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KZR-261 in Subjects With Advanced Solid Malignancies

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: NCT05047536
Recruitment Status : Recruiting
First Posted : September 17, 2021
Last Update Posted : March 6, 2023
Sponsor:
Information provided by (Responsible Party):
Kezar Life Sciences, Inc.

Study Description
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Brief Summary:
A first-in-human, open-label, multicenter, Phase 1 study of KZR-261 designed to assess the safety and tolerability, preliminary anti-tumor activity, and pharmacokinetics (PK) of KZR-261, as well as identify the recommended Phase 2 dose (RP2D). The study comprises a Part 1 (Dose Escalation) and a Part 2 (Dose Expansion) in solid organ tumors (melanoma/uveal melanoma, mesothelioma, colorectal cancer, prostate cancer, and "All-Tumors").

Condition or disease Intervention/treatment Phase
Advanced/Metastatic Solid Tumor Drug: KZR-261 Phase 1

Detailed Description:

The first-in-human, open-label, multicenter, Phase 1 study of KZR-261, Study KZR-261-101, will be conducted in two parts (dose escalation and dose expansion) to evaluate the safety and tolerability, pharmacokinetics, pharmacodynamics, and evaluate the preliminary anti-tumor activity of KZR-261 in subjects with locally advanced or metastatic solid malignancies for whom no therapeutics are available that can confer a reasonable likelihood of clinical benefit. The 5 tumor cohorts in the dose expansion part include advanced malignant:

  • melanoma/uveal melanoma
  • mesothelioma
  • colorectal cancer
  • castrate-resistant prostate cancer
  • "All-Tumors"

Part 1 (Dose Escalation) and Part 2 (Dose Expansion) comprise a 4-week Screening Period, a Treatment Period lasting approximately 24 weeks, 4-6-week Safety Follow-up, and a 12-month Long-Term Follow-up Period (after last dose of study treatment), for a total study duration of approximately 20 months.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 225 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

All subjects will receive 30 to 60-minute intravenous infusion of KZR-261 via a central line on Days 1, 8, and 15 of a 4-week (28-day) treatment cycle.

Up to approximately 50 subjects will be enrolled and treated with KZR-261 in Part 1 (Dose Escalation). In Part 2 (Dose Expansion), up to 175 subjects (15-35 per tumor cohort [melanoma, uveal melanoma, colorectal cancer, prostate cancer, mesothelioma, and "All-Tumor"]) will be enrolled.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of KZR-261, a Small Molecule Sec61 Inhibitor, in Subjects With Advanced Solid Malignancies
Actual Study Start Date : September 30, 2021
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : October 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: KZR-261 with standard therapy: open-label

Part 1 (Dose Escalation)

The initial dose cohort of the Dose Escalation will receive 1.8 mg/m2 of KZR-261. Subjects will receive 3 doses in a 28-day cycle.

___________________________________________

Part 2 (Dose Expansion)

Following safety review of all Dose Escalation cohorts and determination of the maximum tolerated dose (MTD) or maximum administered dose (MAD), KZR-261 will be evaluated for safety and preliminary efficacy in 4 tumor-specific cohorts and 1 all-tumor cohort to determine the recommended phase 2 dose (RP2D). The 4 tumor-specific cohorts will include:

  • melanoma (including uveal melanoma)
  • colorectal cancer
  • prostate cancer
  • mesothelioma
 Drug: KZR-261
KZR-261 for Injection is a lyophilized drug product supplied in single-use vials delivering 75 mg of KZR-261.
Other Name: KZR-261 for Injection


Outcome Measures
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Primary Outcome Measures :
  1. Number and percentage of participants experiencing adverse events as assessed by CTCAE v5.0 (Part 1 & 2) [ Time Frame: Approximately 20 months ]
    Incidence and percentage of adverse events and serious adverse events will be collected from start of enrollment

  2. Number and percentage of participants experiencing dose-limiting toxicities as assessed by CTCAE v5.0 (Part 1) [ Time Frame: Approximately 20 months ]
    Incidence and percentage of dose-limiting toxicities will be collected from start of enrollment

