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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

Status
Terminated
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT05047536
Enrollment
61
Registered
2021-09-17
Start date
2021-09-30
Completion date
2025-01-17
Last updated
2025-12-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Advanced/Metastatic Solid Tumor

Keywords

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

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.

Interventions

DRUGKZR-261

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

Sponsors

Kezar Life Sciences, Inc.
Lead SponsorINDUSTRY

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

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.

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

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.

Design outcomes

Primary

MeasureTime frameDescription
The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 1: Day 1, Cycle 1: Day 15, Cycle 2: Day 1, and Cycle 2: Day 15This 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.
Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)20 monthsIncidence and percentage of adverse events and serious adverse events will be collected from start of enrollment
Number and Percentage of Participants Experiencing Dose-limiting Toxicities28 daysNumber 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).
Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 1: Day 1, Cycle 1: Day 15, Cycle 2: Day 1, and Cycle 2: Day 15This 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.

Secondary

MeasureTime frameDescription
Objective Response (ORR) Following KZR-26120 monthsThe 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.
Participants With Clinical Benefit of Stable Disease Following KZR-26120 monthsThe 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.
Progression-free Survival of Participants Treated With KZR-2614 months and 6 monthsThe 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).
Overall Survival of Participants Treated With KZR-26120 monthsTime of overall survival for participants treated with KZR-261.

Countries

United States

Participant flow

Recruitment details

At the time of study termination, Part 2A of the study had only enrolled participants with melanomas. Part 2B of the study (Dose Optimization) did not occur.

Participants by arm

ArmCount
Dose 1
Participants received 1.8 mg/m\^2 of KZR-261. Participants received 3 doses in a 28-day cycle as an intravenous (IV) infusion for up to six cycles.
2
Dose 2
Participants received 3.6 mg/m\^2 of KZR-261. Participants received 3 doses in a 28-day cycle as an intravenous (IV) infusion for up to six cycles.
2
Dose 3
Participants received 7.2 mg/m\^2 of KZR-261. Participants received 3 doses in a 28-day cycle as an intravenous (IV) infusion for up to six cycles.
2
Dose 4
Participants received 12 mg/m\^2 of KZR-261. Participants received 3 doses in a 28-day cycle as an intravenous (IV) infusion for up to six cycles.
6
Dose 5
Participants received 18 mg/m\^2 of KZR-261. Participants received 3 doses in a 28-day cycle as an intravenous (IV) infusion for up to six cycles.
6
Dose 6
Participants received 27 mg/m\^2 of KZR-261. Participants received 3 doses in a 28-day cycle as an intravenous (IV) infusion for up to six cycles.
6
Dose 7
Participants received 40 mg/m\^2 of KZR-261. Participants received 3 doses in a 28-day cycle as an intravenous (IV) infusion for up to six cycles.
5
Dose 8
Participants received 60 mg/m\^2 of KZR-261. Participants received 3 doses in a 28-day cycle as an intravenous (IV) infusion for up to six cycles.
17
Dose 9
Participants received 80 mg/m\^2 of KZR-261. Participants received 3 doses in a 28-day cycle as an intravenous (IV) infusion for up to six cycles.
8
Melanoma Expansion Cohort
Participants received 60 mg/m\^2 of KZR-261. Participants received 3 doses in a 28-day cycle as an intravenous (IV) infusion for up to six cycles.
7
Total61

