A Phase 1 Study of KZR-261, a Small Molecule Sec61 Inhibitor, in Subjects With Advanced Solid Malignancies
Phase: PHASE1
Conditions: Advanced/Metastatic Solid Tumor
Sponsor: Kezar Life Sciences, Inc.

KZR-261-101 
A PHASE 1 STUDY OF KZR-261, A SMALL 
MOLECULE SEC61 INHIBITOR, IN 
SUBJECTS WITH ADVANCED SOLID 
MALIGNANCIES 
 
 
Clinicaltrials.gov Identifier 
NCT05047536 
Date of protocol: 
02 October 2023 

 
 
CLINICAL STUDY PROTOCOL 
 
 
Confidentiality Statement 
The concepts and information contained herein are confidential and proprietary and shall not be 
disclosed in whole or part without the express written consent of the Sponsor. 
 
Compliance Statement 
This study will be conducted in accordance with this protocol, the International Council for 
Harmonisation (ICH), Guideline for Good Clinical Practice (GCP), and the 
applicable country and regional (local) regulatory requirements. 
 
 
 
Protocol Title:  
A Phase 1 Study of KZR-261, a Small Molecule Sec61 Inhibitor, in Subjects 
with Advanced Solid Malignancies 
Protocol Number: 
KZR-261-101 
Investigational Product: KZR-261 
Indication:  
Advanced solid malignancies 
Development Phase: 
Phase 1 
 
 
Sponsor: 
Kezar Life Sciences, Inc. 
4000 Shoreline Court, Suite 300 
South San Francisco, CA 94080 
Original Protocol Date: 29 April 2021 
Version / Date: 
Version 1.0 / 29 April 2021 
Version 2.0 / 08 September 2021 
Version 3.0 / 05 December 2022 
Version 4.0 / 27 March 2023 
Version 5.0 / 02 October 2023 
 
 
 
 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
2 
CONFIDENTIAL 
 
PROTOCOL ACCEPTANCE PAGE 
 
Protocol Title: 
A Phase 1 Study of KZR-261, a Small Molecule Sec61 Inhibitor, in 
Subjects with Advanced Solid Malignancies 
Protocol Number: 
KZR-261-101 
Confidentiality and Current Good Clinical Practice (cGCP) Compliance Statement 
I, the undersigned, have reviewed this protocol (and amendments), including appendices. I am 
aware of my responsibilities as an Investigator under the International Council for Harmonisation 
(ICH) Guideline for cGCP, the Declaration of Helsinki, all local, regional, and national 
regulatory requirements (including the Code of Federal Regulations [CFR] Title 21 for United 
States Investigators), requirements of the applicable Institutional Review Board 
(IRB)/Independent Ethics Committee (IEC), and the clinical trial protocol. I agree to conduct the 
trial according to these regulations and guidelines, to appropriately direct and assist the staff 
under my control that will be involved in the trial, and to ensure that all staff members are aware 
of their clinical trial responsibilities. 
Once the protocol has been approved by the IEC/IRB, I will not modify this protocol without 
obtaining prior approval of Kezar Life Sciences and of the IEC/IRB. I will submit the protocol 
amendments and/or any Informed Consent Form (ICF) modifications to Kezar Life Sciences and 
IEC/IRB, and approval will be obtained before any amendments are implemented. 
I understand that all information obtained during the conduct of the study with regard to the 
subjects’ state of health will be regarded as confidential. No subjects’ names will be disclosed. 
All subjects will be identified by assigned numbers on all electronic case report forms (eCRFs), 
laboratory samples, or source documents forwarded to the Sponsor. Clinical information may be 
reviewed by the Sponsor or its agents or regulatory agencies. Agreement must be obtained from 
the subject before disclosure of subject information to a third party. 
Information developed in this clinical study may be disclosed by Kezar Life Sciences, to other 
clinical Investigators, regulatory agencies, or other health authority or government agencies as 
required. 
Investigator’s Name: 
 
Name of Institution/Site: 
 
Signature: 
 
Date: 
 
 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
3 
CONFIDENTIAL 
STUDY PERSONNEL 
Clinical Study Lead: Kezar Life Sciences, Inc. 
Name: 
 
Title: 
 
Address: 
4000 Shoreline Court, Suite 300 
South San Francisco, CA 94080 
United States 
Medical Monitor: 
 
Name: 
 
Title: 
Medical Monitor 
Address: 
 
 
 
Telephone No.: 
 
SAE Reporting Contact 
Safety Lead: 
 
Name: 
 
Title: 
Project Manager 
SAE Reporting Details (to be used for submitting the SAE forms): 
 
Central Safety Fax: 
 
* = country exit code 
 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
 
4 
CONFIDENTIAL 
PROTOCOL SYNOPSIS 
INVESTIGATIONAL PRODUCT (IP) 
Name of IP 
KZR-261 
 
  
Protocol ID 
KZR-261-101 
Protocol Title 
A Phase 1 Study of KZR-261, a Small Molecule Sec61 Inhibitor, in 
Subjects with Advanced Solid Malignancies  
Short Title 
A Phase 1 Study of KZR-261 in Subjects with Advanced Solid 
Malignancies 
Study Phase 
Phase 1 
CLINICAL CONDITION(S)/INDICATION(S) 
Dose Escalation (Part 1) 
• 
Advanced/metastatic solid malignancies (~70 subjects). 
Dose Expansion (Part 2A) 
• 
Tumor-specific cohorts (15 subjects, may increase up to 35 subjects as determined by 
prespecified futility criteria in Stage 1 and if the tumor type is not selected for investigation in 
Part 2B). 
o Malignant melanoma (including uveal melanoma) 
o Malignant mesothelioma 
o Metastatic castration-resistant prostate cancer (mCRPC) 
o Metastatic colorectal carcinoma (mCRC) 
• 
All-Tumors cohort (up to 35 biopsy-evaluable subjects) 
o Other advanced solid malignancies with tumor tissue at baseline (fresh biopsy required) 
Dose Optimization (Part 2B) 
• 
Up to 4 tumor types from Dose Expansion (~30 subjects per tumor type [~15 subjects/dose 
level]). 
Additional (or different) tumor types may be investigated at the Sponsor’s discretion in Part 2 if 
evidence of anti-tumor activity of KZR-261 during Part 1 or in the All-Tumors cohort in Part 2 supports 
further evaluation. 
STUDY DESIGN 
Study Type 
Interventional 
Allocation 
Multicenter, United States 
Blinding/Masking 
Open-label 
Primary Purpose 
Phase 1, first-in-human 
Planned Duration of Subject 
Participation 
Approximately 20 months: 4-week Screening Period, 24-week 
Treatment Period (6 cycles, 4 weeks each), 30-day Safety Follow-Up 
Period, 12-month Long Term Follow-up Period (after last dose of 
study treatment). 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
 
5 
CONFIDENTIAL 
Overview of Study Design 
This first-in-human, open-label, multicenter, Phase 1 study of KZR-261 is 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). KZR-261 will be administered as a 30- to 60-minute 
intravenous (IV) infusion via a central line on Days 1, 8, and 15 of a 4-week (28-day) treatment cycle. 
Eligible subjects will have locally advanced or metastatic solid malignancies and no approved therapies, 
or refused such therapies if available. 
Subjects will receive KZR-261 for up to 6 cycles. Upon completion of Cycle 6, a subject who is deriving 
clinical benefit may continue treatment at the discretion of the Investigator and with agreement of the 
Medical Monitor. Study treatment will be discontinued at any time for unacceptable adverse events 
(AEs), progressive disease, voluntary study withdrawal by the subject, another discontinuation criterion 
is met, or study closure by the Sponsor (Section 8.1.2). Safety assessments will be collected via safety 
laboratory monitoring, as well as changes from baseline in physical examinations, electrocardiogram 
(ECG) findings, vital sign (VS) measurements, and slit lamp and visual acuity exams. AEs will be 
assessed for severity using the National Cancer Institute Common Terminology Criteria for Adverse 
Events (NCI CTCAE) v5.0. Dose-limiting toxicity (DLTs) will be assessed during Part 1 as defined by 
pre-specified AE criteria detailed in Section 3.2.3.  
Anti-tumor activity will be assessed in accordance with the Response Evaluation Criteria in Solid 
Tumors version 1.1 (RECIST v1.1). Subjects with mCRPC will be assessed per the Prostate Cancer 
Working Group 3 (PCWG3) guidelines.  
Efforts will be made to follow subjects for up to 12 months after the last dose of KZR-261 to assess 
disease status and/or survival. 
The study will be conducted in 2 parts: Part 1 (Dose Escalation), and Part 2 (Part 2A – Dose Expansion 
and Part 2B – Dose Optimization). 
Part 1: Dose Escalation 
In Part 1, increasing doses of KZR-261 will be administered in an “i3+3” design to approximately 
70 subjects to evaluate the safety and tolerability, PK, and pharmacodynamics of KZR-261, including 
identifying the maximum tolerated dose (MTD) or maximum administered dose (MAD).  
Dose-escalation decisions for KZR-261 will be guided by the i3+3 design (Zhou and Ji, 2020; Liu et al., 
2020) as described in Section 3.2.1, with the targeted DLT rate 𝑝𝑇=0.3 and the equivalence interval (EI) 
= [0.25, 0.35]. The starting dose is 1.8 mg/m2. During the DLT assessment period (Cycle 1), doses may 
be held up to 7 days for resolution of non-DLT toxicity.  
A minimum of 2 subjects will be enrolled at each dose level of KZR-261. The number of subjects that 
will be enrolled at each dose level varies, with a typical cohort size of 2-4, and with 6 to approximately 
12 subjects dosed at the putative MTD/MAD. 
Intra-subject Dose Escalation 
Intra-subject dose escalation will be permitted after consultation with the Medical Monitor and in the 
following circumstance only: 
• 
Subject must have completed at least two 28-day cycles of treatment (Cycles 1 and 2). 
• 
Subject may have experienced an AE* ≤Grade 3 with resolution to Grade 1 or baseline in the 
setting of a documented tumor response or stable disease over 2 consecutive assessment 
timepoints. For subjects who experienced a Grade 3 AE, the Investigator and Medical Monitor 
should come to an unequivocal consensus that the potential benefit of an increase in dose will 
outweigh the risk of future AEs. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
 
6 
CONFIDENTIAL 
• 
Subject must not have experienced a DLT. 
• 
Subject must not have experienced a dose reduction for purposes of managing AEs and/or 
laboratory abnormalities. 
• 
The higher dose cohort to which the subject would be escalated has been deemed by the Safety 
Review Committee (SRC) to be safe and adequately tolerated. 
*Note: AEs must be assessed as unrelated to study treatment, such as intercurrent illness or concomitant 
medication. AEs that are assessed as related to study treatment would disqualify a patient from dose 
escalation. 
Definition of DLT 
Toxicities will be assessed by the Investigator using NCI CTCAE v5.0. The attribution of an AE to 
KZR-261 is to be assessed by the Investigator. DLTs are defined in Section 3.2.3. 
Definition of MTD and MAD 
The estimated MTD is the dose level associated with approximately 30% of DLT-evaluable subjects 
experiencing a DLT. The target interval for the DLT rate is 25%-35%. Due to the discreteness of the 
dose levels and in the interest of the safety of subjects, the estimated MTD is the highest tested dose 
level with a DLT rate ≤35% in at least 6-12 DLT-evaluable subjects.  
The MAD is declared without an MTD based on the highest dose level evaluated with an observed DLT 
rate <25% (the lower bound of the MTD range) and where sufficient safety and efficacy signals have 
been observed. 
Subject Replacement 
Subjects enrolled in Part 1 (Dose Escalation) who discontinue from study treatment for reasons other 
than a DLT may be replaced. However, any subject discontinued due to a DLT during Part 1 Cycle 1 
(Dose Escalation) will not be replaced.  
Part 2A: Dose Expansion 
The Dose Expansion phase will commence following determination of the MTD/MAD and a review of 
the totality of safety data from Part 1. Part 2A will further characterize the safety profile of KZR-261 at 
the MTD or MAD and evaluate the anti-tumor activity of KZR-261 in subjects who have select 
malignancies. Up to 175 subjects may be enrolled in up to 4 tumor-specific cohorts (such as malignant 
melanoma [including uveal melanoma], mesothelioma, mCRPC, and mCRC) and 1 “All-Tumors” 
cohort. Additional or different tumor-specific cohorts may be investigated at the Sponsor’s discretion. 
Each tumor-specific cohort will enroll 15 subjects during Stage 1, expanding up to 35 subjects (Stage 2) 
as defined by a prespecified futility analysis and if the tumor type is not selected for investigation in 
Part 2B. If futility is not rejected after Stage 1 (ie, prespecified criteria for futility are met), subsequent 
enrollment to that Part 2A cohort will cease. The All-Tumors cohort may enroll up to 35 biopsy-
evaluable subjects.  
  

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
 
7 
CONFIDENTIAL 
Part 2B: Dose Optimization 
Dose optimization in tumor-specific cohorts may be initiated at the Sponsor’s discretion based on the 
totality of data after the MTD/MAD has been determined. The Sponsor may also choose to cease 
enrollment in Part 2A and initiate enrollment of that tumor type in Part 2B. Approximately 30 subjects 
within each tumor-specific cohort will be randomized in a 1:1 ratio to receive KZR-261 at the 
MTD/MAD or a lower clinically active dose of KZR-261. Based on additional safety data from Part 2A, 
the Sponsor may convene an SRC meeting to determine whether a lower dose than the MTD/MAD as 
determined in Part 1 should be evaluated in Part 2B. Part 2B will further characterize the safety profile 
of KZR-261 to support determination of the RP2D and further evaluate the anti-tumor activity of KZR-
261 in subjects with select malignancies. The number of tumor-specific cohorts to be investigated in 
Part 2B will be at the Sponsor’s discretion. 
Safety Review Committee (SRC) 
The KZR-261 SRC will monitor the dose escalation (Part 1) portion of the study. The SRC will be 
convened periodically and evaluate safety data from each dose escalation cohort as well as review the 
totality of the safety data before proceeding to the dose expansion (Part 2A) or dose optimization (Part 
2B) phases. The SRC will continue to periodically monitor the trial through the dose expansion and dose 
optimization portions of the study. The SRC will include the Medical Monitor (or designate), other 
Kezar representative(s), and participating Investigators. The SRC Charter defines the responsibilities of 
the committee for dose escalation and dose expansion/dose optimization. 
Definition of RP2D 
The RP2D is the dose chosen for further study based on assessment of a favorable benefit-risk profile 
across the totality of Phase 1 study results, including both Parts 1 and 2. 
 
Tumor Specimens for Biomarkers 
Tumor-specific Cohorts 
Tumor biopsies (fresh [preferred] or archived) will be requested pre-treatment. For any subject who 
provides a tumor sample pre-treatment, an additional biopsy of accessible tumor tissue will be requested 
at either the end of Cycle 2 or at PD, whichever comes first.  
All-Tumors Cohort 
Pre-treatment tumor biopsies (fresh only) will be required for subjects enrolled in the All-Tumors cohort 
(exceptions to this requirement may be considered after discussion with the Medical Monitor); an 
additional biopsy of accessible tumor tissue will be required at either the end of Cycle 2 or at PD, 
whichever comes first. 
Study Objectives 
Endpoints 
Primary objective for Part 1:  
• 
To evaluate the safety, tolerability, 
and PK of KZR-261 and identify the 
MTD or MAD. 
Safety: DLTs, AEs and SAEs, deaths, dose reductions, 
treatment interruptions and discontinuations due to 
toxicity, clinical laboratory parameters, physical 
examination, ECG, and ocular examination findings, and 
VS measurements. Identification of the MTD or MAD. 
PK parameters: Maximal plasma concentration (Cmax), 
area under the plasma concentration time curve (AUC), 
elimination half-life (t½), clearance (CL), and volume of 
distribution (Vz). 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
 
8 
CONFIDENTIAL 
Primary objective for Parts 2A and 2B: 
• 
To further characterize the safety 
profile of KZR-261 and identify the 
RP2D 
Safety: AEs and SAEs, deaths, dose reductions, treatment 
interruptions and discontinuations due to toxicity, clinical 
laboratory abnormalities, physical examination, ECG, and 
ocular examination findings, and VS measurements. 
Identification of the RP2D. 
Secondary objectives: 
• 
To detect evidence of anti-tumor 
activity of KZR-261. 
• 
To further characterize the PK of 
KZR-261 (Part 2A and 2B only). 
Anti-tumor activity: Objective response rate (ORR) 
defined as the rate of partial responses (PRs) plus 
complete responses (CRs) according to RECIST v1.1, 
duration of response (DOR), progression-free survival 
(PFS), overall survival (OS), and clinical benefit rate 
(CBR). Subjects with mCRPC will be assessed per 
PCWG3 guidelines. 
PK parameters: KZR-261 plasma concentrations. 
Exploratory objectives: 
• 
To evaluate potential 
pharmacodynamic biomarkers in 
peripheral blood based on gene 
expression and proteomic changes. 
• 
To explore and identify potential 
predictive biomarkers in tissue 
(including tumor) samples based on 
gene expression at baseline. 
• 
To evaluate changes in potential 
predictive biomarkers during 
treatment. 
Exploratory endpoints 
• 
Serum biomarker levels including cytokines and 
other circulating proteins. 
• 
Whole blood gene expression changes. 
• 
Protein profiling of peripheral blood mononuclear 
cells (PBMCs).  
• 
Circulating tumor-associated proteins. 
• 
Changes in circulating tumor DNA. 
• 
Baseline gene and/or protein expression in pre- 
and on-treatment (post-Cycle 2) tumor biopsies to 
identify a potential predictive biomarker(s). 
INVESTIGATIONAL PRODUCT(S), DOSE, AND MODE OF ADMINISTRATION 
Active Product 
Dosage form:  
• 
KZR-261 will be supplied in single-use glass vials delivering 
75 mg of KZR-261 and packaged in single vial cartons. Each 
vial is reconstituted with sterile Water for Injection prior to 
administration. 
Dose and dose frequency: 
• 
Escalating doses until MTD or MAD. 
• 
Starting dose: 1.8 mg/m2 infused IV via a central line over 30 to 
60 minutes on Days 1, 8, and 15 every 28 days. An infusion 
pump or syringe pump will be used for all infusions.  
SUBJECT SELECTION 
Targeted Accrual 
Dose Escalation (Part 1): ~70 subjects 
Dose Expansion (Part 2A): up to 175 subjects 
Dose Optimization (Part 2B): up to 120 subjects 
Planned Number of Sites 
Dose Escalation (Part 1): ~8 sites 
Dose Expansion and Dose Optimization (Part 2): ~12 additional sites 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
 
9 
CONFIDENTIAL 
Inclusion Criteria 
1. Age ≥18 years. 
2. Willing and able to sign informed consent before initiation of any study-specific procedures or 
treatment. 
3. Histologic or cytologic evidence of a malignant solid tumor (except primary central nervous system 
[CNS] neoplasms), either metastatic or locally advanced and not amenable to surgical resection or 
other locoregional therapies. 
4. Disease that is resistant to or relapsed following available standard systemic therapy, or for which 
there is no standard systemic therapy, or refused such therapies if available. Documentation of 
the reason must be provided for subjects who have not received a standard therapy likely to result in 
clinical benefit. 
5. Eastern Cooperative Oncology Group Performance Status score of 0 or 1. 
6. Adequate baseline hematologic function: 
a. Absolute neutrophil count (ANC) ≥1.5 × 109/L. Myeloid growth factors must not have been 
administered within 7 days before the first dose of KZR-261. 
b. Hemoglobin ≥8 g/dL and no red blood cell (RBC) transfusions during the 14 days before the first 
dose of KZR-261. 
c. Platelet (PLT) count ≥100 × 109/L and no platelet transfusions during the 14 days before the first 
dose of KZR-261. 
7. Adequate baseline organ function, as demonstrated by the following: 
a. Serum creatinine ≤1.5 × upper limit of normal (ULN) (local institution) or calculated creatinine 
clearance ≥60 mL/min by the Cockcroft-Gault formula. 
b. Serum albumin ≥2.5 g/dL. 
c. Bilirubin ≤1.5 × ULN (local institution). 
d. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (local 
institution). Subjects with hepatic metastases may have ALT and AST ≤5 × ULN. 
8. Serum amylase and lipase values <1.5 × ULN (local institution). 
9. Fasting blood sugar <200 mg/dL. 
10. Fasting triglycerides <300 mg/dL. 
11. International normalized ratio (INR) ≤1.5 or prothrombin time (PT) ≤1.5 × ULN (local institution); 
and either partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) 
≤1.5 × ULN. Exceptions are allowed for patients receiving therapeutic anticoagulation for a history 
of thrombosis. Note: Anticoagulation with warfarin is exclusionary. 
12. Female subjects must have negative serum β-human chorionic gonadotropin (β-hCG) test results 
during Screening and negative serum or urine pregnancy test results, whichever is preferred, at 
Baseline if the subject is a woman of childbearing potential (WOCBP), defined as a woman who has 
not undergone a hysterectomy or bilateral oophorectomy or has not been naturally postmenopausal 
for at least 24 consecutive months. 
13. Subjects who are WOCBP must agree to use highly effective contraceptive methods or abstinence 
for the duration of time on the study and continue to use acceptable contraceptive methods for 
3 months after administration of the last dose of study treatment. Highly effective contraception is 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
 