  3. Maximum plasma concentration of KZR-261 (Part 1) [ Time Frame: Approximately 20 months ]
    Summary of maximum plasma concentration (Cmax) will be assessed

  4. The plasma concentration time curve of KZR-261 (Part 1) [ Time Frame: Approximately 20 months ]
    Summary of the plasma concentration time curve (AUC) will be assessed


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) of KZR-261 [ Time Frame: Approximately 20 months ]
    Defined as the rate of partial responses (PRs) plus complete responses (CRs) according to RECIST v1.1

  2. Duration of response (DOR) of KZR-261 [ Time Frame: Approximately 20 months ]
    Duration of overall response (partial response and complete response)

  3. Progression-free Survival of Patients treated with KZR-261 [ Time Frame: Approximately 20 months ]
    Time to disease progression

  4. Overall Survival of Patients treated with KZR-261 [ Time Frame: Approximately 20 months ]
    Time of overall survival


Eligibility Criteria
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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:

  • Histologic or cytologic evidence of malignant solid tumor with advanced disease (except primary central nervous system [CNS] neoplasms), defined as cancer that is either metastatic or locally advanced and unresectable (and for which additional radiation therapy or other locoregional therapies are not considered to result in reasonable clinical benefit).
  • Disease that is resistant to or relapsed following available standard systemic therapy, or for which there is no standard systemic therapy or reasonable therapy in the Investigator's judgement likely to result in clinical benefit, or if such therapy has been refused by the subject. Documentation of the reason must be provided for subjects who have not received a standard therapy likely to result in clinical benefit.
  • Eastern Cooperative Oncology Group Performance Status score of 0 or 1.
  • Adequate baseline hematologic and organ function.
  • Willing to use contraception.

Additional Inclusion for Part 2: Histologic or cytologic evidence of malignancy (melanoma/uveal melanoma, colorectal cancer, prostate cancer, mesothelioma).

Exclusion Criteria:

  • Subjects who have participated in Part 1 dose escalation are not eligible to enroll in Part 2 dose expansion.
  • Persistent clinically significant toxicities from previous anticancer therapy (excluding alopecia).
  • Treatment with cytotoxic, biologic, or targeted therapies for advanced cancer within 14 days before administration of the subject's first dose of KZR-261.
  • Treatment with an investigational drug within 28 days before administration of the subject's first dose of KZR-261.
  • Radiation therapy within 14 days of before administration of the subject's first dose of KZR-261.
  • Major surgical procedure within 28 days before administration of the subject's first dose of KZR-261.
  • History of risk factors for Torsades de pointes.
  • Active, symptomatic CNS metastases or primary CNS malignancy.
  • Any female who is breastfeeding or who plans to become pregnant during the study, or who are actively trying to conceive at the time of signing of the informed consent form (ICF).
  • Uncontrolled, clinically significant pulmonary disease.
Contacts and Locations
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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): NCT05047536


Contacts
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Contact: Clinical Operations 650-822-5600 clinicaltrials@kezarbio.com

Locations
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United States, California
Cedars Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
United States, Georgia
Winship Cancer Institute of Emory University Recruiting
Atlanta, Georgia, United States, 30322
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
United States, Tennessee
Sara Cannon Research Institution (SCRI) - Tennessee Oncology Nashville Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
START (South Texas Accelerated Research Therapeutics) Recruiting
San Antonio, Texas, United States, 78229
United States, Virginia
Virginia Cancer Specialists (VCS) Recruiting
Fairfax, Virginia, United States, 22031
Sponsors and Collaborators
Kezar Life Sciences, Inc.
Investigators
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Study Director: Kezar Study Director Kezar Life Sciences, Inc.
More Information
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Additional Information:

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Responsible Party: Kezar Life Sciences, Inc.
ClinicalTrials.gov Identifier: NCT05047536    
Other Study ID Numbers: KZR-261-101
First Posted: September 17, 2021    Key Record Dates
Last Update Posted: March 6, 2023
Last Verified: March 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kezar Life Sciences, Inc.:
melanoma
uveal melanoma
colorectal cancer
prostate cancer
mesothelioma
Additional relevant MeSH terms:
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Neoplasms