Baseline characteristics

CharacteristicDose 2TotalDose 3Dose 4Dose 5Dose 1Dose 6Dose 7Dose 8Dose 9Melanoma Expansion Cohort
Age, Continuous61.1 years
STANDARD_DEVIATION 3.6
66.0 years
STANDARD_DEVIATION 10
81.4 years
STANDARD_DEVIATION 9.6
59.8 years
STANDARD_DEVIATION 13.2
67.2 years
STANDARD_DEVIATION 5
69.4 years
STANDARD_DEVIATION 8.5
67.3 years
STANDARD_DEVIATION 6.4
64.4 years
STANDARD_DEVIATION 7
67.4 years
STANDARD_DEVIATION 8.8
59.0 years
STANDARD_DEVIATION 12.5
71.3 years
STANDARD_DEVIATION 10.5
ECOG Performance Status at Screening
Four
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
ECOG Performance Status at Screening
Not Done
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
ECOG Performance Status at Screening
One
2 Participants42 Participants1 Participants6 Participants5 Participants1 Participants4 Participants1 Participants14 Participants5 Participants3 Participants
ECOG Performance Status at Screening
Three
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
ECOG Performance Status at Screening
Two
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
ECOG Performance Status at Screening
Zero
0 Participants19 Participants1 Participants0 Participants1 Participants1 Participants2 Participants4 Participants3 Participants3 Participants4 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
1 Participants8 Participants0 Participants1 Participants0 Participants2 Participants1 Participants0 Participants2 Participants1 Participants0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
1 Participants52 Participants2 Participants5 Participants5 Participants0 Participants5 Participants5 Participants15 Participants7 Participants7 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants1 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants3 Participants0 Participants1 Participants0 Participants0 Participants1 Participants0 Participants0 Participants1 Participants0 Participants
Race (NIH/OMB)
Black or African American
0 Participants5 Participants0 Participants1 Participants1 Participants0 Participants1 Participants0 Participants1 Participants1 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
1 Participants3 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants2 Participants0 Participants0 Participants
Race (NIH/OMB)
White
1 Participants50 Participants2 Participants4 Participants5 Participants2 Participants4 Participants5 Participants14 Participants6 Participants7 Participants
Sex: Female, Male
Female
0 Participants34 Participants0 Participants4 Participants3 Participants0 Participants5 Participants5 Participants8 Participants5 Participants4 Participants
Sex: Female, Male
Male
2 Participants27 Participants2 Participants2 Participants3 Participants2 Participants1 Participants0 Participants9 Participants3 Participants3 Participants
Type of Cancer Under Study
Breast
0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants
Type of Cancer Under Study
Cervical
0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants
Type of Cancer Under Study
Colorectal
1 Participants15 Participants0 Participants3 Participants4 Participants1 Participants2 Participants1 Participants1 Participants2 Participants0 Participants
Type of Cancer Under Study
Esophagus
0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants
Type of Cancer Under Study
Gastric
0 Participants4 Participants0 Participants2 Participants0 Participants0 Participants0 Participants0 Participants0 Participants2 Participants0 Participants
Type of Cancer Under Study
Head and Neck
0 Participants2 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants1 Participants0 Participants0 Participants
Type of Cancer Under Study
Lung
1 Participants6 Participants0 Participants1 Participants0 Participants0 Participants0 Participants1 Participants2 Participants1 Participants0 Participants
Type of Cancer Under Study
Malignant Cutaneous Melanoma
0 Participants7 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants1 Participants0 Participants5 Participants
Type of Cancer Under Study
Malignant Uveal Melanoma
0 Participants3 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants2 Participants
Type of Cancer Under Study
Mesothelioma
0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants
Type of Cancer Under Study
Other
0 Participants9 Participants0 Participants0 Participants0 Participants1 Participants2 Participants1 Participants4 Participants1 Participants0 Participants
Type of Cancer Under Study
Ovarian
0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants
Type of Cancer Under Study
Pancreatic
0 Participants8 Participants0 Participants0 Participants1 Participants0 Participants1 Participants0 Participants6 Participants0 Participants0 Participants
Type of Cancer Under Study
Prostate
0 Participants2 Participants2 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
EG006
affected / at risk
EG007
affected / at risk
EG008
affected / at risk
EG009
affected / at risk
deaths
Total, all-cause mortality
0 / 20 / 20 / 21 / 61 / 60 / 60 / 50 / 170 / 80 / 7
other
Total, other adverse events
2 / 22 / 21 / 26 / 66 / 66 / 65 / 517 / 177 / 87 / 7
serious
Total, serious adverse events
0 / 20 / 20 / 23 / 63 / 63 / 60 / 58 / 174 / 84 / 7

Outcome results

Primary

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

Population: The PK analyses were performed for all subjects in the PK population (all subjects that received at least one dose plasma KZR-261 concentration measurement during Cycles 1 and 2 of treatment).