10 
CONFIDENTIAL 
defined as use of the 2-barrier method (eg, female diaphragm and male condom) or 1 barrier method 
with spermicide, intrauterine device, or hormonal contraceptives (eg, implant or oral). If the subject 
is using a hormonal form of contraception, use must have been stable for at least 4 weeks prior to 
Screening. Abstinence will be acceptable only if it is in line with the preferred and usual lifestyle of 
the subject. Periodic abstinence (eg, calendar, ovulation) and withdrawal are not acceptable methods 
of contraception. 
14. Male subjects with female partners of childbearing potential must be congenitally or surgically 
sterile (vasectomy with confirmation of aspermia) or agree to use 2 effective methods of 
contraception including one barrier method (eg, condom with spermicide) and contraception by the 
female partner for the duration of time on the study and for 3 months after administration of the last 
dose of study treatment. Use of a condom is required by men during intercourse with a male or 
female partner to prevent potential delivery of the drug via seminal fluid during the study until the 
End of Treatment visit. 
15. The subject agrees to, and is capable of, adhering to the study visit schedule and other protocol 
requirements, including follow-up for survival. 
16. Willing and able to comply with the requirements of the protocol. 
17. Disease that is measurable by standard imaging techniques according to RECIST v1.1 (Eisenhauer et 
al., 2009). For subjects with prior radiation therapy, measurable lesions must be outside of any prior 
radiation field(s), unless disease progression has been documented following radiation to the site. 
Additional Inclusion Criteria for Parts 2A and 2B (Dose Expansion and Dose Optimization) 
All subjects considered for enrollment into Part 2 of the study must meet the following criteria in 
addition to the criteria listed above. 
18. Subjects who agree to submit fresh or archived tumor tissue must do so during the Screening period.  
19. For subjects who have cutaneous melanoma  
a. Must have histologic or cytologic evidence of disease that is locally advanced or metastatic 
(American Joint Committee on Cancer [AJCC] Stage 3 or 4).  
b. Must have relapsed or be refractory to treatment with currently approved therapies, including an 
immune checkpoint inhibitor(s), or unable to tolerate approved therapy(ies). 
c. For subjects with a RAF V600 mutation, the subject may have received therapy with a small 
molecule RAF V600 inhibitor with or without a small molecule MEK inhibitor. 
20. For subjects who have uveal melanoma  
a. Must have histologic or cytologic evidence of locally advanced unresectable or metastatic uveal 
melanoma.  
b. Disease must be treatment naive or have progressed (radiologically or clinically) on most recent 
therapy. 
21. For subjects who have malignant mesothelioma of the peritoneum or pleura  
a. Must have histologic or cytologic evidence of malignant mesothelioma that is either metastatic or 
locally advanced and not amenable to surgical resection or treatment with localized therapies. 
b. Must have been previously treated with an acceptable platinum-based regimen (eg, cisplatin or 
carboplatin combined with pemetrexed).  
c. The subject may have received Tumor Treating Fields (TTFields).  

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
 
11 
CONFIDENTIAL 
d. Has previously received treatment with an approved immunotherapy unless the subject is not a 
candidate for immunotherapy.  
22. For subjects who have mCRPC  
a. Must have histologically or cytologically documented, locally advanced unresectable or 
metastatic adenocarcinoma of the prostate. 
b. Must have disease progression despite castration by orchiectomy or ongoing luteinizing 
hormone-releasing hormone (LHRH) analogue. 
c. Must have disease that progressed on or after treatment with androgen inhibitors. 
d. Must have prior treatment with a taxane or not be a candidate for treatment with a taxane. 
e. Must have prior treatment with an inhibitor of poly ADP-ribose polymerase (PARP) if the subject 
has a deleterious germline or somatic BRCA 1/2 mutation or another homologous recombination 
repair gene mutation.  
f. Must have progressive disease as defined by PCWG3 criteria (Scher et al., 2016). Note: Patients 
with biochemical progression (ie. rising PSA levels) only are not eligible. 
g. Must have measurable or evaluable disease. Eligible subjects must have at least 1 measurable 
lesion per RECIST v1.1 and/or evidence of relapse/progression in bone per PCWG3. 
23. For subjects who have mCRC 
a. Must have histologic or cytologic evidence of colorectal carcinoma that is locally advanced and 
unresectable or metastatic. 
b. Must have received or demonstrated intolerance to, appropriate therapy consisting of a 
fluoropyrimidine-based regimen with oxaliplatin and/or irinotecan with or without a therapeutic 
targeting vascular endothelial growth factor (VEGF), and with a monoclonal antibody (mAb) 
targeting epidermal growth factor receptor (EGFR), if their tumor lacks a KRAS mutation.  
c. If the subject has a tumor with a RAF V600 mutation, the subject must have received, or 
demonstrated intolerance to, appropriate therapy targeting RAF V600 with or without a small 
molecule MEK inhibitor plus a mAb targeting EGFR.  
d. If the subject has a tumor that is microsatellite instability high (MSI-H), the subject must have 
received or demonstrated intolerance to therapy targeting PD-1.  
e. Must have received no more than 4 prior lines of therapy for mCRC (adjuvant therapy does not 
count as a line of treatment). 
24. For subjects who have relapsed or refractory solid tumors in the All-Tumors cohort (Part 2A), 
excluding primary CNS malignancies  
a. Must be able to submit fresh tumor tissue during the Screening period. Exceptions to this 
requirement may be considered after discussion with the Medical Monitor. 
b. Appendix C includes a list of prioritized tumor types.  
Exclusion Criteria 
Subjects who meet any of the following criteria at Screening will not be enrolled in the study: 
1. Subjects who have participated in Part 1 dose escalation are not eligible to enroll in Part 2A dose 
expansion or Part 2B dose optimization.  

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
 
12 
CONFIDENTIAL 
2. Persistent clinically significant toxicities (≥Grade 2 per NCI CTCAE version 5.0) from previous 
anticancer therapy (excluding alopecia). 
3. Treatment with any systemic anti-cancer therapy within 14 days or treatment with a biologic within 
28 days before the first dose of KZR-261. 
4. Treatment with an investigational drug within 14 days or treatment with a biologic within 28 days 
before the first dose of KZR-261. 
5. Radiation therapy within 14 days before the first dose of KZR-261. 
6. History of prior radiation to the pancreas. 
7. History of diabetes that is not well-controlled. 
8. History of symptomatic gallstones not treated with cholecystectomy within 5 years of Screening. For 
patients with a history of gallstones treated with cholecystectomy, diagnosis of bile duct stones 
within 3 years of Screening. 
9. Major surgical procedure within 28 days before the first dose of KZR-261. Interventional procedures 
such as percutaneous catheters for drainage of an effusion or central line placement may be 
permitted following consultation with the Medical Monitor, unless the central line placement is for 
study treatment. 
10. A history of familial hypertriglyceridemia. 
11. A personal or family history of acute or chronic pancreatitis from any cause.  
12. A diagnosis of Sjogren’s syndrome. 
13. Heavy alcohol use as defined by the Centers for Disease Control and Prevention: ≥15 alcoholic 
drinks for males or ≥8 alcoholic drinks for females per week. 
14. Additional active malignancy that may confound assessment of the study endpoints. Subjects with 
the following concomitant malignancies are eligible: nonmelanoma skin cancer and carcinoma in 
situ (including transitional cell carcinoma, cervical cancer, anal carcinoma, and melanoma in situ). 
Subjects with a history of other secondary malignancies (ie, active malignancy within 2 years before 
study entry) with a low risk of recurrence may be discussed with the Sponsor for consideration of 
enrollment.  
15. Clinically significant cardiovascular disease including, but not limited to, the following: 
a. Uncontrolled or any New York Heart Association Class III or IV congestive heart failure. 
b. History of myocardial infarction, unstable angina, or stroke within 6 months before study entry. 
16. Hypertension or clinically significant arrhythmias not adequately controlled by medication. 
17. Corrected QT (QTc) interval by Fridericia’s formula (QTcF) on resting ECG at Screening or 
Baseline >470 msec. 
18. History of risk factors for Torsades de pointes (eg, heart failure, hypokalemia, family history of long 
QT syndrome). 
19. Uncontrolled, clinically significant pulmonary disease (eg, chronic obstructive pulmonary disease, 
pulmonary hypertension) that, in the opinion of the Investigator, would put the subject at significant 
risk for pulmonary complications during the study (subject must not require supplemental oxygen). 
20. Active, symptomatic CNS metastases. Any surgery or radiation therapy administered for the 
treatment of CNS metastases must have been completed at least 28 days prior to the date of 
informed consent with a follow-up magnetic resonance imaging (MRI) demonstrating no 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
 
13 
CONFIDENTIAL 
progression of previously active lesions. Patients requiring corticosteroids must be on a stable or 
decreasing dose for 4 or more weeks prior to the first dose of KZR-261.  
21. Primary CNS malignancy. 
22. Condition requiring systemic treatment with either corticosteroids (>20 mg daily prednisone 
equivalents) or other immunosuppressive medications within 14 days before the first dose of KZR-
261. Inhaled or topical steroids and adrenal replacement doses ≤20 mg daily prednisone equivalents 
are permitted. 
23. Uncontrolled intercurrent illness including, but not limited to, medical illness that has the potential 
to prevent the patient from completing the first response assessment at the end of Cycle 2 as well as 
psychiatric illness, or social situations that would limit compliance with study requirements. 
24. Known positive status for human immunodeficiency virus (screening is not required). 
25. History of active or chronic hepatitis B or C. Subjects who are HBsAg negative and hepatitis B core 
antibody positive with no detectable HBV DNA at Screening will be allowed into the study and will 
require regular monitoring for hepatitis B virus DNA. Subjects with a history of hepatitis C should 
have received curative treatment and exhibit absence of detectable HCV RNA at Screening.  
26. Any medical condition that, in the opinion of the Investigator, places the subject at unacceptably 
high risk.  
27. Treatment with warfarin.  
28. Concomitant medications that would need to be taken during the course of the study as defined in 
Section 6.2.2. 
29. Women who are pregnant, lactating, or discontinued lactation less than 12 weeks prior to Screening, 
or who plan to become pregnant or initiate lactation during the study. 
30. Unable to comply with the protocol in the Investigator’s or Sponsor’s opinion. 
STATISTICAL METHODS 
A detailed Statistical Analysis Plan will be prepared by the Sponsor and finalized prior to database lock. 
Sample Size Estimates 
Approximately 70 subjects will be enrolled and treated with KZR-261 in Part 1 (Dose Escalation) in an 
“i3+3” design.  
In Part 2A (Dose Expansion), up to 175 subjects will be enrolled based on interim futility analyses for up 
to 4 tumor-specific expansion cohorts and 1 All-Tumors cohort. The tumor-specific cohorts (n = 15 at 
interim) may be increased up to 35 subjects per cohort to more precisely estimate the anti-tumor activity 
of KZR-261, if there is a sufficient efficacy signal in the interim analyses and if the tumor type is not 
selected for investigation in Part 2B (dose optimization). Note: Outcomes (ie, presence or absence of 
clinical benefit) for subjects enrolled in Part 1 with the same tumor type and who received the same dose 
of KZR-261 as evaluated in the corresponding Part 2A, tumor-specific cohort may be included among 
the initial 15 subjects at the interim analysis. 
The All-Tumors cohort may enroll up to 35 biopsy-evaluable subjects. In Part 2B (Dose Optimization), 
up to 120 subjects (~30 per tumor-specific cohort) may be enrolled. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
 
14 
CONFIDENTIAL 
Planned Statistical Analyses 
Safety 
Summaries and descriptive statistics will be generated for all safety data including DLTs, AEs, Grade 3, 
Grade 4, and Grade 5 AEs, SAEs, AEs resulting in dosing reductions, treatment interruptions, or 
treatment discontinuations, clinical laboratory data, vital signs, ECGs, and results of physical and ocular 
examinations. Deaths that occur after the first dose of study drug and through 30 days after the last dose 
of study drug will be considered “on treatment” deaths and will be summarized. All deaths will be listed. 
Anti-tumor Activity 
ORR is defined as the proportion of subjects achieving a best response of CR or PR according to 
RECIST v1.1. Clinical benefit rate is defined as the proportion of subjects achieving a best response of 
CR/PR or stable disease over a period of ≥2 consecutive response assessment time points. Subjects with 
mCRPC will be assessed for response/clinical benefit per PCWG3 guidelines. DOR is defined as the 
date from first occurrence of PR or CR to the date of documented progressive disease (PD) or death. In 
assessing DOR, a subject alive and without disease progression will be censored at the date of the last 
evaluable disease assessment. Progression-free survival is defined as the date of initiation of study 
treatment to the date of documented PD or death from any cause, whichever occurs first. Landmark 
estimates of progression-free survival rate at various time points (eg, 4 months, 6 months) may also be 
calculated. OS is defined as the date of initiation of study treatment to the date of death from any cause.  
The 2-sided exact CI using the Clopper-Pearson method will be calculated for response/clinical benefit 
rates where applicable. Distributions for PFS, DOR, and OS will be estimated by Kaplan-Meier 
methodology. 
Pharmacokinetics 
Plasma concentrations of KZR-261 will be analyzed using noncompartmental methods. PK parameters 
to be calculated (if adequate data are available for estimation) will include, but are not limited to, 
Cmax, AUC, t½, CL, and Vz. Concentrations and PK parameters of KZR-261 will be summarized for each 
dose level using descriptive statistics. 
Exploratory Assessments 
Assessments of various pharmacodynamic study readouts as a function of dose and time post-
administration will be described and related to anticancer activity, PK, and safety parameters. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
15 
CONFIDENTIAL 
TABLE OF CONTENTS 
PROTOCOL ACCEPTANCE PAGE ..............................................................................................2 
STUDY PERSONNEL ....................................................................................................................3 
PROTOCOL SYNOPSIS ................................................................................................................4 
LIST OF ABBREVIATIONS ........................................................................................................21 
1. 
BACKGROUND INFORMATION ...........................................................................24 
1.1. 
Protein Secretion and Sec61 .......................................................................................24 
1.2. 
KZR-261 Background ................................................................................................24 
1.2.1. 
Bioinformatics Approach to Tumor Selection for the Expansion Cohorts .................25 
1.2.2. 
Clinical Indications .....................................................................................................25 
1.2.3. 
Summary of Nonclinical Study Findings ...................................................................26 
1.2.3.1. 
Toxicology ..................................................................................................................26 
1.2.3.2. 
KZR-261 Absorption, Distribution, Metabolism, and Excretion (ADME) ................27 
1.3. 
Study Rationale ...........................................................................................................28 
2. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................29 
2.1. 
Study Objectives .........................................................................................................29 
2.1.1. 
Primary Objective for Part 1 (Dose Escalation) .........................................................29 
2.1.2. 
Primary Objective for Parts 2A and 2B (Dose Expansion and Dose 
Optimization) ..............................................................................................................29 
2.1.3. 
Secondary Objectives .................................................................................................29 
2.1.4. 
Exploratory Objectives ...............................................................................................29 
2.2. 
Study Endpoints ..........................................................................................................29 
2.2.1. 
Primary Endpoints ......................................................................................................29 
2.2.1.1. 
Safety – Part 1 .............................................................................................................29 
2.2.1.2. 
Safety – Parts 2A and 2B ............................................................................................30 
2.2.1.3. 
Pharmacokinetic .........................................................................................................30 
2.2.2. 
Secondary Endpoints ..................................................................................................30 
2.2.2.1. 
Anti-tumor Activity ....................................................................................................30 
2.2.3. 
Exploratory Endpoints ................................................................................................31 
2.2.3.1. 
Exploratory Biomarker Endpoints ..............................................................................31 
3. 
STUDY DESIGN .......................................................................................................32 
3.1. 
Overview of Study Design ..........................................................................................32 
3.2. 
Part 1: Dose Escalation ...............................................................................................34 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
16 
CONFIDENTIAL 
3.2.1. 
Cohort Dose Escalation ..............................................................................................34 
3.2.1.1. 
Dose Level Escalation for Each Cohort (X+1) ...........................................................35 
3.2.2. 
Intra-subject Dose Escalation .....................................................................................36 
3.2.3. 
Definition of Dose-Limiting Toxicity for Part 1 ........................................................37 
3.2.4. 
Definition of Maximum Tolerated Dose, Maximum Administered Dose, and 
Recommended Phase 2 Dose ......................................................................................38 
3.3. 
Part 2A: Dose Expansion ............................................................................................39 
3.4. 
Part 2B: Dose Optimization ........................................................................................39 
3.5. 
Safety Review Committee (Parts 1, 2A, and 2B) .......................................................40 
3.6. 
Planned Duration of Subject Participation (Parts 1, 2A, and 2B) ..............................40 
3.7. 
Number of Planned Sites ............................................................................................40 
4. 
SUBJECT SELECTION .............................................................................................41 
4.1. 
Number of Planned Subjects ......................................................................................41 
4.1.1. 
Subject Screening .......................................................................................................41 
4.2. 
Inclusion and Exclusion Criteria ................................................................................41 
4.2.1. 
Inclusion Criteria ........................................................................................................41 
4.2.2. 
Additional Inclusion Criteria for Parts 2A and 2B (Dose Expansion and 
Dose Optimization) .....................................................................................................43 
4.2.3. 
Exclusion Criteria .......................................................................................................44 
5. 
STUDY DRUG ...........................................................................................................47 
5.1. 
KZR-261 .....................................................................................................................47 
5.1.1. 
Physical Description of KZR-261 ..............................................................................47 
5.1.2. 
Packaging and Labeling of KZR-261 .........................................................................47 
5.1.3. 
Supply, Dispensing, Storage, and Study Drug Accountability for KZR-261 .............47 
6. 
DOSAGE AND TREATMENT ADMINISTRATION ..............................................49 
6.1. 
Treatment Administration ...........................................................................................49 
6.1.1. 
Monitoring of Dose Administration ...........................................................................49 
6.1.2. 
Criteria for Interrupting Treatment During a Treatment Cycle ..................................49 
6.1.3. 
Criteria for Initiation of a New Cycle .........................................................................50 
6.1.4. 
Dose Modification Guidelines for KZR-261 ..............................................................50 
6.1.4.1. 
Dose Interruptions ......................................................................................................50 
6.1.4.2. 
Dose Modifications for Toxicity ................................................................................50 
6.1.5. 
Missed Doses ..............................................................................................................53 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
17 
CONFIDENTIAL 
6.2. 
Prior and Concomitant Medications ...........................................................................53 
6.2.1. 
Permitted Concomitant Medications ..........................................................................54 
6.2.1.1. 
Concurrent Supportive Care .......................................................................................54 
6.2.1.2. 
Other Concomitant Medications .................................................................................54 
6.2.2. 
Prohibited Concurrent Medications/Therapies ...........................................................54 
7. 
STUDY PROCEDURES ............................................................................................55 
7.1. 
Schedule of Study Procedures ....................................................................................55 
7.2. 
Description of Study Procedures ................................................................................55 
7.2.1. 
Medical History ..........................................................................................................55 
7.2.2. 
Physical Examination .................................................................................................55 
7.2.3. 
Pregnancy Testing and Reproduction Precautions .....................................................55 
7.2.4. 
Electrocardiogram .......................................................................................................56 
7.2.5. 
Vital Sign Measurements and Oxygen Saturation ......................................................56 
7.2.6. 
Ocular Examination ....................................................................................................56 
7.2.7. 
Tumor Specimens for Biomarkers ..............................................................................57 
7.2.8. 
Clinical Laboratory Evaluations .................................................................................57 
7.2.8.1. 
Hematology .................................................................................................................57 
7.2.8.2. 
Serum Chemistry ........................................................................................................58 
7.2.8.3. 
Urinalysis ....................................................................................................................58 
7.2.8.4. 
Coagulation Parameters ..............................................................................................58 
7.2.8.5. 
Hemoglobin A1c (HgbA1c) .......................................................................................59 
7.2.9. 
Tumor Markers ...........................................................................................................59 
7.2.10. 
Response Assessments................................................................................................59 
7.3. 
Pharmacokinetic Measurements .................................................................................60 
7.4. 
Exploratory Assessments ............................................................................................60 
7.4.1. 
Pharmacodynamic and Biomarker Measurements .....................................................60 
7.5. 
Sample Management/Future Research .......................................................................60 
8. 
STUDY DISCONTINUATION .................................................................................62 
8.1. 
Stopping Rules for Safety ...........................................................................................62 
8.1.1. 
Study Stopping Rules .................................................................................................62 
8.1.2. 
Individual Subject Stopping Rules .............................................................................62 
8.2. 
Early Withdrawal of Subjects from Study ..................................................................63 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
18 
CONFIDENTIAL 
8.3. 
End of Treatment and End of Study ...........................................................................64 
8.3.1. 
End of Treatment (or Early Withdrawal) Visit ...........................................................64 
8.3.2. 
End of Study ...............................................................................................................64 
8.4. 
Study Termination ......................................................................................................64 
9. 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS ..................................65 
9.1. 
Adverse Event Reporting ............................................................................................65 
9.1.1. 
Definitions ..................................................................................................................65 
9.1.2. 
Assessment of Severity ...............................................................................................65 
9.1.3. 
Assessment of Causality .............................................................................................66 
9.1.4. 
Action Taken ..............................................................................................................66 
9.1.5. 
Follow-up of Adverse Events .....................................................................................67 
9.1.6. 
Documentation and Reporting of Adverse Events .....................................................67 
9.2. 
Serious Adverse Events ..............................................................................................67 
9.2.1. 
Serious Adverse Events Definition .............................................................................67 
9.2.2. 
Serious Adverse Event Reporting and Documentation Requirements .......................68 
9.3. 
Pregnancy Reporting ..................................................................................................68 
9.4. 
Adverse Events of Special Interest .............................................................................69 
9.5. 
Unexpected Adverse Reactions ..................................................................................69 
9.5.1. 
Unexpected Adverse Reaction Definition ..................................................................69 
10. 
STATISTICAL ANALYSES .....................................................................................70 
10.1. 
Sample Size Estimates ................................................................................................70 
10.1.1. 
Part 1 ...........................................................................................................................70 
10.1.2. 
Part 2A ........................................................................................................................70 
10.1.3. 
Part 2B ........................................................................................................................70 
10.2. 
Analysis Populations ..................................................................................................71 
10.3. 
Demographics, Disposition, and Baseline Characteristics .........................................71 
10.4. 
Methods of Analysis ...................................................................................................71 
10.5. 
Statistical Analyses .....................................................................................................71 
10.5.1. 
Dose Escalation Algorithm .........................................................................................71 
10.5.2. 
Estimation of MTD .....................................................................................................72 
10.5.3. 
Simulations and Operating Characteristics of the i3+3 Design ..................................73 
10.5.4. 
Safety Analysis ...........................................................................................................73 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
19 
CONFIDENTIAL 
10.5.5. 
Anti-tumor Activity ....................................................................................................74 
10.5.6. 
Pharmacokinetics ........................................................................................................74 
10.5.7. 
Exploratory Assessments ............................................................................................75 
10.5.8. 
Handling of Missing Data ...........................................................................................75 
10.6. 
Interim Analyses .........................................................................................................75 
11. 
ETHICAL AND ADMINISTRATIVE CONSIDERATIONS ...................................76 
11.1. 
Compliance Statement ................................................................................................76 
11.2. 
Institutional Review Board or Independent Ethics Committee ..................................76 
11.3. 
Informed Consent and Human Subject Protection .....................................................76 
11.4. 
Direct Access to Source Data, Source Documents, and Study Records .....................77 
11.5. 
Data Collection and Handling ....................................................................................77 
11.6. 
Confidentiality ............................................................................................................77 
11.7. 
Financing and Insurance .............................................................................................77 
11.8. 
Audit and Inspection ...................................................................................................78 
11.9. 
Monitoring ..................................................................................................................78 
11.10. 
Quality Control and Quality Assurance ......................................................................78 
11.11. 
Data Management and Coding ...................................................................................78 
11.12. 
Reporting and Publication, Including Archiving ........................................................78 
12. 
REFERENCES ...........................................................................................................80 
13. 
APPENDICES ............................................................................................................81 
APPENDIX A. SCHEDULE OF EVENTS FOR SCREENING AND CYCLES 1 & 2 ...........82 
APPENDIX B. SCHEDULE OF EVENTS FOR CYCLE 3+ ....................................................86 
APPENDIX C. LIST OF PREFERRED TUMORS FOR THE ALL-TUMORS 
COHORT ....................................................................................................................89 
APPENDIX D. LIST OF SENSITIVE SUBSTRATES OF CYP3A4........................................90 
 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
20 
CONFIDENTIAL 
LIST OF TABLES 
Table 1: 
Decision Table in i3+3 Design for up to 12 Subjects Treated at a Given Dose 
with the Targeted DLT Rate 𝒑𝑻=0.3 and the Equivalence Interval (EI) = 
[0.25, 0.35] ..................................................................................................................35 
Table 2: 
Dose Modifications for Isolated Transaminase Elevations ........................................51 
Table 3: 
Dose Modifications for Thrombocytopenia ................................................................51 
Table 4: 
Dose Modifications for Neutropenia ..........................................................................52 
Table 5: 
Dose Modifications for Pancreatic Toxicity ...............................................................52 
Table 6: 
Dose Modifications for Ocular Toxicity .....................................................................52 
Table 7: 
Dose Modifications for Other Toxicity ......................................................................53 
Table 8: 
Hematology Tests .......................................................................................................58 
Table 9: 
Clinical Chemistry Tests .............................................................................................58 
Table 10: Coagulation Tests .......................................................................................................59 
Table 11: Adverse Event Severity Assessment ..........................................................................66 
Table 12: Anti-tumor Assessments .............................................................................................74 
Table 13: Operating Characteristics of Dose Expansion Phase (Part 2A) ..................................75 
 
