KZR-261 in Subjects With Advanced Solid Malignancies

NCT05047536 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: KZR-261-101
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 12

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 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").

Conditions

Advanced/Metastatic Solid Tumor

Keywords

melanoma; uveal melanoma; colorectal cancer; castration-resistant prostate cancer; mesothelioma

Outcome Measures

Primary Outcomes (4)

• 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

  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).

  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.

  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.

  Cycle 1: Day 1, Cycle 1: Day 15, Cycle 2: Day 1, and Cycle 2: Day 15

Secondary Outcomes (4)

• Objective Response (ORR) Following KZR-261

  20 months

• Participants With Clinical Benefit of Stable Disease Following KZR-261

  20 months

• Progression-free Survival of Participants Treated With KZR-261

  4 months and 6 months

• Overall Survival of Participants Treated With KZR-261

  20 months

Study Arms (1)

KZR-261 with standard therapy: open-label

EXPERIMENTAL

Part 1 (Dose Escalation): The initial dose cohort of the Dose Escalation received 1.8 mg/m2 of KZR-261. Participants received 3 doses in a 28-day cycle as an intravenous (IV) infusion for up to 6 cycles. \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ Part 2A (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 was to 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 * castration-resistant prostate cancer * mesothelioma Part 2B (Dose Optimization): Dose optimization in tumor-specific cohorts could have been initiated based on the totality of data after the MTD/MAD had been determined. Participants were to receive KZR-261 at the MTD/MAD or a lower clinically active dose of KZR-261.

Drug: KZR-261

Interventions

KZR-261 DRUG

KZR-261 for Injection is a lyophilized drug product supplied in single-use vials delivering 75 mg of KZR-261.

Also known as: KZR-261 for Injection

KZR-261 with standard therapy: open-label

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kezar Life Sciences, Inc.: lead

Study Sites (12)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

University Hospitals - Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Sara Cannon Research Institution (SCRI) - Tennessee Oncology Nashville

Nashville, Tennessee, 37203, United States

Location

START (South Texas Accelerated Research Therapeutics)

San Antonio, Texas, 78229, United States

Location

Virginia Cancer Specialists (VCS)

Fairfax, Virginia, 22031, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

Related Links

• Kezar Life Sciences, Inc. corporate website

MeSH Terms

Conditions

Neoplasm Metastasis; Melanoma; Uveal Melanoma; Colorectal Neoplasms; Mesothelioma

Interventions

Injections

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms, Mesothelial

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Regulatory Affairs
• Organization: Kezar Life Sciences, Inc.

clinicaltrials@kezarbio.com

650-822-5600

Study Officials

• Kezar Study Director

  Kezar Life Sciences, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: All participants received 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 participants were to be enrolled and treated with KZR-261 in Part 1 (Dose Escalation). In Part 2A (Dose Expansion), up to 175 participants (15-35 per tumor cohort \[melanoma, uveal melanoma, colorectal cancer, castration-resistant prostate cancer, mesothelioma, and "All-Tumor"\]) were to be enrolled. In Part 2B (Dose Optimization), up to 120 participants from up to 4 tumor types from the Dose Expansion were to be enrolled.

Study Record Dates

• First Submitted: September 3, 2021
• First Posted: September 17, 2021
• Study Start: September 30, 2021
• Primary Completion: January 17, 2025
• Study Completion: January 17, 2025
• Last Updated: December 19, 2025
• Results First Posted: December 19, 2025

Record last verified: 2025-12

Locations

US (12)