ArmMeasureGroupValue (GEOMETRIC_MEAN)Dispersion
Dose 1Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 1, Day 15580.6 ng/mLGeometric Coefficient of Variation 35.5
Dose 1Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 1, Day 1601.5 ng/mLGeometric Coefficient of Variation 26.9
Dose 1Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 2, Day 1566.5 ng/mLGeometric Coefficient of Variation 13.3
Dose 1Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 2, Day 15603.2 ng/mLGeometric Coefficient of Variation 20.7
Dose 2Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 1, Day 152160.0 ng/mL—
Dose 2Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 2, Day 151334.6 ng/mLGeometric Coefficient of Variation 61.3
Dose 2Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 1, Day 11414.9 ng/mLGeometric Coefficient of Variation 1.5
Dose 2Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 2, Day 11724.4 ng/mLGeometric Coefficient of Variation 46.7
Dose 3Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 1, Day 11536.1 ng/mLGeometric Coefficient of Variation 34.7
Dose 3Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 2, Day 152128.8 ng/mLGeometric Coefficient of Variation 36.3
Dose 3Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 1, Day 152413.2 ng/mLGeometric Coefficient of Variation 46
Dose 3Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 2, Day 12406.6 ng/mLGeometric Coefficient of Variation 57.4
Dose 4Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 2, Day 13712.8 ng/mLGeometric Coefficient of Variation 54.5
Dose 4Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 1, Day 154149.8 ng/mLGeometric Coefficient of Variation 45.6
Dose 4Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 1, Day 12793.5 ng/mLGeometric Coefficient of Variation 44.9
Dose 4Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 2, Day 153510.7 ng/mLGeometric Coefficient of Variation 27.5
Dose 5Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 2, Day 154409.6 ng/mLGeometric Coefficient of Variation 28.6
Dose 5Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 1, Day 154409.6 ng/mLGeometric Coefficient of Variation 40.2
Dose 5Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 1, Day 15126.6 ng/mLGeometric Coefficient of Variation 37.8
Dose 5Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 2, Day 14359.1 ng/mLGeometric Coefficient of Variation 18.7
Dose 6Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 1, Day 157571.7 ng/mLGeometric Coefficient of Variation 23.8
Dose 6Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 2, Day 157343.5 ng/mLGeometric Coefficient of Variation 24.9
Dose 6Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 1, Day 17475.8 ng/mLGeometric Coefficient of Variation 10.9
Dose 6Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 2, Day 16686.2 ng/mLGeometric Coefficient of Variation 21.1
Dose 7Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 1, Day 1511906.8 ng/mLGeometric Coefficient of Variation 23.6
Dose 7Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 1, Day 19531.2 ng/mLGeometric Coefficient of Variation 39.5
Dose 7Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 2, Day 114497.6 ng/mLGeometric Coefficient of Variation 42.2
Dose 7Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 2, Day 1512218.5 ng/mLGeometric Coefficient of Variation 11
Dose 8Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 2, Day 1515342.7 ng/mLGeometric Coefficient of Variation 31.4
Dose 8Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 2, Day 112208.5 ng/mLGeometric Coefficient of Variation 36
Dose 8Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 1, Day 1512917.1 ng/mLGeometric Coefficient of Variation 36
Dose 8Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 1, Day 112159.8 ng/mLGeometric Coefficient of Variation 27.8
Dose 9Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 1, Day 1525955.5 ng/mLGeometric Coefficient of Variation 154.2
Dose 9Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 2, Day 1518300.0 ng/mL—
Dose 9Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 1, Day 116346.5 ng/mLGeometric Coefficient of Variation 27.4
Dose 9Maximum Plasma Concentration of KZR-261 (Part 1)Cycle 2, Day 131491.0 ng/mLGeometric Coefficient of Variation 260.2
Primary

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

Population: All participants who received at least 1 dose of study treatment (KZR-261).