LIST OF FIGURES 
Figure 1: 
Study Schematic .........................................................................................................33 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
 
22 
CONFIDENTIAL 
FDA 
Food and Drug Administration 
FIH 
first-in-human 
FOB 
functional observation battery 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
HCC 
hepatocellular carcinoma 
HCO3 
bicarbonate 
hERG 
human ether-à-go-go-related gene 
HNSCC 
head and neck squamous cell carcinoma 
HNSTD 
highest non-severely toxic dose 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
INR 
international normalized ratio 
IP 
investigational product 
IRB 
Institutional Review Board 
IV 
intravenous(ly) 
LFT 
liver function test 
LHRH 
luteinizing hormone-releasing hormone 
mAb 
monoclonal antibody 
MAD 
maximum administered dose 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MCV 
mean corpuscular volume 
mCRC 
metastatic colorectal carcinoma 
mCRPC 
metastatic castration-resistant prostate cancer 
MedDRA 
medical dictionary for regulatory activities 
MRI 
magnetic resonance imaging 
MSI-H 
microsatellite instability high 
MTD 
maximum tolerated dose 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
ORR 
objective response rate 
OS 
overall survival 
PBMC 
peripheral blood mononuclear cell 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
 
23 
CONFIDENTIAL 
PCWG3 
Prostate Cancer Working Group 3 
PD 
progressive disease 
PD-1 
programmed death receptor-1 
PET 
positron emission tomography 
PFS 
progression-free survival 
PFS4 
progression-free survival at 4 months 
PFS6 
progression-free survival at 6 months 
PLT 
platelet 
PK 
pharmacokinetic 
PO4 
phosphate 
PR 
partial response 
PSA 
prostate-specific antigen 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
QTc 
corrected QT 
QTcF 
corrected QT by Fridericia’s formula 
RBC 
red blood cell 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RP2D 
recommended Phase 2 dose 
SAE 
serious adverse event 
SRC 
Safety Review Committee 
STD10 
severely toxic dose to 10% of animals 
SUSAR 
suspected unexpected serious adverse reaction 
t½ 
half-life 
TCGA 
The Cancer Genome Atlas 
TTFields 
Tumor Treating Fields 
ULN 
upper limit of normal 
Vz 
volume of distribution 
VEGF 
vascular endothelial growth factor 
VEGFR2 
vascular endothelial growth factor receptor-2 
VS 
vital signs 
WBC 
white blood cell 
WOCBP 
women of childbearing potential 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
24 
CONFIDENTIAL 
1. 
BACKGROUND INFORMATION 
1.1. 
Protein Secretion and Sec61 
Proteins destined for extracellular secretion or cell membrane display require additional 
processing and targeting. For nearly all such proteins (~30% of all expressed genes (Uhlén et al., 
2015), this requires translocation from the cytosol to the endoplasmic reticulum (ER) in a 
process termed co-translational translocation (Dudek et al., 2015). 
Co-translational translocation initiates with translation of short, ribosomal-emergent peptide 
signal sequences unique to each secreted/transmembrane protein. Recruitment machinery 
generically recognizes signal sequences, stalls translation, then localizes the ribosomal-nascent 
protein complex to the translocon, a collection of proteins at the surface of the ER that mediates 
translocation of the translating protein. The core component of the translocon and key arbiter of 
co-translational translocation is an evolutionarily conserved heterotrimeric protein channel 
embedded in the ER membrane known as Sec61. Transmembrane helices of the central Sec61α 
subunit form a clam shell-like channel affording lateral and axial entrance to the ER which 
enables translocation of translating proteins to the ER bilipid membrane and lumen, respectively 
(Lang et al., 2017; Voorhees and Hegde, 2016). Recognition and opening of the lateral gate by 
signal sequences afford entrance of translocating transmembrane proteins toward the ER 
membrane lipid bilayer. Lateral gate opening also widens the pore ring and destabilizes an ER 
lumen-side plug thus allowing axial entrance of translating proteins into the lumen of the ER. 
Protein secretion is especially important in cancer cells that depend on secreted proteins, such as 
growth factors that confer proliferative advantages by influencing the growth, survival, 
metastasis, and cell surface proteins that mediate immunosuppression. Considering the 
fundamental role Sec61 plays as a channel-like protein complex in the membrane of the ER 
through which nearly all secreted and transmembrane proteins must pass during protein 
secretion, Sec61 represents a novel therapeutic target for an anticancer therapy.  
1.2. 
KZR-261 Background 
KZR-261 is a first-in-class small molecule targeting the protein secretion pathway by affecting 
the function of Sec61. Effective targeting of the protein secretion pathway is relevant to multiple 
cancer indications including solid and hematologic malignancies.  
By targeting Sec61, KZR-261 inhibits the secretion of many types of secreted and 
transmembrane proteins that are involved in tumorigenesis and tumor growth. These include 
oncogenic receptor tyrosine kinases (eg, epidermal growth factor receptor [EGFR]), growth 
factors, vascularization (eg, vascular endothelial growth factor [VEGF] and VEGF receptor-2 
[VEGFR2]), and tumor-induced immune suppression (eg, programmed death receptor-1 [PD-1]). 
In nonclinical studies, inhibition of Sec61 resulted in broad anti-tumor activity in a wide range of 
solid and hematologic malignancies, and induced cellular stress, causing cell death via apoptosis. 
KZR-261 and other members of its chemical class produce relevant anticancer activity in a wide 
range of xenografts and syngeneic models of both solid and hematologic malignancies. 
Furthermore, KZR-261 was determined to be well tolerated at doses in repeat-dose toxicity 
studies in rats and monkeys considered relevant for clinical evaluation.  

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
25 
CONFIDENTIAL 
1.2.1. 
Bioinformatics Approach to Tumor Selection for the Expansion Cohorts 
Tumors selected for inclusion in the expansion cohorts were chosen based in part on 
bioinformatic analysis of cancer cell line profiling and publicly available gene expression 
databases. Cancer cell lines were tested in vitro for sensitivity to Sec61 inhibition, revealing 
broad activity against a wide range of malignancies. The correlation between sensitivity to 
treatment and gene expression levels of these cell lines was evaluated by gene set enrichment 
analysis using transcriptomic data from the Cancer Cell Line Encyclopedia (CCLE). 
This analysis identified 7 groups of genes related to processes such as metabolism, transcription, 
translation, protein secretion, and ER stress which are predicted to correlate with sensitivity to 
KZR-261. Expression levels of the 7 gene sets were then profiled in the primary tissue sample 
gene expression database of The Cancer Genome Atlas (TCGA) to identify primary tumor types 
predicted to be sensitive to KZR-261 relative to other tumors or normal tissues. These methods 
identified melanoma, uveal melanoma, mesothelioma, prostate cancer, colorectal cancer, 
urothelial carcinoma, soft tissue sarcoma, head and neck squamous cell carcinoma (HNSCC), 
and hepatocellular carcinoma (HCC), among others, as indications with gene expression patterns 
matching those predicted to be sensitive to KZR-261.  
1.2.2. 
Clinical Indications 
This first-in-human (FIH) study is designed to assess the safety and tolerability of KZR-261 in 
subjects with advanced solid malignancies (locally advanced or metastatic solid malignancies) 
and no approved therapies, or refused such therapies if available. 
The tumors identified for the expansion part of the study were identified by a combination of 
nonclinical data, a bioinformatics analysis (Section 1.2.1), and assessment of clinical unmet 
need. The treatment for cutaneous melanoma has changed dramatically in the last decade with 
the approval of checkpoint inhibitors (eg, anti-PD-1 monoclonal antibodies) and targeted therapy 
to BRAF mutations. However, although the response rate to the newer therapies is high, 
resistance is acquired within 3 years in approximately 40% of patients. Contributing to the unmet 
need is the rising incidence of melanoma in the US (SEER, 2021). Uveal melanoma is a rare 
subset which has limited treatment options. Similarly, despite advances in screening, colorectal 
cancers are rising in incidence especially among young people. Colorectal cancer is the fourth 
most common diagnosed cancer in the US, and the second leading cancer-related cause of death 
(SEER, 2021). Outcomes for metastatic castrate-resistant prostate cancer (mCRPC) have 
improved with next-generation androgen inhibitors such as abiraterone and enzalutamide. 
Although there is clinical impact in the metastatic setting, many patients are receiving these 
agents early in the disease course. Therefore, options for mCRPC in patients who have received 
androgen inhibitors only include taxanes (docetaxel and carbezitaxel), radium 223, and 
sipuleucil-T for general treatment (NCCN, 2021). Metastatic mesothelioma has a <10% 5-year 
survival rate (ACS, 2020) due to lack of beneficial systemic therapies. In addition to the diseases 
that will be targeted for enrollment in the expansion phase, subjects with other tumor types will 
be eligible to enroll in the dose escalation phase and into the All-Tumors cohort of the expansion 
phase. Other tumor types which are of interest based on the bioinformatics approach are 
urothelial carcinoma, soft tissue sarcoma, HNSCC, and HCC. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
26 
CONFIDENTIAL 
1.2.3. 
Summary of Nonclinical Study Findings 
1.2.3.1. 
Toxicology 
Good Laboratory Practice (GLP)-compliant repeat-dose toxicity studies were conducted in rats 
and monkeys. After 4 weeks of weekly intravenous (IV) bolus administration, the severely toxic 
dose to 10% of the animals (STD10) was determined to be 3 mg/kg (18 mg/m2) in rats and the 
highest non-severely toxic dose (HNSTD) was determined to be 1.25 mg/kg (15 mg/m2) in 
monkeys.  
In rats, KZR-261-related gross and organ weight findings and correlative effects were found in 
several secretory organs, including the glandular parenchyma of reproductive (prostate and 
seminal vesicle), respiratory (trachea), special sense (exorbital lacrimal gland), and 
gastrointestinal (stomach, exocrine pancreas, and submandibular and sublingual salivary gland) 
organs. In monkeys, KZR-261-related effects were found in the pancreas (acinar atrophy and 
islet vacuolation), salivary gland (secretory depletion), and the eye (lens degeneration correlating 
to cataracts on ophthalmologic examination). 
In both rats and monkeys, changes in histopathology of the pancreas were partially reversible 
following a 2-week recovery period. Histologic changes in rats correlated with alterations in 
amylase levels but hyperglycemia was not observed at any dose level in the rats. Pancreas 
histology changes in monkeys correlated with increased amylase levels, hyperglycemia, glucose 
and ketones in the urine, and increased triglycerides. 
Cataracts were noted following repeat dosing in monkeys. Bilateral, diffuse anterior and 
posterior cortical cataracts (opacity) were observed in 9/28 animals at ≥2.5 mg/kg (30 mg/m2) on 
Day 19/20 prior to the last dose. The incidence and severity of the cataracts progressed following 
a 2-week recovery period. The presence of cataracts correlated with increased serum and urine 
glucose; however, there was no correlation in total exposure in the animals and no difference in 
the frequency of cataracts between the mid and high dose. No ocular findings were observed in 
the rat study. 
Reproductive system macroscopic and microscopic findings were noted in male and female rats. 
Adverse histologic findings in the prostate gland and seminal vesicles of males were not fully 
reversible. The prostate and seminal vesicular changes in male rats at ≥3.0 mg/kg would be 
expected to alter sperm number and vitality. No histological findings in the prostate or seminal 
vesicles were observed in monkeys at doses up to 5 mg/kg (60 mg/m2). In female rats, mild to 
marked atrophy of the uterus, cervix, and vagina were considered secondary to stress and 
decreases in body weight and were not fully reversible. No histological findings in female 
reproductive organs were noted in monkeys at doses up to 5 mg/kg (60 mg/m2). 
Pancreas, salivary gland, reproductive organs (prostate, seminal vesicles, ovary, and uterus), 
stomach, lungs, bone marrow, and eye (lens) are all secretory organs with high Sec61 expression 
(Uhlén et al., 2015). In addition to the findings described above, lymphodepletion and/or 
decreased cellularity of the thymus and bone marrow and indications of altered liver function 
(increased liver enzymes and decreased albumin and globulin) were noted in both rats and 
monkeys at or above the STD10/HNSTD. 
KZR-261 was found to have no inhibitory effect on the human ether-à-go-go-related gene 
(hERG) with an IC50 ˃1 µM. When assessed for off-target profiling in a panel of 111 receptors 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
27 
CONFIDENTIAL 
and enzymes, KZR-261 showed >50% inhibition of the sodium channel at 10 µM. Sodium 
channel antagonists may be antiepileptic and antiarrhythmic as well as proarrhythmic; agonists 
may also cause cardiac arrhythmia. No signs of cardiovascular effects were observed in any of 
the GLP monkey studies. In monkeys, there were no changes in electrocardiogram (ECG) 
morphology, QT, PR, and QRS intervals, or QTc, to KZR-261 at doses up to 5 mg/kg 
(60 mg/m2). In the repeat-dose rat study, IV doses of 5/4 mg/kg (non-tolerated) were associated 
with several changes in functional observation battery (FOB) in females, which consisted of 
hunched body and lower grip strength of hind and forelimbs in the 5/4 mg/kg females; lower 
body temperature and weights were noted in both the 3 mg/kg and 5/4 mg/kg females. All FOBs 
recovered following a 2-week recovery period. The effects noted in FOB assessments most likely 
reflect the general toxicity of KZR-261. There were no KZR-261-related effects on respiratory or 
neurological assessments in monkeys at doses up to 5 mg/kg (60 mg/m2). 
KZR-261 was not genotoxic when tested in the in vitro mutagenicity (Ames) test, in vitro 
chromosomal aberration assay, and in vivo micronucleus assay in rats. 
To further understand the effect of KZR-261 on fasting glucose levels, non-GLP repeat-dose 
studies were conducted in monkeys in which the rate and schedule of administration was varied. 
Increased hyperglycemia did not appear to correlate with increased exposure but did correlate 
with decreased food-induced insulin secretion. Administration of KZR-261 as a 30-minute 
IV infusion rather than an IV bolus reduced elevations in glucose, triglycerides, lipase, 
pancreatic elastase 1, and amylase levels. Hyperglycemia observed with weekly dosing was also 
attenuated when the same dose was administered biweekly (Q2W). These findings suggest that 
pancreatic toxicity can potentially be attenuated by delivering KZR-261 via a 30-minute 
infusion, thus lowering the maximum plasma concentration (Cmax), or by decreasing the 
frequency of the dose administration. 
In summary, KZR-261 showed minimal off-target activity, no inhibition of hERG, and did not 
induce cardiovascular or respiratory toxicity in vivo. The starting dose for this Phase 1 human 
study is 1.8 mg/m2 (1/10th of the STD10 in rats, the most sensitive species) infused over 
30 minutes. 
1.2.3.2. 
KZR-261 Absorption, Distribution, Metabolism, and Excretion (ADME) 
After single IV bolus and infusion administration of KZR-261 to mice, rats, and monkeys, 
KZR-261 was slowly cleared with clearance values less than hepatic blood flow in all species. 
Terminal half-life (t½) values were 5–17 hours, and drug was still measurable at 24 or 36 hours 
after dosing in all species. Exposure to KZR-261 increased dose proportionally in rats and 
monkeys across the dose ranges tested. No accumulation was observed upon multiple 
administrations of KZR-261 in rats. However, modest accumulation and higher inter-animal 
variability was observed in monkeys at doses above the HNSTD. After an IV bolus or 30-minute 
infusion to mice or rats, KZR-261 was widely distributed to tissues except brain. 
Metabolic profiling using hepatocyte suspensions from rats, monkeys, and humans reveal that a 
single N-demethylation metabolite was the major metabolic pathway. Levels of this metabolite 
were determined to be <5% of parent in rat and monkey plasma, indicating minimal exposure. 
KZR-261 strongly bound to plasma proteins with an overall bound fraction of approximately 
99.984%, 99.986%, 99.998%, and 99.996%, in mouse, rat, dog, and human, respectively. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
28 
CONFIDENTIAL 
KZR-261 showed time-dependent inhibitory effects on cytochrome P450 (CYP) 3A4, and its 
inhibition was quasi-irreversible. Exposures to KZR-261 at concentrations up to 10 µM did not 
induce CYP1A2 or CYP2B6 and resulted in minimal induction of CYP3A4. CYP3A4 plays a 
minor role in the clearance of KZR-261. 
KZR-261 had poor permeability in Caco-2 cells, was not an inhibitor of P-gp, BCRP, OATP1B1, 
OAT1, OCT2, OAT3, and MATE2K, and was a weak inhibitor of OCT1 and MATE1. KZR-261 
showed no substrate potential for OATP1B1, OAT1, OCT1, OAT3, MATE1, and MATE2K. 
1.3. 
Study Rationale 
The heterotrimeric, ER membrane protein complex Sec61 offers an untapped potential 
therapeutic target for a broad spectrum of malignancies. KZR-261 is a novel inhibitor of Sec61 
that potently blocks expression of secreted and membrane proteins and has shown potent anti-
tumor effect in nonclinical models. The nonclinical toxicology profile of KZR-261 is consistent 
with other potent antineoplastic agents. 
Part 1 of this FIH study of KZR-261 is designed to assess the safety, tolerability, and 
pharmacokinetics (PK) of KZR-261 in a standard i3+3 dose escalation design and to inform the 
dose and schedule of KZR-261 for additional investigation in Part 2A (Dose Expansion), Part 2B 
(Dose Optimization), and subsequent Phase 2 studies. The study also seeks to detect preliminary 
anticancer activity in subjects with solid malignancies with an expansion in select malignancies 
such as malignant melanoma (including uveal melanoma), mesothelioma, mCRPC, and 
metastatic colorectal carcinoma (mCRC). The study will also explore protein changes 
(eg, specific Sec61 cargo proteins) in peripheral blood and/or tumor biopsy samples and their 
relationship to KZR-261 treatment and genomic (eg, mutations and translocations) and 
transcriptomic (gene expression) markers in tumors at baseline as predictors of tumor response. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
29 
CONFIDENTIAL 
2. 
STUDY OBJECTIVES AND ENDPOINTS 
2.1. 
Study Objectives 
2.1.1. 
Primary Objective for Part 1 (Dose Escalation) 
• To evaluate the safety, tolerability, and PK of KZR-261 and identify the maximum 
tolerated dose (MTD) or maximum administered dose (MAD). 
2.1.2. 
Primary Objective for Parts 2A and 2B (Dose Expansion and Dose 
Optimization) 
• To further characterize the safety profile of KZR-261 and identify the recommended 
Phase 2 dose (RP2D). 
2.1.3. 
Secondary Objectives 
• To detect evidence of anti-tumor activity of KZR-261. 
• To further characterize the PK of KZR-261 (Part 2A and 2B only). 
2.1.4. 
Exploratory Objectives 
• To evaluate potential pharmacodynamic biomarkers in peripheral blood based on 
gene expression and proteomic changes. 
• To explore and identify potential predictive biomarkers in tissue (including tumor) 
samples based on gene expression at baseline. 
• To evaluate changes in potential predictive biomarkers during treatment. 
2.2. 
Study Endpoints 
2.2.1. 
Primary Endpoints 
2.2.1.1. 
Safety – Part 1 
Safety endpoints include the following: 
• Incidence of dose-limiting toxicities (DLTs) during the DLT assessment period. 
DLTs will be assessed during Part 1 using pre-specified AE criteria detailed in 
Section 3.2.3. 
• Type, incidence, and severity of adverse events (AEs) and serious adverse events 
(SAEs), deaths, dose reductions, treatment interruptions and discontinuations due to 
toxicity, and changes from baseline in clinical laboratory parameters. Adverse events 
will be graded for severity per the National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI CTCAE) version 5.0. 
• Changes from baseline in physical examination, ECG, and ocular examination 
findings. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
30 
CONFIDENTIAL 
• Changes from baseline in vital sign (VS) measurements and pulse oximetry. 
• Identification of the MTD or MAD. 
2.2.1.2. 
Safety – Parts 2A and 2B 
Safety endpoints include the following: 
• Type, incidence, and severity of AEs and SAEs, deaths, dose reductions, treatment 
interruptions and discontinuations due to toxicity, and changes from baseline in 
clinical laboratory parameters. 
• Changes from baseline in physical examination, ECG, and ocular examination 
findings. 
• Changes from baseline in VS measurements and pulse oximetry. 
• Identification of the RP2D. 
2.2.1.3. 
Pharmacokinetic 
PK endpoints (if applicable) include the following: 
• Plasma concentrations, including maximal plasma concentration (Cmax). 
• Area under the plasma concentration-time curve (AUC). 
• Elimination half-life (t½). 
• Clearance (CL). 
• Volume of distribution (Vz). 
2.2.2. 
Secondary Endpoints 
2.2.2.1. 
Anti-tumor Activity 
The anti-tumor activity of KZR-261 will be measured by the following: 
• Objective response rate (ORR) defined as the rate of partial responses (PRs) plus 
complete responses (CRs) according to the revised Response Evaluation Criteria in 
Solid Tumors version 1.1 (RECIST v1.1) guidelines (Eisenhauer et al., 2009). 
Subjects with mCRPC will be assessed per Prostate Cancer Working Group 3 
(PCWG3) guidelines (Scher et al., 2016).  
• Clinical benefit rate (CBR), defined as the proportion of subjects achieving a best 
response of CR/PR or SD over at least 2 consecutive response assessment time points.  
• Duration of response (DOR). 
• Progression-free survival (PFS). 
• Overall survival (OS). 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
31 
CONFIDENTIAL 
2.2.3. 
Exploratory Endpoints 
2.2.3.1. 
Exploratory Biomarker Endpoints 
Exploratory endpoints include the following:  
• Serum biomarker levels including cytokines and other circulating proteins. 
• Whole blood gene expression changes. 
• Protein profiling of peripheral blood mononuclear cells (PBMCs). 
• Circulating tumor-associated proteins. 
• Changes in circulating tumor DNA. 
• Baseline gene and/or protein expression in pre- and on-treatment (post-Cycle 2) 
tumor biopsies to identify a potential predictive biomarker(s). 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
32 
CONFIDENTIAL 
3. 
STUDY DESIGN 
3.1. 
Overview of Study Design 
This FIH, open-label, multicenter, Phase 1 study is designed to assess the safety and tolerability, 
preliminary anti-tumor activity, and the PK characteristics of KZR-261, as well as identify the 
RP2D. KZR-261 will be administered as a 30- to 60-minute IV infusion via a central line on 
Days 1, 8, and 15 of a 4-week (28-day) treatment cycle. (Doses may be held up to 7 days for 
resolution of non-DLT toxicity.) Eligible subjects will have locally advanced or metastatic solid 
malignancies and no approved therapies, or refused such therapies if available. 
The study will be conducted in 2 parts: Part 1 (Dose Escalation) and Part 2 (Part 2A –Dose 
Expansion and Part 2B – Dose Optimization).  
In Part 1, increasing doses of KZR-261 will be administered in an “i3+3” design to 
approximately 70 subjects to evaluate the safety and tolerability, PK, and pharmacodynamics of 
KZR-261, including identifying the MTD or MAD.  
The Dose Expansion phase will commence following determination of the MTD/MAD and a 
review of the totality of safety data from Part 1. Part 2A will further characterize the safety 
profile of KZR-261 at the MTD or MAD and evaluate the anti-tumor activity of KZR-261 in 
subjects who have select malignancies. Up to 175 subjects may be enrolled in up to 4 tumor-
specific cohorts (such as malignant melanoma [including uveal melanoma], mesothelioma, 
mCRPC, and mCRC) and 1 “All-Tumors” cohort. Additional or different tumor-specific cohorts 
may be investigated at the Sponsor’s discretion. Each tumor-specific cohort will enroll 
15 subjects during Stage 1, expanding up to 35 subjects (Stage 2) as defined by a prespecified 
futility analysis and if the tumor type is not selected for investigation in Part 2B (see below). 
If futility is not rejected after Stage 1 (ie, prespecified criteria for futility are met), subsequent 
enrollment to that Part 2A cohort will cease. The All-Tumors cohort may enroll up to 
35 biopsy-evaluable subjects. 
Dose optimization in tumor-specific cohorts may be initiated at the Sponsor’s discretion based 
on the totality of data after the MTD/MAD has been determined. The Sponsor may choose to 
cease enrollment in Part 2A and initiate enrollment of that tumor type in Part 2B. Approximately 
30 subjects within each tumor-specific cohort will be randomized in a 1:1 ratio to receive 
KZR-261 at the MTD/MAD or a lower clinically active dose of KZR-261 in Part 2B. Based on 
additional safety data from Part 2A, the Sponsor may convene an SRC meeting to determine 
whether a lower dose than the MTD/MAD as determined in Part 1 should be evaluated in 
Part 2B. Part 2B will further characterize the safety profile of KZR-261 to support determination 
of the RP2D and further evaluate the anti-tumor activity of KZR-261 in subjects with select 
malignancies. The number of tumor-specific cohorts to be investigated in Part 2B will be at the 
Sponsor’s discretion. 
A schematic representation of the study design is presented in Figure 1.  

