NCT05047536 · REGISTRY CONDITION SEARCH

KZR-261 in Subjects With Advanced Solid Malignancies

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1
Status at capture: TERMINATED
Registry last update: 2025-12-19

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").

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)

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outcome · POSTED

Number and Percentage of Participants Experiencing Dose-limiting Toxicities

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outcome · POSTED

Maximum Plasma Concentration of KZR-261 (Part 1)

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outcome · POSTED

The Plasma Concentration Time Curve of KZR-261 (Part 1)

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outcome · POSTED

Objective Response (ORR) Following KZR-261

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outcome · POSTED

Participants With Clinical Benefit of Stable Disease Following KZR-261

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outcome · POSTED

Progression-free Survival of Participants Treated With KZR-261

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outcome · POSTED

Overall Survival of Participants Treated With KZR-261

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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, castration-resistant 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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Drug: KZR-261
label
KZR-261 with standard therapy: open-label
type
EXPERIMENTAL

interventions

arm Group Labels
KZR-261 with standard therapy: open-label
description
KZR-261 for Injection is a lyophilized drug product supplied in single-use vials delivering 75 mg of KZR-261.
name
KZR-261
other Names
KZR-261 for Injection
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

intervention Model Description

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.

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 61
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Incidence and percentage of adverse events and serious adverse events will be collected from start of enrollment
measure
Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)
time Frame
20 months
description
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).
measure
Number and Percentage of Participants Experiencing Dose-limiting Toxicities
time Frame
28 days
description
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.
measure
Maximum Plasma Concentration of KZR-261 (Part 1)
time Frame
Cycle 1: Day 1, Cycle 1: Day 15, Cycle 2: Day 1, and Cycle 2: Day 15
description
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.
measure
The Plasma Concentration Time Curve of KZR-261 (Part 1)
time Frame
Cycle 1: Day 1, Cycle 1: Day 15, Cycle 2: Day 1, and Cycle 2: Day 15

secondary Outcomes

description
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.
measure
Objective Response (ORR) Following KZR-261
time Frame
20 months
description
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.
measure
Participants With Clinical Benefit of Stable Disease Following KZR-261
time Frame
20 months
description
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).
measure
Progression-free Survival of Participants Treated With KZR-261
time Frame
4 months and 6 months
description
Time of overall survival for participants treated with KZR-261.
measure
Overall Survival of Participants Treated With KZR-261
time Frame
20 months

Full study description

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").
detailed Description: 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.

Source references