ArmMeasureGroupValue (NUMBER)
Dose 1Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Death (Grade 5)0 participants
Dose 1Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Severe (Grade 3)0 participants
Dose 1Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Moderate (Grade 2)0 participants
Dose 1Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Life-threatening (Grade 4)0 participants
Dose 1Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Mild (Grade 1)2 participants
Dose 2Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Death (Grade 5)0 participants
Dose 2Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Life-threatening (Grade 4)0 participants
Dose 2Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Severe (Grade 3)0 participants
Dose 2Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Moderate (Grade 2)0 participants
Dose 2Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Mild (Grade 1)2 participants
Dose 3Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Death (Grade 5)0 participants
Dose 3Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Severe (Grade 3)0 participants
Dose 3Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Mild (Grade 1)0 participants
Dose 3Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Moderate (Grade 2)1 participants
Dose 3Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Life-threatening (Grade 4)0 participants
Dose 4Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Life-threatening (Grade 4)0 participants
Dose 4Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Death (Grade 5)1 participants
Dose 4Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Moderate (Grade 2)2 participants
Dose 4Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Severe (Grade 3)3 participants
Dose 4Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Mild (Grade 1)0 participants
Dose 5Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Death (Grade 5)1 participants
Dose 5Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Mild (Grade 1)0 participants
Dose 5Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Moderate (Grade 2)1 participants
Dose 5Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Severe (Grade 3)4 participants
Dose 5Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Life-threatening (Grade 4)0 participants
Dose 6Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Moderate (Grade 2)0 participants
Dose 6Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Mild (Grade 1)2 participants
Dose 6Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Life-threatening (Grade 4)0 participants
Dose 6Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Death (Grade 5)0 participants
Dose 6Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Severe (Grade 3)4 participants
Dose 7Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Death (Grade 5)0 participants
Dose 7Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Severe (Grade 3)1 participants
Dose 7Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Mild (Grade 1)1 participants
Dose 7Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Moderate (Grade 2)1 participants
Dose 7Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Life-threatening (Grade 4)2 participants
Dose 8Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Severe (Grade 3)5 participants
Dose 8Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Mild (Grade 1)0 participants
Dose 8Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Death (Grade 5)0 participants
Dose 8Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Life-threatening (Grade 4)12 participants
Dose 8Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Moderate (Grade 2)0 participants
Dose 9Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Death (Grade 5)0 participants
Dose 9Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Moderate (Grade 2)0 participants
Dose 9Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Mild (Grade 1)0 participants
Dose 9Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Severe (Grade 3)2 participants
Dose 9Number and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Life-threatening (Grade 4)5 participants
Melanoma Expansion CohortNumber and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Moderate (Grade 2)2 participants
Melanoma Expansion CohortNumber and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Mild (Grade 1)0 participants
Melanoma Expansion CohortNumber and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Life-threatening (Grade 4)5 participants
Melanoma Expansion CohortNumber and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Death (Grade 5)0 participants
Melanoma Expansion CohortNumber and Percentage of Participants Experiencing Adverse Events as Assessed by CTCAE v5.0 (Part 1 & 2)Severe (Grade 3)0 participants
Primary

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

Population: The DLT Evaluable Population consists of all participants who either met the following minimal exposure criteria and have sufficient safety evaluations without having a DLT, or have experienced a DLT during the DLT assessment period. Participants who did not experience a DLT in Dose Escalation must have received all of their scheduled doses (Days 1, 8, and 15) during the DLT assessment period with completed follow-up data available through 28 days of Cycle 1 to be DLT-assessable.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Dose 1Number and Percentage of Participants Experiencing Dose-limiting Toxicities0 Participants
Dose 2Number and Percentage of Participants Experiencing Dose-limiting Toxicities0 Participants
Dose 3Number and Percentage of Participants Experiencing Dose-limiting Toxicities0 Participants
Dose 4Number and Percentage of Participants Experiencing Dose-limiting Toxicities1 Participants
Dose 5Number and Percentage of Participants Experiencing Dose-limiting Toxicities1 Participants
Dose 6Number and Percentage of Participants Experiencing Dose-limiting Toxicities0 Participants
Dose 7Number and Percentage of Participants Experiencing Dose-limiting Toxicities0 Participants
Dose 8Number and Percentage of Participants Experiencing Dose-limiting Toxicities0 Participants
Dose 9Number and Percentage of Participants Experiencing Dose-limiting Toxicities1 Participants
Primary

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

Population: The PK analyses were performed for all subjects in the PK population (all subjects that received at least one dose plasma KZR-261 concentration measurement during Cycles 1 and 2 of treatment).