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
 
33 
CONFIDENTIAL 
Figure 1: 
Study Schematic 
 
MAD=maximum administered dose; MTD=maximum tolerated dose; RP2D=recommended Phase 2 dose 
*Backfilling of a cohort may occur during dose escalation. 
**Based on additional safety data from Part 2A, the Sponsor may convene an SRC meeting to determine whether a 
lower dose than the MTD/MAD as determined in Part 1 should be evaluated in Part 2B. 
For each subject, written informed consent must be obtained prior to initiating any study 
procedure, including screening assessments for study eligibility (Section 4.2), unless the 
procedure or assessment is consistent with the standard of care for the underlying malignancy. 
Screening assessments must be completed within 28 days prior to the first dose of study 
treatment. Subjects who meet all eligibility criteria will be enrolled in the study and receive their 
first dose of study treatment on Cycle 1 Day 1.  
During the Treatment Period, study assessments will be performed as detailed in the Schedule of 
Events (Appendix A and Appendix B). All study visits will be conducted on an outpatient basis. 
Subjects will receive KZR-261 for up to 6 cycles. Upon completion of Cycle 6, a subject who is 
deriving clinical benefit may continue treatment at the discretion of the Investigator and with 
agreement of the Medical Monitor. Study treatment will be discontinued at any time for 
unacceptable AEs, progressive disease, voluntary withdrawal by the subject, another 
discontinuation criterion is met, or study closure by the Sponsor (Section 8.1.2).  
Following discontinuation of study treatment, subjects will complete an End of Treatment (EOT) 
visit as soon as possible after their last dose of study treatment (Section 8.3). Safety follow-up 
will be conducted by telephone 30 days after the subject’s last dose of study treatment 
(Section 9.1.5). If AEs have not resolved at that time, additional safety follow ups will occur 
approximately every 30 days until resolution of AEs or until, in the opinion of the Investigator, 
the event is stabilized or determined to be chronic. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
   
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
  
 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
34 
CONFIDENTIAL 
Subjects who discontinue study treatment for reasons other than progressive disease (PD) will be 
contacted by telephone approximately every 90 days for 12 months after last study treatment for 
evidence of PD, collection of information about subsequent anti-tumor therapy, and assessment 
of survival status. Subjects who discontinue study treatment for PD will be contacted by 
telephone approximately every 90 days for 12 months after last study treatment for assessment of 
survival status. 
Safety will be assessed as described in Section 2.2.1.1.  
Anti-tumor activity will be assessed as described in Section 2.2.2.1, with assessments of 
response conducted after every 2 treatment cycles.  
3.2. 
Part 1: Dose Escalation 
3.2.1. 
Cohort Dose Escalation 
Dose-escalation decisions for KZR-261 will be guided by the i3+3 design (Zhou and Ji, 2020; 
Liu et al., 2020) with the targeted DLT rate 𝑝𝑇=0.3 and the equivalence interval (EI) = [0.25, 
0.35]. The number of subjects that will be enrolled at each dose level varies, with a minimum of 
2 subjects, a typical cohort size of 2-4, and 6 to approximately 12 subjects dosed at the putative 
MTD or MAD. Table 1, generated using 
, lists the decisions for up to 12 subjects 
treated at a given dose.  
The columns in Table 1 represent the number of subjects enrolled at a given dose, and the row 
represents the number of DLTs at the same dose. The dose-escalation decisions are as follows: 
E: Escalate to the next higher dose; S: Stay at the current dose; D: De-escalate to a lower dose; 
DU: De-escalate to a lower dose, the current dose may not be used again pending advice of the 
Safety Review Committee (SRC). The determination of the dose escalation or dose de-escalation 
will be based on the algorithm as described in Table 1. Safety data from all subjects enrolled in 
each cohort will be reviewed to confirm occurrence of any DLTs experienced during the first 
cycle (DLT assessment period) to determine whether to expand the current cohort or to initiate 
enrollment into the next cohort. Note that if 2 out of 2 subjects have DLTs when treated at the 
lowest dose level the Sponsor, based on recommendations from the SRC, may choose to enroll 
one more subject, amend the study to allow a revised dose regimen (ie, enroll subjects at a lower 
dose or modify the dosing schedule), or terminate the study. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
36 
CONFIDENTIAL 
• no subject exhibited fasting blood sugar (FBS) >200 mg/dL on 2 consecutive 
measures over a 72-hour period after dosing; or 
• no subject exhibited FBS >160 mg/dL three or more times over a 72-hour period after 
dosing. 
Up to a 50% dose increment may occur if:  
• no subject in the most recent cohort required dose reduction for purposes of managing 
AEs and/or laboratory abnormalities;  
• there is resolution of any ≥ Grade 3 AE to Grade 1 or baseline in ≤10 days 
Up to a 33% dose increment may occur if: 
• no subject in the most recent cohort required dose reduction for purposes of managing 
AEs and/or laboratory abnormalities;  
• there is no resolution of any ≥ Grade 3 AE to Grade 1 or baseline within 10 days. 
AEs for dose increment decisions must be treatment-emergent and considered at least possibly 
related to KZR-261. 
Lower dose increases (ie, 25% increase or 1.25 × current dose) may be considered based on the 
frequency and severity of AEs not described above that are at least possibly related to KZR-261.  
If a DLT necessitates enrollment of additional subjects into a cohort, all safety data for that 
cohort will be reviewed after the additional subjects have completed the DLT assessment period. 
Based on evaluation of the data, the SRC and/or Sponsor may decide to enroll subjects at a 
KZR-261 dose level that is intermediate between the previous and the next higher planned dose.  
If a slot within the current dose escalation cohort is not available, additional subjects may be 
treated at a lower dose level deemed by the SRC to be safe and adequately tolerated. Subjects 
with malignant melanoma, malignant mesothelioma, mCRPC, or mCRC are preferred but not 
required for backfilling. 
The SRC can recommend enrollment of additional subjects at the putative MTD or MAD dose 
level to further assess safety at this dose. 
3.2.2. 
Intra-subject Dose Escalation 
Intra-subject dose escalation will be permitted after consultation with the Medical Monitor and in 
the following circumstance only: 
• Subject must have completed at least two 28-day cycles of treatment (Cycles 1 and 2).  
• Subject who experienced an AE* ≤Grade 3 with resolution to Grade 1 or baseline in the 
setting of a documented tumor response or stable disease over 2 consecutive assessment 
timepoints. For subjects who experienced a Grade 3 AE, the Investigator and Medical 
Monitor should come to an unequivocal consensus that the potential benefit of an 
increase in dose is likely to outweigh the risks. 
• Subject must not have experienced a DLT. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
37 
CONFIDENTIAL 
• Subject must not have experienced a dose reduction for purposes of managing AEs 
and/or laboratory abnormalities. 
• The higher dose cohort to which the subject would be escalated has been deemed by the 
SRC to be safe and adequately tolerated. 
* AEs must be assessed as unrelated to study treatment, such as intercurrent illness or 
concomitant medication. AEs that are assessed as related to study treatment would disqualify a 
patient from dose escalation. 
3.2.3. 
Definition of Dose-Limiting Toxicity for Part 1 
A DLT is defined as an AE or abnormal laboratory value that occurs during the first 28 days of 
treatment (Cycle 1) and meets the criteria listed below, unless it is assessed to be related to the 
disease under study, intercurrent illness, or concomitant medications. 
Toxicities will be assessed by the Investigator using the NCI CTCAE v5.0. AEs that are not 
listed in the NCI CTCAE are to be assessed using the criteria in Section 9.1.2. The attribution of 
an AE is to be assessed by the Investigator using the criteria in Section 9.1.3. 
Subjects who experience a DLT in Part 1, Cycle 1 must be withdrawn from study treatment and 
will not be replaced.  Subjects enrolled in Part 1 who discontinue from study treatment for 
reasons other than a DLT prior to completion of the DLT assessment period (Section 3.2.3) may 
be replaced. AEs that meet the definition of a DLT that are reported after Cycle 1 will be taken 
into consideration for dose escalation decisions and to help determine the dose for further 
investigation in Part 2. 
Subjects who do not experience a DLT in Part 1, Cycle 1 (Dose Escalation) must receive all of 
their scheduled doses (Days 1, 8, and 15) with completed follow-up data available through 
28 days of Cycle 1 to be eligible for DLT assessment. Subjects in Part 1, Cycle 1 who miss a 
dose for non-AE-related reasons will be replaced. 
Both hematologic and non-hematologic DLTs include the following: 
• Any AE that prevents the subject from receiving all planned doses during Cycle 1 
(Doses may be held up to 7 days for resolution of non-DLT toxicity).  
• Any AE that delays the initiation of Cycle 2 by >7 days because the AE has not 
resolved per criteria required for initiation of a new cycle (Section 6.1.2 and 
Section 6.1.4).  
Hematologic DLTs include the following:  
• Grade 3 or 4 neutropenia (absolute neutrophil count [ANC] <1.0 × 109/L) with a 
single temperature of >101°F (38.3°C), or microbiologically or radiographically 
documented infection. 
• Grade 4 neutropenia (ANC <0.5 × 109/L) in the absence of fever or infection lasting 
>7 consecutive days (complete blood count with differential must be measured every 
2 to 3 days until recovery of ANC to ≤Grade 2). 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
38 
CONFIDENTIAL 
• Grade 4 thrombocytopenia (platelet [PLT] count <25 × 109/L) lasting >7 days 
(platelet counts must be measured every 2 to 3 days until recovery to ≤Grade 2 
thrombocytopenia). 
• Grade 3 or 4 thrombocytopenia (PLT count <50 × 109/L) associated with clinically 
significant bleeding requiring platelet transfusion. 
Non-hematologic DLTs include the following: 
• Any non-hematologic AE ≥Grade 3, except the following: 
− Nausea, vomiting, diarrhea, electrolyte/metabolic abnormalities, constipation, 
fever, fatigue, or skin rash that resolves to ≤Grade 2 within 72 hours in the setting 
of optimal supportive care. 
− Grade 3 elevation in amylase or lipase without clinical or imaging manifestations 
of acute pancreatitis. In contrast, Grade 4 elevation in amylase or lipase and 
symptomatic Grade 3 lipase or amylase elevation are considered DLTs. 
• Clinical signs and symptoms of acute pancreatitis. 
• Drug-induced liver injury (Hy’s law), including all of the following: greater than 
3 × ULN elevation in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT), total bilirubin >2 × ULN in the absence of findings of 
cholestasis (ie, absence of alkaline phosphatase elevation to >2 × ULN) AND no 
other etiology to explain the combination of increased ALT/AST and total bilirubin. 
• FBS >200 mg/dL on 2 consecutive measurements, at least 24 hours apart, over a 
7-day period. In the DLT assessment period, subjects who experience FBS 
>200 mg/dL must have testing repeated within 7 days.  
3.2.4. 
Definition of Maximum Tolerated Dose, Maximum Administered Dose, and 
Recommended Phase 2 Dose 
The estimated MTD is the dose level associated with approximately 30% of DLT-evaluable 
subjects experiencing a DLT. The target interval for the DLT rate is 25%-35%. Due to the 
discreteness of the dose levels and in the interest of the safety of subjects, the estimated MTD is 
the highest tested dose level with a DLT rate 35% in at least 6-12 DLT-evaluable subjects. In 
general, the highest dose in Part 1 that provides an acceptable safety profile (MTD or MAD) will 
also be the highest dose tested in Part 2 unless one or more of the following suggest that an 
alternate (ie, lower) dose would be preferable: 
• Clinically significant anti-tumor effects observed at a lower dose. 
• The frequent occurrence of late and relevant AEs that occur after the DLT period. 
The MAD is declared without an MTD based on the highest dose level with an observed DLT 
rate <25% (the lower bound of the MTD range) and where sufficient safety and efficacy signals 
have been observed. 
The RP2D is the dose chosen for further study based on assessment of a favorable benefit-risk 
profile across the totality of Phase 1 study results, including both Parts 1 and 2. The RP2D will 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
39 
CONFIDENTIAL 
take into account late and relevant toxicities that occur after the DLT assessment period in Part 1 
and/or the safety/tolerability of multiple cycles of treatment. 
3.3. 
Part 2A: Dose Expansion 
Following determination of the MTD/MAD, separate tumor-specific cohorts of subjects will be 
treated with KZR-261. For all subjects enrolled in a tumor-specific cohort, tumor biopsies (fresh 
[preferred] or archived) will be requested pre-treatment. For any subject who provides a tumor 
sample pre-treatment, an additional biopsy of accessible tumor tissue will be requested at either 
the end of Cycle 2 or at PD, whichever comes first. Pre-treatment tumor biopsies (fresh) will be 
required for subjects enrolled in the All-Tumors expansion cohort (exceptions to this requirement 
may be considered after discussion with the Medical Monitor); an additional biopsy of accessible 
tumor tissue will be required at either the end of Cycle 2 or at PD, whichever comes first. 
Fifteen subjects will be enrolled in each tumor-specific cohort (Stage 1), which may be increased 
up to 35 subjects in total as determined by prespecified futility criteria in Stage 1 (Section 10.6) 
and if the tumor type is not selected for investigation in Part 2B. Up to 35 biopsy-evaluable 
subjects may be enrolled in the All-Tumors cohort. 
The following distinct dose expansion cohorts may be evaluated, as depicted in Figure 1.  
Tumor-Specific Cohorts 
• Malignant melanoma—histologically or cytologically confirmed, locally advanced 
unresectable or metastatic cutaneous or uveal melanomas (Section 4.2). 
• Malignant mesothelioma—histologically or cytologically confirmed that is either 
metastatic or locally advanced and not amenable to surgical resection or local 
therapies (Section 4.2). 
• mCRPC—histologically or cytologically confirmed, locally advanced unresectable 
or metastatic adenocarcinoma of the prostate that is castration (physical or chemical) 
resistant(Section 4.2). 
• mCRC—histologically or cytologically confirmed, metastatic or locally advanced 
unresectable colorectal carcinoma (Section 4.2). 
All-Tumors Cohort 
• All-Tumors—any relapsed or refractory solid tumors that are amenable to tumor 
biopsies (Section 4.2). 
Additional (or different) tumor types may be investigated at the Sponsor’s discretion in Part 2 if 
evidence of anti-tumor activity of KZR-261 during Part 1 or in the All-Tumors cohort in Part 2 
supports further evaluation. 
3.4. 
Part 2B: Dose Optimization 
Dose optimization in tumor-specific cohorts may be initiated at the Sponsor’s discretion based 
on the totality of data after the MTD/MAD has been determined. The Sponsor may also choose 
to cease enrollment in Part 2A and initiate enrollment of that tumor type in Part 2B. 
Approximately 30 subjects in each Part 2B cohort will be randomized 1:1 to treatment with 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
40 
CONFIDENTIAL 
KZR-261 at the MTD/MAD or a lower clinically active dose. Based on additional safety data 
from Part 2A, the sponsor may convene an SRC meeting to determine whether a lower dose than 
the MTD/MAD as determined in Part 1 should be evaluated in Part 2B. 
As in Part 2A, subjects enrolled in Part 2B will be requested to provide pre-treatment tumor 
tissue (fresh [preferred] or archived). For subjects who provide a tumor sample pre-treatment, a 
biopsy of accessible tumor tissue will be requested at either the end of Cycle 2 or at PD, 
whichever comes first. 
3.5. 
Safety Review Committee (Parts 1, 2A, and 2B) 
The SRC will consist of the Medical Monitor (or designate), other Kezar representative(s), and 
participating Investigators. All Investigators who enroll subjects in the cohort under review will 
be consulted prior to the SRC meeting if they are unable to attend the scheduled meeting.  
During Part 1, the committee will review safety data from the current cohort and previous 
cohorts before deciding on escalation to the next dose level. Dose escalation may occur only 
after the SRC has agreed (Section 3.2.1.1).  
The totality of safety data from Part 1 will be reviewed prior to a declaration of the MTD/MAD. 
Available PK data may also be reviewed. 
During Parts 2A and 2B, the SRC will periodically monitor safety data through the end of the 
study.  
In Part 2, the study will be halted if there is one Grade 5 or two Grade 4 AEs in different subjects 
that are considered at least possibly related to KZR-261. Exceptions to the halting criteria 
include asymptomatic Grade 4 laboratory abnormalities (eg, neutropenia) that resolve either with 
or without routine supportive care measures and without sequelae. If this scenario occurs, a 
formal safety analysis will be conducted, and the findings will be submitted to the IND for the 
FDA to review prior to enrolling additional subjects. 
A separate SRC Charter will describe the responsibilities of this committee for both dose 
escalation and dose expansion/dose optimization. 
3.6. 
Planned Duration of Subject Participation (Parts 1, 2A, and 2B) 
The study comprises a 4-week Screening Period, a Treatment Period lasting approximately 
24 weeks (6 cycles, 4 weeks each), a 30-day Safety Follow-up Period, and a 12-month 
Long Term Follow-up Period (after last dose of study treatment), for a total study duration of 
approximately 20 months. Upon completion of Cycle 6, a subject who is deriving clinical benefit 
may continue treatment at the discretion of the Investigator and with agreement of the Medical 
Monitor. 
3.7. 
Number of Planned Sites 
Approximately 8 sites are planned for the Dose Escalation part of the study (Part 1), up to 
approximately 12 additional sites may participate in Dose Expansion and Dose Optimization 
(Part 2). 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
41 
CONFIDENTIAL 
4. 
SUBJECT SELECTION 
4.1. 
Number of Planned Subjects 
Approximately 70 subjects will be enrolled and treated in Part 1 (Dose Escalation) of KZR-261. 
The principal determinants of the total number of subjects will depend on the number of dose 
levels of KZR-261, the number of subjects per dose level, and the number of subjects treated at 
the MTD or the MAD(s). In Part 2A (Dose Expansion), up to 175 subjects will be enrolled 
(Section 3.3). In Part 2B (Dose Optimization), up to 120 subjects (30 per tumor-specific cohort 
[15 per dose level]) will be enrolled into up to 4 tumor-specific cohorts (Section 3.4). 
4.1.1. 
Subject Screening 
Study participation begins once written informed consent is obtained (see Section 11.3 for 
details). The Investigator will ensure that each subject has provided written informed consent 
before performing any study-related assessments unless the procedure or assessment is consistent 
with the standard of care for the underlying malignancy. 
Once informed consent is obtained, each subject will be assigned a sequential identification 
number and undergo screening evaluations to assess study eligibility (inclusion/exclusion 
criteria). The subject identification number will be used to identify the subject during the 
screening process and throughout study participation. 
Screening assessments for this study should be performed between Day –28 and Day –1 (see the 
Schedule of Events, Appendix A). All subjects will be reviewed and approved by the Medical 
Monitor prior to enrollment. Subjects may be re-screened one time, if needed, with the Sponsor’s 
approval. Subjects who have failed 1 or more screening assessments may be re-tested for that 
assessment(s) within the designated 28-day time frame for final eligibility determination. 
Screening data will be captured in the electronic case report form (eCRF). 
4.2. 
Inclusion and Exclusion Criteria 
Only patients who fulfill all the inclusion criteria and none of the exclusion criteria may be 
enrolled into the study. For enrollment in Parts 2A or 2B (Dose Expansion or Dose 
Optimization), subjects must meet additional tumor-specific criteria outlined in Section 4.2.2 to 
be considered eligible for study participation. 
4.2.1. 
Inclusion Criteria 
1. Age ≥18 years. 
2. Willing and able to sign informed consent before initiation of any study-specific 
procedures or treatment. 
3. Histologic or cytologic evidence of a malignant solid tumor (except primary central 
nervous system [CNS] neoplasms), either metastatic or locally advanced and not 
amenable to surgical resection or other locoregional therapies. 
4. Disease that is resistant to or relapsed following available standard systemic therapy, or 
for which there is no standard systemic therapy, or refused such therapies if available. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
42 
CONFIDENTIAL 
Documentation of the reason must be provided for subjects who have not received a 
standard therapy likely to result in clinical benefit. 
5. ECOG PS score of 0 or 1. 
6. Adequate baseline hematologic function: 
a. ANC ≥1.5 × 109/L. Myeloid growth factors must not have been administered within 
7 days before the first dose of KZR-261. 
b. Hemoglobin ≥8 g/dL and no red blood cell (RBC) transfusions during the 14 days 
before the first dose of KZR-261.  
c. PLT count ≥100 × 109/L and no platelet transfusions during the 14 days before the 
first dose of KZR-261.  
7. Adequate baseline organ function, as demonstrated by the following: 
a. Serum creatinine ≤1.5 × ULN (local institution) or calculated creatinine clearance 
≥60 mL/min by the Cockcroft-Gault formula. 
b. Serum albumin ≥2.5 g/dL. 
c. Bilirubin ≤1.5 × ULN (local institution). 
d. AST and ALT ≤2.5 × ULN (local institution). Subjects with hepatic metastases may 
have ALT and AST ≤5 × ULN. 
8. Serum amylase and lipase values <1.5 × ULN (local institution). 
9. FBS <200 mg/dL. 
10. Fasting triglycerides <300 mg/dL. 
11. International normalized ratio (INR) ≤1.5 or prothrombin time (PT) ≤1.5 × ULN (local 
institution); and either partial thromboplastin time (PTT) or activated partial 
thromboplastin time (aPTT) ≤1.5 × ULN. Exceptions are allowed for patients receiving 
therapeutic anticoagulation for a history of thrombosis. Note: Anticoagulation with 
warfarin is exclusionary. 
12. Female subjects must have negative serum β-human chorionic gonadotropin (β-hCG) test 
results during Screening and negative serum or urine pregnancy test results, whichever is 
preferred, at Baseline if the subject is a woman of childbearing potential (WOCBP), 
defined as a woman who has not undergone a hysterectomy or bilateral oophorectomy or 
has not been naturally postmenopausal for at least 24 consecutive months. 
13. Subjects who are WOCBP must agree to use highly effective contraceptive methods or 
abstinence for the duration of time on the study and continue to use acceptable 
contraceptive methods for 3 months after administration of the last dose of study 
treatment. Highly effective contraception is defined as use of the 2-barrier method (eg, 
female diaphragm and male condom) or 1 barrier method with spermicide, intrauterine 
device, or hormonal contraceptives (eg, implant or oral). If the subject is using a 
hormonal form of contraception, use must have been stable for at least 4 weeks prior to 
Screening. Abstinence will be acceptable only if it is in line with the preferred and usual 
lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation) and withdrawal are 
not acceptable methods of contraception. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
43 
CONFIDENTIAL 
14. Male subjects with female partners of childbearing potential must be congenitally or 
surgically sterile (vasectomy with confirmation of aspermia) or agree to use 2 effective 
methods of contraception including one barrier method (eg, condom with spermicide) and 
contraception by the female partner for the duration of time on the study and for 3 months 
after administration of the last dose of study treatment. Use of a condom is required by 
men during intercourse with a male or female partner to prevent potential delivery of the 
drug via seminal fluid during the study until the End of Treatment visit. 
15. The subject agrees to, and is capable of, adhering to the study visit schedule and other 
protocol requirements, including follow-up for survival. 
16. Willing and able to comply with the requirements of the protocol. 
17. Disease that is measurable by standard imaging techniques according to RECIST v1.1 
(Eisenhauer et al., 2009). For subjects with prior radiation therapy, measurable lesions 
must be outside of any prior radiation field(s), unless disease progression has been 
documented following radiation to the site. 
4.2.2. 
Additional Inclusion Criteria for Parts 2A and 2B (Dose Expansion and Dose 
Optimization) 
All subjects considered for enrollment into Part 2 of the study must meet the following criteria in 
addition to the criteria listed in Section 4.2.1:  
18. Subjects who agree to submit fresh or archived tumor tissue must do so during the 
Screening period tissue.  
19. For subjects who have cutaneous melanoma: 
a. Must have histologic or cytologic evidence of disease that is locally advanced or 
metastatic (American Joint Committee on Cancer [AJCC] Stage 3 or 4). 
b. Must have relapsed or be refractory to treatment with currently approved therapies, 
including an immune checkpoint inhibitor(s), or unable to tolerate approved therapy(ies). 
c. For subjects with a RAF V600 mutation, the subject may have received therapy with 
a small molecule RAF V600 inhibitor with or without a small molecule MEK 
inhibitor. 
20. For subjects who have uveal melanoma: 
a. Must have histologic or cytologic evidence of locally advanced unresectable or 
metastatic uveal melanoma.  
b. Disease must be treatment naive or have progressed (radiologically or clinically) on 
most recent therapy. 
21. For subjects who have malignant mesothelioma of the peritoneum or pleura: 
a. Must have histologic or cytologic evidence of malignant mesothelioma that is either 
metastatic or locally advanced and not amenable to surgical resection or treatment 
with localized therapies. 
b. Must have been previously treated with an acceptable platinum-based regimen 
(eg, cisplatin or carboplatin combined with pemetrexed).  

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
44 
CONFIDENTIAL 
c. The subject may have received Tumor Treating Fields (TTFields).  
d. Has previously received treatment with an approved immunotherapy unless the 
subject is not a candidate for immunotherapy. 
22. For subjects who have mCRPC:  
a. Must have histologically or cytologically documented, locally advanced unresectable 
or metastatic adenocarcinoma of the prostate. 
b. Must have disease progression despite castration by orchiectomy or ongoing 
luteinizing hormone-releasing hormone (LHRH) analogue. 
c. Must have disease that progressed on or after treatment with androgen inhibitors. 
d. Must have prior treatment with a taxane or not be a candidate for treatment with a 
taxane. 
e. Must have prior treatment with an inhibitor of poly ADP-ribose polymerase (PARP) 
if the subject has a deleterious germline or somatic BRCA 1/2 mutation or another 
homologous recombination repair gene mutation.  
f. Must have progressive disease as defined by PCWG3 criteria (Scher et al., 2016). 
Note: Patients with biochemical progression (ie, rising PSA levels) only are not 
eligible. 
g. Must have measurable or evaluable disease. Eligible subjects must have at least one 
measurable lesion per RECIST v1.1 and/or evidence of relapse/progression in bone 
per PCWG3. 
23. For subjects who have mCRC:  
a. Must have histologic or cytologic evidence of CRC that is locally advanced and 
unresectable or metastatic. 
b. Must have received or demonstrated intolerance to, appropriate therapy consisting of 
a fluoropyrimidine-based regimen with oxaliplatin and/or irinotecan with or without a 
therapeutic targeting VEGF, and with a monoclonal antibody (mAb) targeting EGFR, 
if their tumor lacks a KRAS mutation.  
c. If the subject has a tumor with a RAF V600 mutation, the subject must have received, 
or demonstrated intolerance to, appropriate therapy targeting RAF V600 with or 
without a small molecule MEK inhibitor plus a mAb targeting EGFR.  
d. If the subject has a tumor that is microsatellite instability high (MSI-H), the subject 
must have received or demonstrated intolerance to therapy targeting PD-1. 
e. Must have received no more than 4 prior lines of therapy for mCRC (adjuvant therapy 
does not count as a line of treatment). 
24. For subjects who have relapsed or refractory solid tumors in the All-Tumors cohort 
(Part 2A), excluding primary CNS malignancies.  
a. Must be able to submit fresh tumor tissue during the Screening period. Exceptions to 
this requirement may be considered after discussion with the Medical Monitor. 
b. Appendix C includes a list of prioritized tumor types. 
4.2.3. 
Exclusion Criteria 
Subjects who meet any of the following criteria at Screening will not be enrolled in the study: 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
45 
CONFIDENTIAL 
1. Subjects who have participated in Part 1 dose escalation are not eligible to enroll in Part 
2A dose expansion or Part 2B dose optimization.  
2. Persistent clinically significant toxicities (≥Grade 2 per NCI CTCAE version 5.0) from 
previous anticancer therapy (excluding alopecia). 
3. Treatment with any systemic anti-cancer therapy within 14 days or treatment with a 
biologic within 28 days before the first dose of KZR-261. 
4. Treatment with an investigational drug within 14 days or treatment with a biologic within 
28 days before the first dose of KZR-261.  
5. Radiation therapy within 14 days before the first dose of KZR-261. 
6. History of prior radiation to the pancreas. 
7. History of diabetes that is not well-controlled. 
8. History of symptomatic gallstones not treated with cholecystectomy within 5 years of 
Screening. For patients with a history of gallstones treated with cholecystectomy, 
diagnosis of bile duct stones within 3 years of Screening. 
9. Major surgical procedure within 28 days before the first dose of KZR-261. Interventional 
procedures such as percutaneous catheters for drainage of an effusion or central line 
placement may be permitted following consultation with the Medical Monitor, unless the 
central line placement is for study treatment. 
10. A history of familial hypertriglyceridemia. 
11. A personal or family history of acute or chronic pancreatitis from any cause. 
12. A diagnosis of Sjogren’s syndrome. 
13. Heavy alcohol use as defined by the Centers for Disease Control and Prevention: 
≥15 alcoholic drinks for males or ≥8 alcoholic drinks for females per week. 
14. Additional active malignancy that may confound assessment of the study endpoints. 
Subjects with the following concomitant malignancies are eligible: nonmelanoma skin 
cancer and carcinoma in situ (including transitional cell carcinoma, cervical cancer, anal 
carcinoma, and melanoma in situ). Subjects with a history of other secondary 
malignancies (ie, active malignancy within 2 years before study entry) with a low risk of 
recurrence may be discussed with the Sponsor for consideration of enrollment. 
15. Clinically significant cardiovascular disease including, but not limited to, the following: 
a. Uncontrolled or any New York Heart Association Class III or IV congestive heart 
failure. 
b. History of myocardial infarction, unstable angina, or stroke within 6 months before 
study entry. 
16.  Hypertension or clinically significant arrhythmias not adequately controlled by 
medication. 
17. Corrected QT (QTc) interval by Fridericia’s formula (QTcF) on resting ECG at Screening 
or Baseline >470 msec. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
46 
CONFIDENTIAL 
18. History of risk factors for Torsades de pointes (eg, heart failure, hypokalemia, family 
history of long QT syndrome). 
19. Uncontrolled, clinically significant pulmonary disease (eg, chronic obstructive pulmonary 
disease, pulmonary hypertension) that, in the opinion of the Investigator, would put the 
subject at significant risk for pulmonary complications during the study (subject must not 
require supplemental oxygen). 
20. Active, symptomatic CNS metastases. Any surgery or radiation therapy administered for 
the treatment of CNS metastases must have been completed at least 28 days the date of 
informed consent with a follow-up magnetic resonance imaging (MRI) demonstrating no 
progression of previously active lesions. Patients requiring corticosteroids must be on a 
stable or decreasing dose for 4 or more weeks prior to the first dose of KZR-261. 
21. Primary CNS malignancy. 
22. Condition requiring systemic treatment with either corticosteroids (>20 mg daily 
prednisone equivalents) or other immunosuppressive medications within 14 days before 
the first dose of KZR-261. Inhaled or topical steroids and adrenal replacement doses ≤20 
mg daily prednisone equivalents are permitted. 
23. Uncontrolled intercurrent illness including, but not limited to, medical illness that has the 
potential to prevent the patient from completing the first response assessment at the end 
of Cycle 2 as well as psychiatric illness, or social situations that would limit compliance 
with study requirements. 
24. Known positive status for human immunodeficiency virus (screening is not required). 
25. History of active or chronic hepatitis B or C. Subjects who are HBsAg negative and 
hepatitis B core antibody positive with no detectable HBV DNA at Screening will be 
allowed into the study and will require regular monitoring for hepatitis B virus DNA. 
Subjects with a history of hepatitis C should have received curative treatment and exhibit 
absence of detectable HCV RNA at Screening. 
26. Any medical condition that, in the opinion of the Investigator, places the subject at 
unacceptably high risk. 
27. Treatment with warfarin.  
28. Concomitant medications that would need to be taken during the course of the study as 
defined in Section 6.2.2. 
29. Women who are pregnant, lactating, or discontinued lactation less than 12 weeks prior to 
Screening, or who plan to become pregnant or initiate lactation during the study. 
30. Unable to comply with the protocol in the Investigator’s or Sponsor’s opinion. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
47 
CONFIDENTIAL 
5. 
STUDY DRUG 
Instructions for the receipt, inspection, storage, preparation, administration, and disposal of 
KZR-261 will be provided in a separate Pharmacy Manual to each clinical site. 
5.1. 
KZR-261 
5.1.1. 
Physical Description of KZR-261 
KZR-261 is a small molecule protein secretion inhibitor formulated for clinical use as 
 
KZR-261 for Injection is a lyophilized drug product that is supplied in vials delivering 75 mg of 
KZR-261 
. Each vial is 
reconstituted with sterile Water for Injection prior to administration. 
5.1.2. 
Packaging and Labeling of KZR-261 
The drug product will be supplied in a single-use glass vial delivering 75 mg of KZR-261 and 
packaged in single vial cartons. 
The Sponsor or its representatives will be responsible for labeling according to local regulatory 
requirements.  
All packaging and labeling operations will be performed according to Good Manufacturing 
Practice for Medicinal Products (GMP) and the relevant regulatory requirements. 
5.1.3. 
Supply, Dispensing, Storage, and Study Drug Accountability for KZR-261 
Refer to the Pharmacy Manual for storage conditions of KZR-261. The Sponsor or its 
representatives will supply KZR-261 to the investigational sites. The study drug supplies 
provided for this study will be manufactured under current GMPs, will be subject to release, and 
will be suitable for human use. 
The Investigator (or designate) must confirm that appropriate temperature conditions have been 
maintained during transit for all investigational product received and any discrepancies have 
been reported and resolved before use of the investigational drug product. 
Only subjects enrolled in the study may receive study drug, and only authorized site staff may 
supply or administer study drug. All study drug should be stored in an environmentally 
controlled and monitored (manual or automated) area in accordance with the labeled storage 
conditions. Access to study drug must be limited to the Investigator and authorized site staff. 
Further information on the storage, preparation, and administration of study drug will be 
provided in the Pharmacy Manual. 
On receipt of the study drug, the Investigator (or designate) will conduct an inventory of the 
supplies and verify that study drug supplies are received intact and in the correct amounts. 
The study monitor may check the study supplies at each study center at any time during the 
study. 
The Investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study drug accountability, reconciliation, and record maintenance (such as 
receipt, reconciliation, and final disposition records). 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
48 
CONFIDENTIAL 
It is the responsibility of the study monitor to ensure that the Investigator (or designate) has 
correctly documented the amount of the study drug received, dispensed, and returned on the 
dispensing log that will be provided. A full drug accountability log will be maintained at the 
study center at all times. The study monitor will perform an inventory of study drug at the 
closeout visit to the study center. All discrepancies must be accounted for and documented. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
49 
CONFIDENTIAL 
6. 
DOSAGE AND TREATMENT ADMINISTRATION 
6.1. 
Treatment Administration 
For all subjects, KZR-261 will be administered as a 30- to 60-minute IV infusion via a central 
line on Days 1, 8, and 15 of a 4-week (28-day) treatment cycle. An IV infusion pump or syringe 
pump will be used for all infusions. 
Further details regarding drug product formulation, preparation, and administration of KZR-261 
will be provided in a separate Pharmacy Manual.  
6.1.1. 
Monitoring of Dose Administration 
Study treatment will be administered on an outpatient basis. Subjects should remain at the study 
site for observation for 6 hours following the first cycle, first dose (Cycle 1 Day 1) and for 
2 hours following study treatment administration for the rest of Cycle 1 (Cycle 1 Days 8 and 15). 
For Cycle 2, subjects will be under observation for 1 hour following study treatment. For Cycle 3 
and beyond, there is no required post-infusion monitoring.  
This is a FIH study; therefore, treatment modifications for AEs may change as data are accrued. 
Subjects experiencing unacceptable AEs should have their treatment interrupted until resolution 
(Section 6.1.2 and Section 6.1.4). Treatment with KZR-261 can then be reinitiated after 
consultation with the Medical Monitor.  
6.1.2. 
Criteria for Interrupting Treatment During a Treatment Cycle 
Within a treatment cycle, KZR-261 should be withheld on any scheduled treatment day if, during 
the previous 24 hours, the subject experiences any of the following events:  
• ≥Grade 2 diarrhea, despite optimal anti-diarrheal therapy 
• ≥Grade 2 vomiting, despite optimal anti-emetic therapy 
• ≥Grade 3 fatigue that is not relieved by rest and limits self-care activities 
• ≥Grade 3 transaminase elevation 
• ≥Grade 2 amylase 
• FBS ≥200 mg/dL 
• PLT count <50 × 109/L 
• ANC <0.5 × 109/L 
• Average QTcF >500 msec 
• No resolution to ≤Grade 2 or baseline of previously reported Grade 3 or 4 events 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
50 
CONFIDENTIAL 
6.1.3. 
Criteria for Initiation of a New Cycle 
To commence treatment in Cycle 2 and beyond, subjects must meet the following criteria: 
• ANC ≥1.25 × 109/L 
• Hemoglobin ≥8 g/dL 
• PLT count ≥75 × 109/L 
• Serum creatinine ≤1.5 × ULN (local institution) or calculated creatinine clearance 
>60 mL/min by the Cockcroft-Gault formula 
• Total bilirubin ≤1.5 × ULN (local institution) 
• AST and ALT ≤3 × ULN (local institution) or ALT and AST ≤5 × ULN if the subject 
has hepatic metastases 
• FBS <200 mg/dL 
• Serum amylase and lipase values ≤1.5 × ULN (local institution) 
• Average QTcF <470 msec 
• Resolution to ≤Grade 2 or baseline of any previously reported Grade 3 or 4 event 
6.1.4. 
Dose Modification Guidelines for KZR-261 
Dose reductions are not permitted during Cycle 1 (DLT assessment period) of Part 1 (Dose 
Escalation). If a subject experiences an event that qualifies as a DLT, as defined in Section 3.2.3, 
the subject must be discontinued from study treatment and followed for resolution of AEs as 
described in Section 9.1.5. Doses may be withheld or reduced for specific AEs and/or laboratory 
abnormalities in Cycles 2+ for subjects participating in Part 1 and in all cycles for subjects in 
Part 2 (Section 6.1.4.2). 
Withheld doses should not be made up (Section 6.1.5).  
6.1.4.1. 
Dose Interruptions 
Subjects who experience an AE at any time during the study may interrupt study treatment per 
Section 8.1. Subjects must continue to fulfill all criteria outlined in Section 6.1.3 and not fulfill 
any of the criteria outlined in Section 6.1.2 prior to each dose. 
6.1.4.2. 
Dose Modifications for Toxicity 
Outside the DLT assessment period, dose modifications are to be discussed with the Medical 
Monitor prior to implementation to determine whether a dose modification is recommended. 
If KZR-261 is withheld for any toxicity within a treatment cycle, KZR-261 may be resumed 
within that cycle pending fulfillment of the criteria in Section 6.1.2 to Grade 1 or baseline, 
platelet counts to Grade 2 without clinical bleeding, or absolute neutrophil counts to Grade 2 
prior to the next scheduled treatment.  
Table 2 through Table 7 summarize guidelines for KZR-261 treatment modifications for various 
potential toxicities encountered. The dose modifications detailed in these tables are based on 
toxicities encountered within a cycle to determine the most appropriate dose for initiation of a 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
54 
CONFIDENTIAL 
6.2.1. 
Permitted Concomitant Medications 
6.2.1.1. 
Concurrent Supportive Care 
Hematopoietic growth factors (eg, thrombopoietic agents such as romiplostim and eltrombopag, 
erythropoiesis stimulating agents, or granulocyte colony stimulating factors such as filgrastim 
and pegfilgrastim) are not permitted during Cycle 1 (the DLT assessment period, Section 3.2.3) 
for subjects in Part 1 (Dose Escalation) unless they are required for treatment of a DLT. In 
Cycles 2 and beyond, hematopoietic growth factors are permitted and may be used as clinically 
warranted and following institutional policies and recommendations. In case of severe or febrile 
neutropenia, growth factors may be used until neutrophil count recovery. In Part 2, 
hematopoietic growth factors may be used in Cycle 1 based on agreement between the 
Investigator and the Medical Monitor and in Cycles 2+ as per the aforementioned guidelines for 
Part 1. 
Comprehensive supportive care is permitted during the study, including but not limited to 
anti-emetic and anti-diarrheal agents, appetite stimulants, stimulants with wakefulness-promoting 
properties (eg, modafinil), anticachexia therapy (eg, fish oil supplements), antidepressants, opiate 
and non-opiate analgesics, antibiotics, selective use of corticosteroids (≤20 mg daily prednisone 
or prednisone equivalent), therapies for diabetes mellitus, and platelet/neutrophil growth factors 
as indicated above. Anticoagulants except warfarin are also permitted. 
Subjects with mCRPC are expected to continue on LHRH analogues if ongoing at Screening.  
6.2.1.2. 
Other Concomitant Medications 
Hormonal contraception is allowed. If using a hormonal form of contraception, use must have 
been stable for at least 4 weeks prior to Screening (Section 4.2.1). The same hormonal 
contraception should be continued for the duration of the study. If hormonal contraception is 
discontinued for safety reasons, the Investigator should ensure that the subject is using another 
acceptable form of contraception. 
KZR-261 may affect medications that are substrates of CYP3A4. Administration of sensitive 
substrates of CYP3A4, or narrow therapeutic index drugs that are metabolized by CYP3A4 is not 
recommended from 14 days prior to the first dose of KZR-261 and during study treatment. If no 
alternative is available, please refer to the respective prescribing labels for dosing instructions. 
Medications that are sensitive substrates of CYP3A4, defined as those whose exposure may 
increase >5-fold in the presence of CYP3A4 inhibition, are listed in Appendix D. 
6.2.2. 
Prohibited Concurrent Medications/Therapies 
While receiving treatment with KZR-261, enrolled subjects may not receive investigational or 
approved anticancer agents including cytotoxic chemotherapy, targeted therapies, or therapeutic 
monoclonal antibodies. 
Palliative radiation is permitted only for symptom management and with a narrow radiation port 
(eg, solitary bone lesion). Sponsor review and approval is required before administration of 
palliative radiation while on study treatment. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
55 
CONFIDENTIAL 
7. 
STUDY PROCEDURES 
7.1. 
Schedule of Study Procedures 
Schedules of study procedures for the Screening Period, Treatment Period, and the Follow-up 
Period (including visit windows) are presented in the Schedule of Events (Appendix A and 
Appendix B).  
Details regarding the specific blood draw requirements for each visit are outlined in the 
Laboratory Manual provided to each study site. 
7.2. 
Description of Study Procedures 
Prior to undergoing any study-specific procedures/assessments (except those consistent with 
standard of care for management of the underlying malignancy), all potential subjects must sign 
an informed consent form (ICF) describing the study with sufficient information for subjects to 
make an informed decision regarding their participation per Section 11.3. 
The following sections provide details of the procedures to be performed.  
7.2.1. 
Medical History 
Documentation of the subject’s medical history should contain the subject’s full medical history 
including prior and concomitant illnesses/diseases, concomitant medications, and demographic 
data. Historical cancer data and diagnostic information, including tumor mutational profile if 
known, will be captured in the eCRF. Prior imaging reports may be requested. 
7.2.2. 
Physical Examination 
A complete physical examination including collection of body weight will be conducted at 
Screening and Baseline and should include assessments of at least the following systems: head 
and neck, dermatological, respiratory, cardiovascular, abdomen, extremities, neurological, and 
musculoskeletal. Height will be collected at the Screening visit only. 
A symptom-directed abbreviated physical examination including collection of body weight will 
be conducted at all other study visits indicated in the Schedule of Events (Appendix A and 
Appendix B).  
Subjects will be asked at each visit that includes a physical examination about mouth dryness, 
salivary gland pain and sensitivity, and urinary and ejaculation issues. Treatment-emergent, 
medically significant changes from baseline in physical examination will be recorded as AEs.  
7.2.3. 
Pregnancy Testing and Reproduction Precautions 
Women of childbearing potential must have a negative serum β-hCG pregnancy test result at 
Screening. Negative serum or urine pregnancy tests will be required at all other visits indicated 
in the Schedule of Events (Appendix A and Appendix B). The Screening visit test should be 
performed within 2 weeks prior to initiation of study treatment or in closer proximity to the 
treatment start-date as required by local/institutional regulations. A positive urine pregnancy test 
result should be confirmed by a serum pregnancy test. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
56 
CONFIDENTIAL 
The subject must agree to use highly effective contraceptive methods or abstinence for the 
duration of time on the study and continue to use acceptable contraceptive methods for 3 months 
after administration of the last dose of study treatment. Highly effective contraception is defined 
as the use of 2-barrier methods (eg, female diaphragm and male condom) or 1 barrier method 
with spermicide, intrauterine device, or hormonal contraceptives (eg, implant or oral). If the 
subject is using a hormonal form of contraception, use must have been stable for at least 4 weeks 
prior to Screening, and if using concomitant mycophenolate, the subject must use another 
nonhormonal form of highly effective contraception. Abstinence will be acceptable only if it is in 
line with the preferred and usual lifestyle of the subject. Periodic abstinence (eg, calendar, 
ovulation) and withdrawal are not acceptable methods of contraception. 
Male subjects with female partners of childbearing potential must be congenitally sterile or 
surgically sterile (vasectomy with confirmation of aspermia) or agree to use 2 effective methods 
of contraception including one barrier method (eg, condom with spermicide and contraception by 
female partner) for the duration of time on the study and for 3 months after administration of the 
last dose of study treatment. Use of a condom is required by men during intercourse with a male 
or female partner to prevent potential delivery of the drug via seminal fluid during the study until 
the EOT visit. 
7.2.4. 
Electrocardiogram 
ECGs will be performed at the timepoints indicated in the Schedule of Events (Appendix A and 
Appendix B). Note that some study visits have pre-treatment and multiple post-treatment ECG 
timepoints. Additional ECGs are required during Cycle 4 (Appendix B). 
Vital sign measurements should be performed per institutional guidelines, preferably prior to 
ECGs. A 12-lead ECG is performed 10 minutes after the subject has been in the supine position. 
The Investigator or qualified designate will review and indicate if the ECG is normal or 
abnormal, and if abnormal, whether clinically significant. Any medically significant changes 
from the Screening ECG will be recorded as an AE.  
7.2.5. 
Vital Sign Measurements and Oxygen Saturation 
Vital signs measurements (including systolic and diastolic blood pressure, pulse rate, respiration 
rate, and body temperature) and oxygen saturation will be collected at all study visits. Blood 
pressure and pulse should be collected after the subject has had at least 5 minutes of rest in the 
seated position. If blood pressure is elevated on the first measurement at Screening or Baseline, it 
should be repeated after an additional 5 minutes of rest. It is recommended that blood pressure is 
measured using the same arm at each assessment. When the time of vital signs measurement 
coincides with a blood sample collection, vital signs will be measured per institutional 
guidelines. 
7.2.6. 
Ocular Examination 
Slit lamp and visual acuity examinations will be conducted to monitor for cataracts and should 
be reviewed prior to administration of KZR-261 at the beginning of each cycle where an eye 
examination is required (Appendix A and Appendix B). Any medically significant changes from 
the Screening evaluation will be recorded as an AE. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
57 
CONFIDENTIAL 
7.2.7. 
Tumor Specimens for Biomarkers 
Tumor biopsies will be requested pre-treatment. Although a fresh sample is preferred, 
submission of an adequate tumor specimen (paraffin block) collected within 1 year before the 
subject’s first dose of KZR-261 will be acceptable for subjects where a fresh sample cannot be 
obtained. If a paraffin block is not available, a minimum of 10 and up to 20 5-µm unstained 
slides should be provided. For any subject who provided a tumor sample pre-treatment, a biopsy 
of accessible tumor tissue will be requested at either the end of Cycle 2 (Days 21-28 of Cycle 2) 
or at PD, whichever comes first. 
Pre-treatment tumor biopsies (fresh only) will be required for subjects enrolled in the All-
Tumors expansion cohort in Part 2A (exceptions to this requirement may be considered after 
discussion with the Medical Monitor); an additional biopsy of accessible tumor tissue will be 
required at either the end of Cycle 2 (Days 21-28 of Cycle 2) or at PD, whichever comes first. 
7.2.8. 
Clinical Laboratory Evaluations 
Collection of blood and urine samples for clinical laboratory evaluations are outlined in the 
Schedule of Events for Cycles 1 and 2 (Appendix A) and Cycle 3+ (Appendix B).  
Clinical laboratory tests for safety (hematology, serum chemistries, urinalyses, coagulation tests, 
serum pregnancy) and other tests during scheduled visits will be performed at the clinical trial 
site or an alternative, licensed local testing facility. Pregnancy tests, urine or serum, may be 
performed at the study site using a licensed test. Abnormal safety laboratory results that are 
considered clinically significant should be repeated as soon as possible (preferably within 24–48 
hours).  
Subjects who are HBsAg negative and hepatitis B core antibody positive with no detectable 
DNA at Screening will require regular monitoring of hepatitis B virus DNA at the discretion of 
the Investigator. 
Unscheduled or additional laboratory tests with results reported by local laboratories may be 
performed if immediate results are necessary for management of treatment-emergent AEs or 
dosing determination. Unless otherwise noted, when scheduled simultaneously with a dosing 
visit, results of laboratory evaluations should be reviewed prior to administration of study drug.  
Detailed instructions for sample collection, processing, storage, and shipment will be provided in 
the Laboratory Manual. It is recommended that the smallest appropriate sampling tubes be used 
for local laboratory sample collection to curtail blood loss due to phlebotomy. 
7.2.8.1. 
Hematology 
Blood samples for hematology testing will be collected at timepoints detailed in the Schedule of 
Events (Appendix A and Appendix B). Hematology parameters shown in Table 8 will be 
analyzed according to standard methods at a local laboratory.  

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
60 
CONFIDENTIAL 
Subjects who discontinue study treatment for reasons other than PD will be contacted by 
telephone approximately every 90 days for 12 months after last study treatment for evidence of 
PD, collection of information about subsequent anti-tumor therapy, and assessment of survival 
status. Subjects who discontinue study treatment for PD will be contacted by telephone 
approximately every 90 days for 12 months after last study treatment for assessment of survival 
status. 
7.3. 
Pharmacokinetic Measurements 
Blood samples for assessment of plasma PK parameters for KZR-261 will be collected according 
to the Schedule of Events (Appendix A).  
7.4. 
Exploratory Assessments 
Samples for assessment of pharmacodynamic and other exploratory biomarkers will be collected 
during Cycles 1 and 2 from all subjects according to the Schedule of Events (Appendix A). 
7.4.1. 
Pharmacodynamic and Biomarker Measurements 
Whole blood samples will be collected for pharmacodynamic analyses according to the Schedule 
of Events (Appendix A and Appendix B). Pharmacodynamic analyses may include the 
monitoring of circulating proteins and/or proteins expressed in peripheral blood mononuclear 
cells. 
Whole blood and tumor biopsy samples will be collected according to the Schedule of Events 
(Appendix A and Appendix B) to study circulating and tumor-derived biomarkers of drug 
activity, such as can be found in the DNA, RNA, and protein components of these samples. 
RNA-based biomarkers of gene expression may be particularly relevant. Selection of the tumor 
types targeted for the expansion cohorts was guided, in part, by an analysis of gene modules 
(eg, modules encoding Sec61 clients, ribosomal proteins, and constituents of Golgi vesicles) 
whose expression is both associated with sensitivity to Sec61 inhibition in vitro and found to be 
frequently perturbed in the selected tumor types. Pre-treatment tumor biopsies will be evaluated 
for expression of these gene modules, and the results will be correlated with KZR-261 response 
in an exploratory fashion. In subjects for whom both an on-treatment and baseline sample are 
available, a paired analysis of changes in the expression of these modules will be performed to 
better understand KZR-261’s mechanism of action. 
Additional information regarding sample collection and handling will be outlined in the 
Laboratory Manual. 
7.5. 
Sample Management/Future Research 
All samples will be coded with the subject number. Samples and any data generated can be 
linked back to the subject as detailed in Section 4.1.1.  
Samples collected for future research may be retained by the Sponsor or its designate for up to 
5 years after study completion or as permitted by the applicable laws and regulations in the 
relevant country in which the study is conducted. Additional consent for storage of samples will 
be requested as a separate approval line on the ICF. Remaining de-identified unused clinical 
samples (blood/urine) will be retained by the Sponsor and used for the Sponsor’s future research, 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
61 
CONFIDENTIAL 
including, but not limited to, the evaluation of additional targets for novel therapeutic agents and 
to identify biomarkers for response and/or safety.  
If additional written consent is not provided, any remaining biological samples will be destroyed 
by the Sponsor or its designate following study completion.  

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
62 
CONFIDENTIAL 
8. 
STUDY DISCONTINUATION 
8.1. 
Stopping Rules for Safety 
8.1.1. 
Study Stopping Rules 
If any of the following events occur, the accumulated safety data will be reviewed by the SRC. 
• Death of any subject due to an AE, unless the Grade 5 event is a complication of 
disease progression or intercurrent illness. 
• Unexpected life-threatening event in 2 subjects, unless due to a complication of 
disease progression or intercurrent illness. 
• Any event that contraindicates further enrollment of additional subjects as assessed 
by either the SRC or a regulatory authority. 
In Part 2, the study will be halted if there is one Grade 5 or two Grade 4 AEs in different subjects 
considered at least possibly related to KZR-261. Exceptions include asymptomatic Grade 4 
laboratory abnormalities (eg, neutropenia) that resolve either with or without routine supportive 
care measures and without sequelae. 
Based on its review of any of the aforementioned scenarios, the SRC will have the ability to 
recommend the study be continued as is, continued with modification, or discontinued. 
Modifications could include implementation of additional monitoring measures or a reduction of 
KZR-261 dose. 
If any of these scenarios occurs, a formal safety analysis will be conducted, and the findings will 
be submitted to the IND for FDA review prior to enrolling additional subjects. 
8.1.2. 
Individual Subject Stopping Rules 
If any of the following events occur in an individual subject, administration of study drug should 
be held until a review of the accumulated safety data is undertaken by the Medical Monitor. 
• Any scenario that fulfills criteria for Study Stopping Rules (per Section 8.1.1). 
• Any scenario that, in the opinion of the Investigator or Medical Monitor 
contraindicates further dosing (eg, acute phase-like systemic drug reaction). 
After such a review, the Medical Monitor in conjunction with the Investigator may recommend 
the subject resume dosing, including consideration for any prophylactic interventions (as per 
Section 6.1.1), or discontinue dosing. Alternatively, the Medical Monitor may request that the 
SRC review all accumulated safety data prior to issuing a recommendation whether to resume or 
discontinue dosing.  
If any of the following events occur, administration of study drug to an individual subject should 
be discontinued: 
• Intolerable toxicity unresponsive to appropriate supportive interventions 
• Requirement for more than two dose reductions, or missed one entire treatment cycle 
• PD 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
63 
CONFIDENTIAL 
• Voluntary withdrawal by the subject from the study 
• Requirement for a prohibited medication without a suitable alternative (including 
non-protocol anticancer therapy) 
• DLT in Part 1, Cycle 1 
• Pregnancy 
• Physician’s decision 
• Closure of the study by the Sponsor (Section 8.3.2). 
Subjects discontinuing study treatment must complete EOT assessments, particularly safety 
evaluations. The primary reason for study treatment discontinuation will be identified and 
recorded on the appropriate eCRF, along with the date of discontinuation. 
8.2. 
Early Withdrawal of Subjects from Study 
In accordance with applicable regulations, a subject has the right to withdraw from the study, at 
any time and for any reason, without prejudice to future medical care. 
Subjects must be withdrawn from the study for any of the following reasons: 
• Subject request/withdraw consent for any reason 
Subjects may be withdrawn from the study for the occurrence of any of the following reasons: 
• Use of non-permitted concurrent therapy 
• Non-compliance with the study drug or study schedule 
• Lost to follow-up 
• Occurrence of AEs not compatible with the continuation of subject participation in 
the study, in the Investigator’s or Sponsor’s opinion, or unacceptable to the subject to 
continue 
• Investigator request 
• Sponsor request 
The reason(s) for study withdrawal, if available, will be documented in the eCRF. If a subject 
withdraws consent, all samples obtained will be retained for analysis unless the subject confirms 
in writing that he or she wishes the samples to be discarded. 
Reasonable efforts should be made to contact subjects who are lost to follow-up (defined as at 
least 3 unsuccessful contact attempts including 1 certified mail attempt). These efforts must be 
documented. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
64 
CONFIDENTIAL 
8.3. 
End of Treatment and End of Study 
8.3.1. 
End of Treatment (or Early Withdrawal) Visit 
The EOT / Early Withdrawal Visit will take place as soon as possible after permanent treatment 
discontinuation and prior to initiation of follow-on anticancer therapy (Appendix B). The 
following procedures will be performed at the EOT / Early Withdrawal Visit: 
• Record any AEs that have occurred since the last visit and any changes in 
concomitant medication 
• Record vital signs 
• Record any clinically significant changes from baseline in physical examination as 
AEs 
• Collect samples for hematology, clinical chemistry, and urinalysis. 
• Perform assessments of response, if the subject stops study treatment for reasons 
other than PD and the last response assessment was performed >4 weeks before the 
EOT visit.  
8.3.2. 
End of Study 
At End of Study (EOS) for each subject, disposition will be recorded. EOS will occur at the 
earliest of the following: 
• Long-term follow-up is complete 
• Voluntary withdrawal by the subject from the study 
• Subject death 
• Closure of the study by the Sponsor 
Completion of the conduct of the study is defined as the date of the last visit of the last subject. 
8.4. 
Study Termination 
The Sponsor has the right to terminate the study at any time if judged necessary for safety, 
regulatory, or other reasons consistent with applicable laws, regulations, and Good Clinical 
Practice (GCP). In this event, the Investigator(s) will be informed of the reason for study 
termination. Should this occur, all data available will also be recorded in the eCRFs. The 
Investigator should notify the relevant Institutional Review Boards (IRBs)/Independent Ethics 
Committees (IECs) in writing of the study’s completion or early discontinuation. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
65 
CONFIDENTIAL 
9. 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
9.1. 
Adverse Event Reporting 
9.1.1. 
Definitions 
An AE is defined as any untoward medical occurrence in a clinical study subject administered a 
medicinal product, which does not necessarily have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, disease, or medical condition temporally associated with the use of a 
medicinal (investigational) product, whether or not it is related to the medicinal (investigational) 
product. This includes an exacerbation of pre-existing conditions or events, intercurrent illnesses, 
or drug interaction. Anticipated fluctuations of pre-existing conditions, including the disease 
under study, that do not represent a clinically significant exacerbation or worsening need not be 
considered AEs. 
Progression of the underlying malignancy that is clearly consistent with the progression as 
defined by RECIST v1.1 criteria (or PCWG3 criteria in the setting of mCRPC), or other protocol 
defined criteria, is not considered an AE. Hospitalization due solely to progression of the 
underlying malignancy should not be reported as an SAE. 
If signs, symptoms and/or physical findings cannot be determined as exclusively due to 
progression of the underlying malignancy or do not fit the expected pattern of progression, these 
clinical symptoms should be reported as AEs or SAEs. 
If there is any uncertainty regarding an AE or SAE being due to progression of malignancy, 
these should be reported as AEs or SAEs.  
Signs and symptoms associated with overdose of KZR-261 must be reported as AEs. 
It is the responsibility of the Investigator to document all AEs that occur during the study. 
AEs will be elicited by asking the subject a nonleading question, for example, “Have you 
experienced any new or changed symptoms since we last asked/since your last visit?” 
AEs should be reported on the appropriate page of the eCRF. 
9.1.2. 
Assessment of Severity 
Severity of AEs will be graded according to NCI CTCAE v5.0. If there is a change in severity of 
an AE, it must be recorded as a separate event. For AEs not listed in the NCI CTCAE, the 
Investigator should determine the severity of the AE according to the criteria in Table 11. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
 
66 
CONFIDENTIAL 
Table 11: 
Adverse Event Severity Assessment 
Grade 1 (Mild) 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated.  
Grade 2 (Moderate) 
Moderate; minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living. 
Grade 3 (Severe) 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care activities of daily living. 
Grade 4 (Life-threatening) 
Life-threatening consequences; urgent intervention indicated. 
Grade 5 (Death) 
Death related to the adverse event. 
9.1.3. 
Assessment of Causality 
The Investigator will assess the causal relationship between study drug and an AE. AEs will be 
deemed related to study drug unless irrefutably determined to be related to the disease under 
study or another non-study drug cause.  
The causal relationship between the study drug and the AE will be assessed using 1 of the 
following 2 categories:  
Unrelated: An AE is not associated with study drug if any of the following is true:  
• A temporal relationship is lacking (ie, the event did not occur within a reasonable 
time frame after administration of the study drug) 
• Other causative factors more likely explain the event (eg, intercurrent illness, 
concomitant treatments, traumatic event).  
• The AE did not reoccur upon re-administration of the study drug (if applicable)  
Related: An AE is attributed to the study drug if any of the following is true:  
• There is a positive temporal relationship (ie, the event occurred within a reasonable 
time frame after administration of study drug)  
• The AE is more likely explained by the study drug than by another cause and cannot 
be clearly assessed as “unrelated” 
Reporting of unexpected adverse reactions is described in Section 9.5. 
9.1.4. 
Action Taken 
The Investigator will describe the action taken with study drug in the appropriate section of the 
eCRF, as follows: 
• None 
• Study drug stopped 
• Study drug temporarily interrupted 
• Study dose modification 
• Other, specify 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
67 
CONFIDENTIAL 
9.1.5. 
Follow-up of Adverse Events 
AEs are intended to be collected according to the procedures outlined above from the time of 
ICF and are to continue for 30 days following the last dose of study drug. 
All Investigators should follow up with subjects with AEs until the event is resolved or until, in 
the opinion of the Investigator, the event is stabilized or determined to be chronic. Details of AE 
resolution must be documented in the eCRF. 
9.1.6. 
Documentation and Reporting of Adverse Events 
AEs (including SAEs) should be reported and documented in accordance with the procedures 
outlined below. All AEs occurring during the study must be documented on the relevant eCRF 
pages. The following data should be documented for each AE: 
• Diagnosis or description of the symptom if diagnosis is not established 
• Classification of ‘serious’ or ‘not serious’ 
• Severity 
• Date of first occurrence and date of resolution (if applicable) 
• Action taken with study drug 
• Causal relationship with study drug 
• Whether medication or therapy was given 
• Outcome of event (unknown, recovered, not yet recovered, recovered with sequelae, 
death [with date and cause reported]) 
9.2. 
Serious Adverse Events 
9.2.1. 
Serious Adverse Events Definition 
An SAE is any untoward medical occurrence or affect that, at any dose: 
• Results in death 
• Is life-threatening (an AE is life-threatening if the subject was at immediate risk of 
death from the event as it occurred, ie, it does not include a reaction that might have 
caused death if it had occurred in a more serious form) 
• Requires or prolongs inpatient hospitalization. (Complications occurring during 
hospitalization are AEs and are SAEs if they cause prolongation of the current 
hospitalization. Hospitalization for elective treatment of a pre-existing non-worsening 
condition is not, however, considered an AE. The details of such hospitalizations 
must be recorded on the medical history or physical examination page of the eCRF) 
• Results in persistent or significant disability/incapacity. (An AE is incapacitating or 
disabling if it results in a substantial and/or permanent disruption of the subject’s 
ability to carry out normal life functions) 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
68 
CONFIDENTIAL 
• Results in a congenital anomaly/birth defect 
• Is an important medical event that requires medical and scientific judgement to decide 
if prompt notification is required in situations other than those defined for SAEs 
above. This may include any event that the Investigator regards as serious that did not 
strictly meet the criteria above but may have jeopardized the subject and may require 
medical or surgical intervention to prevent one of the other outcomes listed above. 
9.2.2. 
Serious Adverse Event Reporting and Documentation Requirements  
Any SAE must be reported as detailed in Section 9.1.6 by the Investigator if it occurs from the 
time of signed consent through 30 days after the last dose of study drug, whether or not the SAE 
is considered to be related to the investigational product. All Investigators should follow up with 
subjects with SAEs until the event is resolved or until, in the opinion of the Investigator, the 
event is stabilized or determined to be chronic. Details of SAE resolution must be documented. 
An SAE report consists of the SAE form, provided separately. If considered necessary, 
additional redacted source documents regarding an SAE may be requested.  
Redacted source documents (ie, medical records) should not be provided in lieu of a completed 
SAE report form. 
SAEs that occur during the reporting period must be reported by the Investigator to the 
 Safety Reporting e-mail address 
, or dedicated fax 
 (see also Study Personnel page at the front of this protocol) and entered 
into electronic data capture (EDC) within 24 hours from the point in time when the Investigator 
becomes aware of the SAE.  
The Investigator should not wait to receive additional information to fully document the event 
before notification of a SAE, though additional information may be requested. Where applicable, 
information from relevant laboratory results, hospital case records, and autopsy reports should be 
obtained. 
Instances of death, congenital abnormality, or an event that is of such clinical concern as to 
influence the overall assessment of safety, if brought to the attention of the Investigator at any 
time after cessation of study drug administration and considered by the Investigator to be related 
to participation in this study, should be reported to the study monitor. 
The Sponsor and/or the Contract Research Organization (CRO) will promptly notify all relevant 
Investigators and the regulatory authorities of findings that could adversely affect the safety of 
subjects, impact the conduct of the study or alter the IEC/IRB approval/favorable opinion of the 
study. In addition, the CRO and the Sponsor will expedite the reporting to all concerned 
Investigators, to the IECs/IRBs, where required, and to the regulatory authorities of all adverse 
reactions that are both serious and unexpected (Section 9.5.1). 
9.3. 
Pregnancy Reporting 
Pregnancy occurring in a subject or partner of a subject during a clinical investigation must be 
reported within 24 hours on a Pregnancy Monitoring Form. The outcome of a pregnancy should 
be followed up carefully and any abnormal outcome of the mother or the child should be 
reported. This also applies to pregnancies following the administration of the investigational 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
69 
CONFIDENTIAL 
product to the father prior to sexual intercourse. Infants should be followed for a minimum of 
8 weeks, and all findings should be reported to the Sponsor. Study drug is to be discontinued 
immediately upon Investigator knowledge of pregnancy in a subject.  
If the outcome of the pregnancy meets a criterion for immediate classification as an 
SAE-spontaneous abortion (any congenital anomaly detected in an aborted fetus is to be 
documented), stillbirth, neonatal death, or congenital anomaly–the Investigator should repeat the 
procedures for expedited reporting of SAEs (Section 9.2.2). 
Full details will be recorded on the withdrawal page of the eCRF, or an SAE report will be 
completed if the subject has completed the study. 
9.4. 
Adverse Events of Special Interest 
There are no identified AEs of special interest for this FIH study that require expedited reporting.  
9.5. 
Unexpected Adverse Reactions 
9.5.1. 
Unexpected Adverse Reaction Definition 
An unexpected adverse reaction is any untoward or unintended response that is related to the 
administration of the study drug at any dose that is not consistent with the applicable product 
information (eg, not listed in the Reference Safety Information section of the Investigator’s 
Brochure or prescribing information or not listed at the specificity or severity it has been 
observed). 
All suspected unexpected serious adverse reactions (SUSARs) will be subject to expedited 
reporting. The Sponsor and/or the CRO shall ensure that all relevant information about a SUSAR 
that is fatal or life-threatening is reported to the relevant competent authorities and IEC/IRB 
within 7 days after knowledge by the Sponsor of such a case and that relevant follow-up 
information is communicated within an additional 8 days. All other SUSARs will be reported to 
the relevant competent authorities and IEC/IRB within 15 days after knowledge by the Sponsor 
of such a case. Also, all Investigators that are involved in the current study and any study with 
KZR-261 will be informed regarding a SUSAR occurrence.  
All Investigators should follow up SUSARs until the event is resolved or until, in the opinion of 
the Investigator, the event is stabilized or determined to be chronic. Post-study SUSARs that 
occur after the subject has completed the clinical study must be reported by the Investigator to 
the Sponsor in the same manner. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
70 
CONFIDENTIAL 
10. 
STATISTICAL ANALYSES 
A detailed Statistical Analysis Plan will be prepared by the Sponsor and finalized prior to 
database lock. 
10.1. 
Sample Size Estimates 
10.1.1. 
Part 1 
The sample size for Part 1 will be approximately 70 subjects, but the actual sample size will 
depend on the number of dose levels of KZR-261, number of subjects per dose level, and the 
number of subjects treated at the MTD or the MAD(s) of KZR-261. 
Dose escalation will continue accruing until one of the three stopping conditions below is 
triggered: 
• The maximum sample size has been achieved, 
• MTD/MAD has been identified with sufficient accuracy: data from 6 to 
approximately 12 subjects have been accumulated at a dose that is deemed to be the 
MTD/MAD, or 
• All doses explored appear to be overly toxic and the MTD cannot be determined. 
Due to binomial data variability in small samples, DLTs may be observed in a first cohort(s) by 
chance even when the true probability (DLT) is fairly low. This could result in the estimated 
posterior DLT rate exceeding the targeted 30% very early in the trial, triggering an early stop 
when very few subjects (2-4) have been treated. To prevent stopping the trial prematurely in such 
cases, a step-down option with a lower dose of 0.9 mg/m2 is added to the dose grid. This dose 
will be explored only if a high DLT rate occurs in the first cohort assigned to 1.8 mg/m2, ie, it 
will not be used as a starting dose and the algorithm will always assign the first cohort of 
subjects to a dose of 1.8 mg/m2. 
10.1.2. 
Part 2A 
The sample size in Part 2A is based on clinical and statistical considerations. Upon identification 
of the MTD/MAD at the conclusion of Part 1, the study will continue with up to 4 tumor-specific 
expansion cohorts and 1 All-Tumors cohort in Part 2A. The tumor-specific cohorts (n = 15 at 
interim) may be increased up to 35 subjects per cohort to more precisely estimate the anti-tumor 
activity of KZR-261, if there is a sufficient efficacy signal at the interim analyses (Section 10.6) 
and if the tumor type is not selected for investigation in Part 2B (dose optimization). The All-
Tumors cohort may enroll up to 35 biopsy-evaluable subjects. 
10.1.3. 
Part 2B 
In Part 2B (Dose Optimization), up to 120 subjects (30 per each tumor-specific cohort [15 per 
dose level]) may be enrolled into up to 4 tumor-specific cohorts based on the totality of data after 
the MTD/MAD has been determined. The sample size for Part 2B is based on clinical 
considerations. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
71 
CONFIDENTIAL 
10.2. 
Analysis Populations 
Three (3) analysis populations are planned for the study as follows: 
• The Safety Population consists of all subjects who receive at least 1 dose of study 
treatment (KZR-261) and will be used for the safety analyses.  
• 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 using RECIST v1.1. 
• The PK Analysis Population consists of all subjects who receive at least 1 dose of 
KZR-261 and who have at least one post-dose PK sample with measurable 
concentration of KZR-261. Any protocol deviations affecting PK analyses may result 
in exclusion from summaries for individual time point concentrations, complete 
profiles, and/or PK parameters. These exclusions will be reviewed before database 
lock and confirmed with the Sponsor before implementation. 
Unless otherwise specified, all data will be summarized by dose level and overall for Part 1 
(Dose Escalation), tumor-specific cohort for Part 2A (Dose Expansion), and dose and tumor-
specific cohort for Part 2B (Dose Optimization). 
10.3. 
Demographics, Disposition, and Baseline Characteristics 
Subject enrollment and disposition, including reasons for early discontinuation from treatment 
and the study, will be summarized. 
Baseline demographic (including sex, age, race, ethnicity, weight, height, body mass index) and 
disease characteristics will be summarized. 
10.4. 
Methods of Analysis 
In general, descriptive statistics, including numbers and percentages for categorical variables and 
numbers, means, standard deviations, medians, minimums, and maximums for continuous 
variables will be provided. 
10.5. 
Statistical Analyses 
10.5.1. 
Dose Escalation Algorithm 
In Part 1, the dose escalation algorithm for the i3+3 design is rule-based and implemented by 
escalate (E), stay at the current dose (S) and de-escalate (D or DU), according to observed 
toxicities (Liu et al., 2020). Suppose dose d is the dose currently used to treat subjects, nd is the 
number of subjects who have been treated at dose d, and xd is the number of subjects who have 
experienced DLTs at dose d. The i3+3 design can be summarized as follows: at the current dose 
d, calculate two quantities xd / nd and (xd -1) / nd. The decision rules compare these two quantities 
to the equivalence interval (EI), and depending on the comparison outcome, decide the next dose 
level for enrolling subjects. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
72 
CONFIDENTIAL 
• If xd / nd is below the EI, escalate (E) and enroll subjects at the next higher dose 
(d + 1); 
− else, if xd / nd is inside the EI, stay (S) and continue to enroll subjects at the 
current dose d; 
− else, if xd / nd is above the EI, there are two scenarios: 
1. if (xd -1) / nd is below the EI, stay (S) and continue to enroll subjects at the 
current dose d, 
2. else, de-escalate (D or DU) and enroll subjects at a lower dose (d − 1). 
When d is the highest dose or the lowest dose, the above rules need to be modified as special 
cases. 
• If the current dose is the highest dose, and xd / nd is below the EI, stay (S) instead of 
escalate (E) and continue to enroll subjects at the current dose. This is because there 
is no dose to escalate to. 
• If the current dose is the lowest dose, and xd / nd is above the EI, stay (S) instead of 
potentially de-escalating (D or DU) and continue to enroll subjects at the current 
dose. This is because there is no dose to de-escalate to. 
Following the mTPI and mTPI-2 designs, two safety rules are added as ethical constraints to 
avoid excessive toxicity: 
• Safety rule 1 (early termination due to excessive toxicity at the lowest dose). In the 
special case of cohorts of size 1, this early stopping rule should not be applied until 
three or more patients have been evaluated at a dose.  
− The term, excessive toxicity at the lowest dose (dose 1) can be expressed 
mathematically as follows: assume n1 > 0, if Pr(p1 > pT | x1, n1) > ξ, for a 
large probability ξ, say 0.95 has occurred. Where Pr is probability and p1, pT, 
x1, and n1 represent “DLT rate at dose 1”, “target DLT rate”, “# of DLT at dose 1” 
and “cohort size at dose 1” respectively. 
• Safety rule 2 (dose exclusion): Suppose that the decision is to escalate from dose d to 
dose (d + 1). If there is a high probability that there is an excessive toxicity at dose 
(d + 1), ie, Pr( pd+1 > pT | xd+1, nd+1 ) > ξ for ξ = 0.95, then treat the next cohort of 
patients at dose d instead of (d + 1), and dose (d + 1) and higher doses will be 
removed from the trial. These doses will be marked as “DU” to indicate that they are 
Unacceptable to use in the trial anymore. 
Under the i3+3 design, a trial is terminated either when a prespecified sample size is reached or 
according to Safety rule 1. Table 1 provides a decision table in i3+3 design for up to 12 patients 
treated at a given dose with the targeted DLT rate 𝑝𝑇=0.3 and the equivalence interval 
(EI) = [0.25, 0.35].  
10.5.2. 
Estimation of MTD 
At the end of Part 1, the MTD selection under the i3+3 design follows the same procedure as in 
the mTPI and mTPI-2 designs (Liu et al., 2020). The MTD should be the dose that KZR-261’s 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
73 
CONFIDENTIAL 
DLT rate is closest to the prespecified target DLT rate and within the equivalence interval (EI); 
to select the dose as the estimated MTD with the smallest difference: |pˆ∗d −pT | among all the 
doses d for which nd > 0 and Pr(pd > pT |xd, nd) < ξ. Here pˆ∗d is the isotonically transformed 
posterior mean of pd, the same as that in the mTPI design (Zhou and Ji, 2020). If two or more 
doses tie for the smallest difference, perform the following rule. Let p∗ denote the 
transformed posterior mean pˆ∗d of the tied doses.  
• If p∗ < pT , choose the highest dose among the tied doses. 
• If p∗ > pT , choose the lowest dose among the tied doses. 
10.5.3. 
Simulations and Operating Characteristics of the i3+3 Design 
Other than the slightly different decision tables (see (Liu et al., 2020) [Figure A1 in Appendix 
D]), the i3+3, mTPI, and mTPI-2 designs use the same safety rules and same inference to select 
the MTD. Because the mTPI and mTPI-2 designs have been well established in the literature 
with desirable performance, as indicated by the authors (Liu et al., 2020), there is no need to 
conduct more and larger simulations, such as a simulation study with 1,000 random scenarios, to 
further evaluate the operating characteristics of the i3+3 design. The i3+3 design is expected to 
perform at a similar level as the mTPI and mTPI-2 designs due to its similar but slightly 
improved decision table, which puts i3+3 in par with other major model-based designs. 
10.5.4. 
Safety Analysis 
Safety analyses will be performed for all subjects who received at least 1 dose of study drug. 
Prior and concomitant medications will be coded using the WHO Drug dictionary (version 
March 2023 or later). Verbatim AE terms will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA) (version 26.0 or later). All AEs that occur after administration 
of the first dose of study drug and through 30 days after last dose of study drug will be 
considered treatment-emergent adverse events and will be summarized by MedDRA system 
organ class and preferred term. The incidences (percentages) of subjects experiencing each AE 
preferred term will be summarized. AEs will also be summarized by severity in accordance with 
NCI CTCAE v5.0 and by causality (relationship to study treatment). DLTs, AEs, Grade 3, Grade 
4, and Grade 5 AEs, SAEs, and AEs resulting in dose reductions, treatment interruptions, or 
treatment discontinuation will be summarized by MedDRA preferred terms. Deaths that occur 
after the first dose of study drug and through 30 days after the last dose of study drug will be 
considered “on treatment” deaths and will be summarized. All deaths will be listed.  
Clinical laboratory, vital sign measurements, and ECG data will be summarized descriptively 
(means, medians, standard deviations, and minimum and maximum values) by dose/treatment 
group and overall and at protocol-specified time points along with a summary of change from 
baseline at each protocol-specified time point.  
Incidences of clinical laboratory abnormalities will be summarized with descriptive statistics. 
Vital signs and physical examination results will be summarized with descriptive statistics. 
Changes from baseline in physical and ocular examination findings will be listed and described 
for each subject. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
 
