KZR-261 in Subjects With Advanced Solid Malignancies
- Conditions
- Advanced/Metastatic Solid Tumor
- Interventions
- Drug: KZR-261
- Registration Number
- NCT05047536
- Lead Sponsor
- Kezar Life Sciences, Inc.
- 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").
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 61
- 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).
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description KZR-261 with standard therapy: open-label KZR-261 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
- Primary Outcome Measures
Name Time Method Number and percentage of participants experiencing dose-limiting toxicities as assessed by CTCAE v5.0 (Part 1) Approximately 20 months Incidence and percentage of dose-limiting toxicities will be collected from start of enrollment
Maximum plasma concentration of KZR-261 (Part 1) Approximately 20 months Summary of maximum plasma concentration (Cmax) will be assessed
The plasma concentration time curve of KZR-261 (Part 1) Approximately 20 months Summary of the plasma concentration time curve (AUC) will be assessed
Number and percentage of participants experiencing adverse events as assessed by CTCAE v5.0 (Part 1 & 2) Approximately 20 months Incidence and percentage of adverse events and serious adverse events will be collected from start of enrollment
- Secondary Outcome Measures
Name Time Method Overall Survival of Patients treated with KZR-261 Approximately 20 months Time of overall survival
Objective Response Rate (ORR) of KZR-261 Approximately 20 months Defined as the rate of partial responses (PRs) plus complete responses (CRs) according to RECIST v1.1
Duration of response (DOR) of KZR-261 Approximately 20 months Duration of overall response (partial response and complete response)
Progression-free Survival of Patients treated with KZR-261 Approximately 20 months Time to disease progression
Trial Locations
- Locations (12)
START (South Texas Accelerated Research Therapeutics)
🇺🇸San Antonio, Texas, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
Sara Cannon Research Institution (SCRI) - Tennessee Oncology Nashville
🇺🇸Nashville, Tennessee, United States
University of California Los Angeles
🇺🇸Los Angeles, California, United States
University Hospitals - Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
Virginia Cancer Specialists (VCS)
🇺🇸Fairfax, Virginia, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States