ArmMeasureGroupValue (GEOMETRIC_MEAN)Dispersion
Dose 1The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 1, Day 15528.6 hr*ng/mLGeometric Coefficient of Variation 20.5
Dose 1The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 2, Day 15568.6 hr*ng/mLGeometric Coefficient of Variation 21.8
Dose 1The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 2, Day 1532.2 hr*ng/mLGeometric Coefficient of Variation 2.9
Dose 1The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 1, Day 1653.2 hr*ng/mLGeometric Coefficient of Variation 14.5
Dose 2The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 1, Day 11483.4 hr*ng/mLGeometric Coefficient of Variation 101.6
Dose 2The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 2, Day 151304.5 hr*ng/mLGeometric Coefficient of Variation 78.3
Dose 2The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 1, Day 152596.4 hr*ng/mL—
Dose 2The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 2, Day 11506.8 hr*ng/mLGeometric Coefficient of Variation 68.2
Dose 3The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 2, Day 12485.0 hr*ng/mLGeometric Coefficient of Variation 12.1
Dose 3The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 1, Day 12252.7 hr*ng/mLGeometric Coefficient of Variation 13.7
Dose 3The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 1, Day 152511.2 hr*ng/mLGeometric Coefficient of Variation 42.4
Dose 3The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 2, Day 152126.4 hr*ng/mLGeometric Coefficient of Variation 22.7
Dose 4The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 1, Day 15592.0 hr*ng/mLGeometric Coefficient of Variation 74.6
Dose 4The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 1, Day 154259.1 hr*ng/mLGeometric Coefficient of Variation 26.4
Dose 4The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 2, Day 16536.5 hr*ng/mLGeometric Coefficient of Variation 80.4
Dose 4The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 2, Day 155135.9 hr*ng/mLGeometric Coefficient of Variation 53.6
Dose 5The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 1, Day 16427.1 hr*ng/mLGeometric Coefficient of Variation 30.8
Dose 5The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 2, Day 156246.6 hr*ng/mLGeometric Coefficient of Variation 28.2
Dose 5The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 2, Day 17030.0 hr*ng/mLGeometric Coefficient of Variation 21.6
Dose 5The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 1, Day 156280.1 hr*ng/mLGeometric Coefficient of Variation 31.8
Dose 6The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 2, Day 110171.0 hr*ng/mLGeometric Coefficient of Variation 18
Dose 6The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 1, Day 158944.0 hr*ng/mLGeometric Coefficient of Variation 16.4
Dose 6The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 1, Day 19919.2 hr*ng/mLGeometric Coefficient of Variation 11.1
Dose 6The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 2, Day 158958.0 hr*ng/mLGeometric Coefficient of Variation 23.2
Dose 7The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 2, Day 1517093.8 hr*ng/mLGeometric Coefficient of Variation 16
Dose 7The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 1, Day 115766.7 hr*ng/mLGeometric Coefficient of Variation 15.3
Dose 7The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 1, Day 1514624.8 hr*ng/mLGeometric Coefficient of Variation 13.9
Dose 7The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 2, Day 120581.5 hr*ng/mLGeometric Coefficient of Variation 36.2
Dose 8The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 2, Day 120847.3 hr*ng/mLGeometric Coefficient of Variation 57.6
Dose 8The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 1, Day 1518088.1 hr*ng/mLGeometric Coefficient of Variation 27
Dose 8The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 1, Day 122918.9 hr*ng/mLGeometric Coefficient of Variation 45.4
Dose 8The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 2, Day 1522390.0 hr*ng/mLGeometric Coefficient of Variation 31.7
Dose 9The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 1, Day 134948.3 hr*ng/mLGeometric Coefficient of Variation 31.7
Dose 9The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 2, Day 148172.7 hr*ng/mLGeometric Coefficient of Variation 92.3
Dose 9The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 1, Day 1538084.6 hr*ng/mLGeometric Coefficient of Variation 96.2
Dose 9The Plasma Concentration Time Curve of KZR-261 (Part 1)Cycle 2, Day 1537991.6 hr*ng/mL—
Secondary

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.

Time frame: 20 months

Population: The Response Evaluable Population is defined as all participants who received at least 1 dose of study treatment (KZR-261) and who have a baseline and at least 1 post-baseline anti-tumor response assessment.

ArmMeasureValue (NUMBER)
Dose 1Objective Response (ORR) Following KZR-2610 participants
Dose 2Objective Response (ORR) Following KZR-2610 participants
Dose 3Objective Response (ORR) Following KZR-2610 participants
Dose 4Objective Response (ORR) Following KZR-2610 participants
Dose 5Objective Response (ORR) Following KZR-2610 participants
Dose 6Objective Response (ORR) Following KZR-2610 participants
Dose 7Objective Response (ORR) Following KZR-2610 participants
Dose 8Objective Response (ORR) Following KZR-2610 participants
Dose 9Objective Response (ORR) Following KZR-2610 participants
Melanoma Expansion CohortObjective Response (ORR) Following KZR-2610 participants
Secondary

Overall Survival of Participants Treated With KZR-261

Time of overall survival for participants treated with KZR-261.

Time frame: 20 months

Population: The Response Evaluable Population is defined as all participants who received at least 1 dose of study treatment (KZR-261) and who have a baseline and at least 1 post-baseline anti-tumor response assessment.

