cycle1- Cycle 6 (each cycle is 28 days) ]
    To characterize the PK of XL309 following a single dose administration and at a steady state after multiple dosing.

  6. AUC from time zero to the time of the dosing interval (AUC0-τ) [ Time Frame: Cycle1- Cycle 6 (each cycle is 28 days) ]
    To characterize the PK of XL309 following a single dose administration and at a steady state after multiple dosing

  7. Accumulation ratio (AR) [ Time Frame: Cycle1- Cycle 6 (each cycle is 28 days) ]
    To characterize the PK of XL309 following a single dose administration and at a steady state after multiple dosing.

  8. Apparent total body clearance of drug (CL/F) [ Time Frame: Cycle1- Cycle 6 (each cycle is 28 days) ]
    To characterize the PK of XL309 following a single dose administration and at a steady state after multiple dosing.

  9. Apparent volume of distribution associated with the terminal phase (Vz/F) [ Time Frame: Cycle1- Cycle 6 (each cycle is 28 days) ]
    To characterize the PK of XL309 following a single dose administration and at a steady state after multiple dosing.

  10. Overall response rate (ORR) [ Time Frame: Approximately 1 year ]
    ORR defined as the proportion of patients with a best overall response of either complete response (CR) or partial response (PR). ORR will be calculated based on disease status evaluated by the investigator according to Prostate Cancer Working Group 3 (PCWG3) for prostate cancer and Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for all other tumors.

  11. Duration of Response (DoR) [ Time Frame: Approximately 1 year ]
    DoR defined as the time between the date of first response and the date of disease progression or death, whichever occurs first, will be computed for patients with a response (CR or PR).

  12. Progression Free Survival (PFS) [ Time Frame: Approximately 1 year ]
    PFS defined as the time between date of first dose of XL309 and date of progression according to Prostate Cancer Working Group 3 (PCWG3) or Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death.

  13. Overall survival (OS) [ Time Frame: Approximately 1 year ]
    OS defined as length of time from the first dose of XL309 to the date of death, regardless of the cause of death, will be computed for all treated patients with measurable disease at baseline. Overall survival will be measured according to PCWG3 for prostate cancer and RECIST version 1.1 for all other tumors.

  14. Number of participants with Prostate specific antigen (PSA) response [ Time Frame: Approximately 1 year ]
    To assess the preliminary antitumor activity of XL309

  15. Time-to-PSA progression [ Time Frame: Approximately 1 year ]
    To assess the preliminary antitumor activity of XL309



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient should understand, sign, and date the written informed consent form (ICF) prior to screening
  • Male or female aged 18 years or older
  • All participants must have documented BRCA 1/2 mutant and progressed on, or was intolerant to, poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi) or have HRD+ in solid tumor, which is identified through a validated sequencing test
  • Eastern Cooperative Oncology Group performance status 0, 1, or 2
  • Life expectancy ≥ 3 months
  • Adequate bone marrow and organ function at study entry

Exclusion Criteria:

  • Prior anticancer treatment includes:

    1. Chemotherapy or small molecule-targeted therapy < 3 weeks prior to first dose of study treatment.
    2. Any antibody therapy < 5 half-lives from first dose of study treatment (or 4 weeks since last therapy, whichever is the shortest).
    3. Chemotherapy with nitrosoureas or mitomycin C < 6 weeks from first dose of study treatment.
    4. Invasive surgery requiring general anesthesia < 4 weeks from first dose of study treatment.
    5. Radiation therapy (including radiofrequency ablation) < 4 weeks prior to initiation of study treatment.
  • Any Cardiac disease as per Protocol.
  • Active infection with human immunodeficiency virus (HIV) or hepatitis B virus or hepatitis C virus.
  • Patients with known history of myelodysplastic syndrome.
  • Any unresolved toxicities from prior therapy greater than NCI-CTCAE version 5.0 Grade 1 or that have not resolved to baseline at the time of starting study. Exceptions include alopecia, peripheral neuropathy, and, upon discussion with and approval by the medical monitor, other toxicities that are not thought to present a risk to patient safety.
  • 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 judgement of the investigator, would make the patient inappropriate for the study.
  • Patient inability or unwillingness to comply with requirement for oral drug administration or presence of a gastrointestinal condition.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05932862


Contacts
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Contact: Exelixis Clinical Trials 1-888-393-5494) druginfo@exelixis.com

Locations
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United States, Texas
Exelixis Clinical Site 101 Recruiting
Houston, Texas, United States, 77030
Exelixis Clinical Site 102 Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Exelixis
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Responsible Party: Exelixis
ClinicalTrials.gov Identifier: NCT05932862    
Other Study ID Numbers: XL309-101
First Posted: July 6, 2023    Key Record Dates
Last Update Posted: February 7, 2024
Last Verified: February 2024

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Exelixis:
breast cancers
ovarian cancer
prostate cancer
ubiquitin specific peptidase 1 (USP1)
Advanced HRD Solid Tumors
Additional relevant MeSH terms:
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Neoplasms