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 comprised a Part 1 (Dose Escalation) and a Part 2 (2A Dose Expansion and 2B Dose Optimization) in solid organ tumors (melanoma/uveal melanoma, mesothelioma, colorectal cancer, castration-resistant prostate cancer, and "All-Tumors").
The first-in-human, open-label, multicenter, Phase 1 study of KZR-261, Study KZR-261-101, was 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 participants with locally advanced or metastatic solid malignancies for whom no therapeutics are available (or available therapeutics were refused) 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 * castration-resistant prostate cancer * "All-Tumors" (other advanced solid malignancies) Part 1 (Dose Escalation) and Part 2 (2A Dose Expansion and 2B Dose Optimization) comprised 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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
61
KZR-261 for Injection is a lyophilized drug product supplied in single-use vials delivering 75 mg of KZR-261.
Cedars Sinai Medical Center
Los Angeles, California, United States
University of California Los Angeles
Los Angeles, California, United States
Moffitt Cancer Center
Tampa, Florida, United States
Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)
Incidence and percentage of adverse events and serious adverse events will be collected from start of enrollment
Time frame: 20 months
Number and Percentage of Participants Experiencing Dose-limiting Toxicities
Number and percentage of participants experiencing dose-limiting toxicities (DLT) collected from start of enrollment through the first 28 days of Cycle 1 as assessed by CTCAE v5.0 (Part 1).
Time frame: 28 days
Maximum Plasma Concentration of KZR-261 (Part 1)
This is the maximum observed plasma concentration (Cmax) observed after administration of KZR-261 in Cycle 1 (Days 1 and 15) and Cycle 2 (Days 1 and 15). The PK parameters were calculated using all timepoints at which the concentration was measured, ie. predose, 15 minutes post start of infusion, end of infusion, and 5, 15, 30 minutes, 1, 2, 4, 6, 24, 48, and 96 hours post infusion.
Time frame: Cycle 1: Day 1, Cycle 1: Day 15, Cycle 2: Day 1, and Cycle 2: Day 15
The Plasma Concentration Time Curve of KZR-261 (Part 1)
This is the area under the curve (AUC) from predose through postdose observed after administration of KZR-261 in Cycle 1 (Days 1 and 15) and Cycle 2 (Days 1 and 15). The PK parameters were calculated using all timepoints at which the concentration was measured, ie. predose, 15 minutes post start of infusion, end of infusion, and 5, 15, 30 minutes, 1, 2, 4, 6, and 24 hours post infusion.
Time frame: Cycle 1: Day 1, Cycle 1: Day 15, Cycle 2: Day 1, and Cycle 2: Day 15
Objective Response (ORR) Following KZR-261
The objective response following KZR-261 defined as a best overall response of Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. A CR is defined as the disappearance of all target lesions and a PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of longest lesion diameters.
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Winship Cancer Institute of Emory University
Atlanta, Georgia, United States
Henry Ford Health System
Detroit, Michigan, United States
University Hospitals - Cleveland Medical Center
Cleveland, Ohio, United States
Cleveland Clinic
Cleveland, Ohio, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
Sara Cannon Research Institution (SCRI) - Tennessee Oncology Nashville
Nashville, Tennessee, United States
START (South Texas Accelerated Research Therapeutics)
San Antonio, Texas, United States
...and 2 more locations
Time frame: 20 months
Participants With Clinical Benefit of Stable Disease Following KZR-261
The clinical benefit rate defined as the number of participants achieving a best response of complete response (CR)/partial response (PR) or stable disease over at least 2 consecutive response assessment time points. Stable disease is defined as neither sufficient decrease to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of longest diameters of target lesions while on study.
Time frame: 20 months
Progression-free Survival of Participants Treated With KZR-261
The number of participants with progression-free survival (PFS), defined as the date of initiation of study treatment to the date of documented PD or death from any cause, whichever occurs first, at 4 months and 6 months. PFS is based on the number of subjects in each group in the response evaluable population at the specific timepoints (4 or 6 months).
Time frame: 4 months and 6 months
Overall Survival of Participants Treated With KZR-261
Time of overall survival for participants treated with KZR-261.
Time frame: 20 months