ArmMeasureValue (MEDIAN)
Dose 1Overall Survival of Participants Treated With KZR-26121.7 weeks
Dose 2Overall Survival of Participants Treated With KZR-26122.6 weeks
Dose 3Overall Survival of Participants Treated With KZR-261NA weeks
Dose 4Overall Survival of Participants Treated With KZR-26117.9 weeks
Dose 5Overall Survival of Participants Treated With KZR-261NA weeks
Dose 6Overall Survival of Participants Treated With KZR-261NA weeks
Dose 7Overall Survival of Participants Treated With KZR-26153.4 weeks
Dose 8Overall Survival of Participants Treated With KZR-26112.4 weeks
Dose 9Overall Survival of Participants Treated With KZR-261NA weeks
Melanoma Expansion CohortOverall Survival of Participants Treated With KZR-26124.6 weeks
Secondary

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

Population: The Response Evaluable Population is defined as all participants who received at least 1 dose of study treatment (KZR-261) and who have a baseline and at least 1 post-baseline anti-tumor response assessment.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Dose 1Participants With Clinical Benefit of Stable Disease Following KZR-2610 Participants
Dose 2Participants With Clinical Benefit of Stable Disease Following KZR-2610 Participants
Dose 3Participants With Clinical Benefit of Stable Disease Following KZR-2610 Participants
Dose 4Participants With Clinical Benefit of Stable Disease Following KZR-2610 Participants
Dose 5Participants With Clinical Benefit of Stable Disease Following KZR-2612 Participants
Dose 6Participants With Clinical Benefit of Stable Disease Following KZR-2611 Participants
Dose 7Participants With Clinical Benefit of Stable Disease Following KZR-2611 Participants
Dose 8Participants With Clinical Benefit of Stable Disease Following KZR-2612 Participants
Dose 9Participants With Clinical Benefit of Stable Disease Following KZR-2610 Participants
Melanoma Expansion CohortParticipants With Clinical Benefit of Stable Disease Following KZR-2611 Participants
Secondary

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

Population: The Response Evaluable Population is defined as all subjects who receive at least 1 dose of study treatment (KZR-261) and who have a baseline and at least 1 post-baseline anti-tumor response assessment. For participants who have neither progressed nor died, PFS is censored at the date of the last disease assessment. PFS at 4 months and 6 months are defined as subjects alive and progression-free at 4 months and at 6 months, respectively, after the initiation of study treatment.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Dose 1Progression-free Survival of Participants Treated With KZR-2616 Months0 Participants
Dose 1Progression-free Survival of Participants Treated With KZR-2614 Months0 Participants
Dose 2Progression-free Survival of Participants Treated With KZR-2616 Months0 Participants
Dose 2Progression-free Survival of Participants Treated With KZR-2614 Months0 Participants
Dose 3Progression-free Survival of Participants Treated With KZR-2616 Months0 Participants
Dose 3Progression-free Survival of Participants Treated With KZR-2614 Months0 Participants
Dose 4Progression-free Survival of Participants Treated With KZR-2614 Months0 Participants
Dose 4Progression-free Survival of Participants Treated With KZR-2616 Months0 Participants
Dose 5Progression-free Survival of Participants Treated With KZR-2614 Months2 Participants
Dose 5Progression-free Survival of Participants Treated With KZR-2616 Months2 Participants
Dose 6Progression-free Survival of Participants Treated With KZR-2616 Months0 Participants
Dose 6Progression-free Survival of Participants Treated With KZR-2614 Months1 Participants
Dose 7Progression-free Survival of Participants Treated With KZR-2614 Months1 Participants
Dose 7Progression-free Survival of Participants Treated With KZR-2616 Months1 Participants
Dose 8Progression-free Survival of Participants Treated With KZR-2614 Months2 Participants
Dose 8Progression-free Survival of Participants Treated With KZR-2616 Months0 Participants
Dose 9Progression-free Survival of Participants Treated With KZR-2616 Months0 Participants
Dose 9Progression-free Survival of Participants Treated With KZR-2614 Months0 Participants
Melanoma Expansion CohortProgression-free Survival of Participants Treated With KZR-2614 Months1 Participants
Melanoma Expansion CohortProgression-free Survival of Participants Treated With KZR-2616 Months1 Participants

Source: ClinicalTrials.gov · Data processed: Feb 12, 2026