Clinical trial NCT05047536: KZR-261 in Subjects With Advanced Solid Malignancies
Official title: A Phase 1 Study of KZR-261, a Small Molecule Sec61 Inhibitor, in Subjects With Advanced Solid Malignancies
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced/Metastatic Solid Tumor
Keywords: melanoma
uveal melanoma
colorectal cancer
prostate cancer
mesothelioma
Lead sponsor: Kezar Life Sciences, Inc.
Sponsor class: INDUSTRY
First posted: 2021-09-17
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Number and percentage of participants experiencing adverse events as assessed by CTCAE v5.0 (Part 1 & 2)
timeFrame: Approximately 20 months
measure: Number and percentage of participants experiencing dose-limiting toxicities as assessed by CTCAE v5.0 (Part 1)
timeFrame: Approximately 20 months
measure: Maximum plasma concentration of KZR-261 (Part 1)
timeFrame: Approximately 20 months
measure: The plasma concentration time curve of KZR-261 (Part 1)
timeFrame: Approximately 20 months
Secondary outcomes:
measure: Objective Response Rate (ORR) of KZR-261
timeFrame: Approximately 20 months
measure: Duration of response (DOR) of KZR-261
timeFrame: Approximately 20 months
measure: Progression-free Survival of Patients treated with KZR-261
timeFrame: Approximately 20 months
measure: Overall Survival of Patients treated with KZR-261
timeFrame: Approximately 20 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Cleveland
country: United States
facility: University Hospitals - Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sara Cannon Research Institution (SCRI) - Tennessee Oncology Nashville
state: Tennessee
city: San Antonio
country: United States
facility: START (South Texas Accelerated Research Therapeutics)
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists (VCS)
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
Study officials:
affiliation: Kezar Life Sciences, Inc.
name: Kezar Study Director
role: STUDY_DIRECTOR
References: