KZR-261 in Subjects With Advanced Solid Malignancies

A Phase 1 Study of KZR-261, a Small Molecule Sec61 Inhibitor, in Subjects With Advanced Solid Malignancies

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").

Study Overview

• Status: Recruiting
• Conditions: Advanced/Metastatic Solid Tumor
• Intervention / Treatment: Drug: KZR-261

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 Type: Interventional
• Enrollment (Estimated): 225
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Operations; Phone Number: 650-822-5600; Email: clinicaltrials@kezarbio.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars Sinai Medical Center
      • Principal Investigator: Alain Mita, MD
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California Los Angeles
      • Principal Investigator: Bartosz Chmielowski, MD, PhD
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Principal Investigator: Tiago Biachi de Castria, MD, PhD
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Winship Cancer Institute of Emory University
      • Principal Investigator: R. Donald Harvey, Pharm D
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospitals - Cleveland Medical Center
      • Principal Investigator: Amit Mahipal, MD
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Recruiting
      • Fox Chase Cancer Center
      • Principal Investigator: Anthony Olszanski, MD
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sara Cannon Research Institution (SCRI) - Tennessee Oncology Nashville
      • Principal Investigator: Meredith McKean, MD
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • START (South Texas Accelerated Research Therapeutics)
      • Principal Investigator: Kyriakos Papadopoulos, MD
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists (VCS)
      • Principal Investigator: Alexander Spira, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: KZR-261 for Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Approximately 20 months
Number and percentage of participants experiencing dose-limiting toxicities as assessed by CTCAE v5.0 (Part 1)	Incidence and percentage of dose-limiting toxicities will be collected from start of enrollment	Approximately 20 months
Maximum plasma concentration of KZR-261 (Part 1)	Summary of maximum plasma concentration (Cmax) will be assessed	Approximately 20 months
The plasma concentration time curve of KZR-261 (Part 1)	Summary of the plasma concentration time curve (AUC) will be assessed	Approximately 20 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) of KZR-261	Defined as the rate of partial responses (PRs) plus complete responses (CRs) according to RECIST v1.1	Approximately 20 months
Duration of response (DOR) of KZR-261	Duration of overall response (partial response and complete response)	Approximately 20 months
Progression-free Survival of Patients treated with KZR-261	Time to disease progression	Approximately 20 months
Overall Survival of Patients treated with KZR-261	Time of overall survival	Approximately 20 months

Collaborators and Investigators

• Sponsor: Kezar Life Sciences, Inc.
• Investigators: Study Director: Kezar Study Director, Kezar Life Sciences, Inc.

Publications and helpful links

Helpful Links

• Kezar Life Sciences, Inc. corporate website

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2021
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: September 3, 2021
• First Submitted That Met QC Criteria: September 11, 2021
• First Posted (Actual): September 17, 2021

Study Record Updates

• Last Update Posted (Estimated): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: colorectal cancer; prostate cancer; mesothelioma; melanoma; uveal melanoma
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: KZR-261-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No