74 
CONFIDENTIAL 
10.5.5. 
Anti-tumor Activity 
ORR is defined as the proportion of subjects achieving a best response of CR or PR according to 
RECIST v1.1. CBR is defined as the proportion of subjects achieving a best response of CR/PR 
or stable disease over a period of ≥2 consecutive response assessment time points. Subjects with 
mCRPC will be assessed for response/clinical benefit per PCWG3 guidelines. DOR is defined as 
the date from first occurrence of CR or PR to the date of documented PD or death. In assessing 
DOR, a subject alive and without disease progression will be censored at the date of the last 
evaluable disease assessment. PFS is defined as the date of initiation of study treatment to the 
date of documented PD or death from any cause, whichever occurs first. OS is defined as the 
date of initiation of study treatment to the date of death from any cause.  
The 2-sided exact CI using the Clopper-Pearson method will be calculated for response/clinical 
benefit rates where applicable (Clopper and Pearson, 1934). Distributions for PFS, DOR, and OS 
will be estimated by Kaplan-Meier methodology. 
The CBR will be summarized by response assessment timepoints (ie, every 2 cycles). 
Summary tables of best ORR, PFS, and OS will be provided overall and by malignancy if 
necessary. Efficacy listings will be provided that include best response, first CR/PR date, last 
date with CR or PR, most recent date without progression, progression date, death date, and last 
tumor assessment date, etc. The definition of each response category is provided in RECIST 
v1.1. 
Table 12 provides an overview of the planned efficacy analysis. 
Table 12: 
Anti-tumor Assessments 
Endpoint 
Analysis Sets 
Statistical Method  
Objective response rate (ORR) 
Dose Expansion and Optimization 
cohorts 
Exact CI 
Progression-free survival (PFS) 
 Dose Expansion and Optimization 
cohorts 
Kaplan-Meier 
 
 
 
Duration of response (DOR) 
 Dose Expansion and Optimization 
cohorts 
Kaplan-Meier 
Overall survival (OS) 
 Dose Expansion and Optimization 
cohorts 
Kaplan-Meier 
Clinical benefit rate (CBR) 
 Dose Expansion and Optimization 
cohorts 
Exact CI 
CI=confidence interval. 
Note: Anti-tumor analyses may include patients in dose escalation phase. 
10.5.6. 
Pharmacokinetics 
PK parameters will be calculated from measurements of KZR-261 plasma concentrations at 
prespecified timepoints pre- and post-infusion using noncompartmental methods. Other 
approaches, such as population PK analyses may be considered, if appropriate. PK parameters to 
be calculated (if adequate data are available for estimation) will include, but not be limited to, 
Cmax, AUC, t½, CL, and Vz. Concentrations and PK parameters of KZR-261 will be summarized 
for each dose level by cycle and day in Part 1 using descriptive statistics. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
 
75 
CONFIDENTIAL 
10.5.7. 
Exploratory Assessments 
Assessments of various pharmacodynamic study readouts as a function of dose and time 
post-administration will be described and related to anticancer activity, PK, and safety 
parameters (Section 7.4.1). 
10.5.8. 
Handling of Missing Data 
Subjects discontinue study treatment and/or the study for any reason will be included in all 
analyses regardless of the duration of treatment. There will be no imputation for missing data, 
unless otherwise specified in the Statistical Analysis Plan. 
10.6. 
Interim Analyses 
The Go/No-Go futility analysis for each tumor-specific cohort in Part 2A will be based on CBR 
as the primary outcome measurement (as defined in Section 10.5.5) after Stage 1 enrollment of 
15 subjects. Each of the expansion cohorts is based on the following assumptions: 
• Each expansion cohort has a maximum sample size of 35 with one interim futility 
analysis at 15 subjects. At the interim analysis, if there is 1 or no subject with CBR 
(ie, CBR rate <7%), further enrollment into the cohort will be stopped for futility. If 
futility is rejected at the interim analysis (ie, 2 or more of 15 subjects with clinical 
benefit), the final analysis will be based on a total 35 subjects (ie, 20 additional 
subjects evaluable for CBR). Note: Outcomes (ie, presence or absence of clinical 
benefit) for subjects enrolled in Part 1 with the same tumor type and who received the 
same dose of KZR-261 as evaluated in the corresponding Part 2A, tumor-specific 
cohort may be included among the initial 15 subjects at the interim analysis, as 
described above. 
The operating characteristics of this design are presented in Table 13. If the true CBR is less than 
5%, there is a reasonable chance to reach the futility criterion at interim. On the other hand, if the 
true CBR is 20% or higher, the probability to stop for futility is moderately low (<20%). 
Table 13: Operating Characteristics of Dose Expansion Phase (Part 2A) 
True CBR 
Interim Analysis 
(N=15) 
Final Analysis 
(N=35) 
Pr(Futility*) 
Pr(obs. CBR ≥15% 6 or 
more subjects with CBR) 
Pr(obs. CBR ≥20% 7 or 
more subjects with CBR) 
Pr(obs. CBR ≥25% 9 or 
more subjects with CBR) 
5% 
83% 
<1% 
<1% 
<1% 
10% 
55% 
11% 
5% 
<1% 
15% 
32% 
39% 
25% 
7% 
20% 
17% 
67% 
54% 
25% 
25% 
8% 
86% 
78% 
52% 
30% 
4% 
95% 
92% 
76% 
35% 
1% 
98% 
97% 
91% 
CBR=clinical benefit rate; obs.=observed; Pr=probability 
* 1 or fewer subjects with CBR among the first 15 subjects. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
76 
CONFIDENTIAL 
11. 
ETHICAL AND ADMINISTRATIVE CONSIDERATIONS 
11.1. 
Compliance Statement 
The Investigator(s) and all parties involved in this study should conduct the study in adherence to 
the ethical principles based on the Declaration of Helsinki, International Council for 
Harmonisation (ICH) guidelines for current GCP, and the applicable national and local laws and 
regulatory requirements. 
Relevant study documentation will be submitted to the regulatory authorities of the participating 
countries, according to local/national requirements, for review and approval before the beginning 
of the study. On completion of the study, the regulatory authorities will be notified that the study 
has ended. 
11.2. 
Institutional Review Board or Independent Ethics Committee 
Before initiation of the study at each study center, the protocol, the ICF, other written material 
given to the subjects, and any other relevant study documentation will be submitted to the 
appropriate IEC/IRB. Written approval of the study and all relevant study information must be 
obtained before the study center can be initiated or the study drug is released to the Investigator. 
Any necessary extensions or renewals of IEC/IRB approval must be obtained for changes to the 
study (ie, amendments to the protocol, the ICF, or other study documentation). The written 
approval of the IEC/IRB together with the approved ICF must be filed in the study files. 
The Investigator will promptly report to the IEC/IRB any new information that may adversely 
affect the safety of the subjects or the conduct of the study. The Investigator will submit written 
summaries of the study status to the IEC/IRB as required. On completion of the study, the 
IEC/IRB will be notified that the study has ended. 
11.3. 
Informed Consent and Human Subject Protection 
The process of obtaining informed consent must be in accordance with applicable regulatory 
requirement(s) and must adhere to current GCPs. 
Subjects will provide written informed consent before any study-related procedures are 
performed unless the procedure or assessment is consistent with the standard of care for the 
underlying malignancy. 
The Investigator is responsible for ensuring that no subject undergoes any study-related 
examination or activity before that subject has given written informed consent to participate in 
the study unless the procedure or assessment is consistent with the standard of care for the 
underlying malignancy. 
The Investigator or designated personnel will inform the subject of the objectives, methods, 
anticipated benefits, potential risks, and inconveniences of the study. The subject should be given 
every opportunity to ask for clarification of any points s/he does not understand and, if 
necessary, ask for more information. At the end of the interview, the subject will be given ample 
time to consider the study. Subjects will be required to sign and date the ICF. After signatures 
are obtained, the ICF will be kept and archived by the Investigator in the Investigator’s study 
file. A signed and dated copy of the subject ICF will be provided to the subject. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
77 
CONFIDENTIAL 
It should be emphasized that the subject may refuse to enter the study or to withdraw from the 
study at any time, without consequences for their further care or penalty or loss of benefits to 
which the subject is otherwise entitled. Subjects who refuse to give or who withdraw written 
informed consent should not be included or continue in the study. 
If new information becomes available that may be relevant to the subject’s willingness to 
continue participation in the study, a new ICF will be approved by the IEC(s)/IRB(s) (and 
regulatory authorities, if required). The study subjects will be informed about this new 
information and reconsent will be obtained. 
11.4. 
Direct Access to Source Data, Source Documents, and Study Records 
The Sponsor or its representatives may periodically check a sample of the subject data recorded 
against source documents at the study site. The study may be audited by the Sponsor and/or 
regulatory agencies at any time. Investigators will be given notice before an audit occurs. 
The Investigator will keep records of all original source data. This might include laboratory tests, 
medical records, and clinical notes. If requested, the Investigator will provide the Sponsor, 
applicable regulatory agencies, and applicable review boards with direct access to the original 
source documents. 
11.5. 
Data Collection and Handling 
An EDC system will be used in this study. The study site must define and retain all source 
records and must maintain a record of any data where source data are directly entered into the 
data capture system.  
Data systems used for the study will have controls and requirements in accordance with local 
data protection law.  
The purpose and use of subject personal information collected will be provided in a written 
document to the subject by the Sponsor. 
11.6. 
Confidentiality 
Monitors, auditors, and other authorized agents of the Sponsor and/or its designate, the 
IEC(s)/IRB(s) approving this research, and the FDA, as well as that of any other applicable 
agency(ies), will be granted direct access to the study subjects’ original medical records for 
verification of clinical study procedures and/or data, without violating the confidentiality of the 
subjects to the extent permitted by the law and regulations. In any presentations of the results of 
this study or in publications, the subjects’ identity will remain confidential. 
All personal data collected and processed for the purposes of this study should be managed by 
the Investigator and his/her staff with adequate precautions to ensure confidentiality of those 
data, and in accordance with the Health Insurance Portability and Accountability Act, applicable 
to national and/or local laws and regulations on personal data protection. 
11.7. 
Financing and Insurance 
Financing and insurance of this study will be outlined in a separate agreement between the CRO 
and the Sponsor. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
78 
CONFIDENTIAL 
11.8. 
Audit and Inspection 
Study centers and study documentation may be subject to Quality Assurance audit during the 
course of the study by the Sponsor or its nominated representative. In addition, inspections may 
be conducted by regulatory authorities at their discretion. 
11.9. 
Monitoring 
Data for each subject will be recorded on an eCRF. Data collection must be completed for each 
subject who signs an ICF. 
In accordance with current GCP and ICH guidelines, the study monitor will carry out source 
document verification at regular intervals to ensure that the data collected in the eCRF are 
accurate and reliable.  
The Investigator must permit the monitor, the IEC/IRB, the Sponsor’s internal auditors, and 
representatives from regulatory authorities’ direct access to all study-related documents and 
pertinent hospital or medical records for confirmation of data contained within the eCRFs.  
11.10. 
Quality Control and Quality Assurance 
All aspects of the study will be carefully monitored by the Sponsor or its authorized 
representative(s) for compliance with applicable government regulations with respect to current 
GCP and Standard Operating Procedures. 
11.11. 
Data Management and Coding 
The Sponsor or the CRO will be responsible for activities associated with the data management 
of this study. This will include setting up a relevant database and data transfer mechanisms, 
along with appropriate validation of data and resolution of queries. Data generated within this 
clinical study will be handled according to the relevant standard operating procedures of the data 
management and biostatistics departments of Sponsor or the CRO. 
Study centers will enter data directly into an EDC system by completing the eCRF via a secure 
internet connection. Data entered into the eCRF must be verifiable against source documents at 
the study center. Data to be recorded directly on the eCRF will be identified and the eCRF will 
be considered the source document. Any changes to the data entered into the EDC system will be 
recorded in the audit trail and will be FDA CFR 21 Part 11 compliant. 
Medical coding will use MedDRA for concomitant diseases and AEs with World Health 
Organization drug classifications being used for medications. 
Missing or inconsistent data will be queried in writing to the Investigator for clarification. 
Subsequent modifications to the database will be documented.  
11.12. 
Reporting and Publication, Including Archiving 
Essential documents are those documents that individually and collectively permit evaluation of 
the study and quality of the data produced. After completion of the study (end of study defined as 
the date of the last visit of the last subject), all documents and data relating to the study will be 
kept in an orderly manner by the Investigator in a secure study file. This file will be available for 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
79 
CONFIDENTIAL 
inspection by the Sponsor or its representatives. Essential documents should be retained for 
2 years after the final marketing approval in a region, for at least 2 years since the 
discontinuation of clinical development of the investigational product, or according to local 
requirements, whichever is longer. It is the responsibility of the Sponsor to inform the study 
center when these documents no longer need to be retained. The Investigator must contact the 
Sponsor before destroying any study-related documentation. In addition, all subject medical 
records and other source documentation will be kept for the maximum time permitted by the 
hospital, institution, or medical practice. 
The Sponsor must review and approve any results of the study or abstracts for professional 
meetings prepared by the Investigator(s). Published data must not compromise the objectives of 
the study. Data from individual study centers in multicenter studies must not be published 
separately. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
81 
CONFIDENTIAL 
13. 
APPENDICES

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
84 
CONFIDENTIAL 
e 
When performed at the same time point, vital sign measurements should be performed per institutional guidelines, preferably prior to ECGs. A 12-lead ECG 
is performed 10 minutes after the subject has been in the supine position. ECGs will be performed on Days 1 and 15 of Cycles 1 and 2 pre-treatment, 15 
minutes after the start of the infusion, at the end of the infusion, and 5 and 30 minutes, and 2, 4, 6, and 24 hours (Day 2 and Day 16) post-infusion. 
Additional ECGs will be performed on Day 8, 30 minutes prior to infusion, and 5 and 15 minutes and 1-hour post-infusion. ECG time points during the 
infusion, at the end of the infusion, and ≤1 hour post-infusion have a ±2 minute window. ECG time points >1 hour post-infusion have a ±5 minute window; 
the 24-hour ECG has a ±60 minute window. 
f 
Tumor biopsies (fresh [preferred] or archived) will be requested pre-treatment. Although a fresh sample is preferred, submission of an adequate tumor 
specimen (paraffin block) collected within one year before the subject’s first dose of KZR-261 will be acceptable for subjects where a fresh sample cannot 
be obtained. If a paraffin block is not available, a minimum of 10 and up to 20 5-µm unstained slides should be provided. For any subject who provided a 
tumor sample pre-treatment, an additional biopsy of accessible tumor will be requested at either the end of Cycle 2 (Days 21-28 of Cycle 2) or at PD, 
whichever comes first.  
Pre-treatment tumor biopsies (fresh only) will be required for subjects enrolled in the All-Tumors expansion cohort (exceptions to this requirement may be 
considered after discussion with the Medical Monitor); an additional biopsy of accessible tumor tissue will be required at either the end of Cycle 2 (Days 21-
28 of Cycle 2) or at PD, whichever comes first. Blood samples for coagulation parameter tests must be collected within 24 hours prior to all biopsy 
procedures. 
g 
Blood samples for serum chemistry tests must be collected with subject in a fasting state (ie, no food or caloric drinks for at least 6 hours before testing, or 
overnight). For coagulation parameter tests, either PT or INR may be measured, and either PTT or aPTT, depending on institutional standards. Blood 
samples for coagulation parameter tests must be collected within 24 hours prior to all biopsy procedures. It is recommended that the smallest appropriate 
sampling tubes be used for sample collection to curtail blood loss due to phlebotomy. 
h 
Urinalysis dipstick testing is acceptable. 
i 
Only subjects with mCRPC. 
j 
If tumor markers in blood (eg, PSA, CA-125, CEA, CA-15.3, CA-19.9) are known to be elevated, they should be measured. 
k 
All subjects must have Baseline imaging (CT scan of chest/abdomen/pelvis or MRI, as indicated) within 28 days prior to first dose of study treatment. 
Imaging should be repeated prior to Cycle 3 (ie, end of Cycle 2) There is a 7-day window around imaging procedures to allow time for result availability 
prior to the next cycle. If an imaging procedure must be scheduled to occur outside the 7-day window allowance, this should be discussed with the Medical 
Monitor for approval prior to the procedure. Response assessments will be conducted in accordance with RECIST 1.1 criteria. Subjects with mCRPC will be 
assessed per PCWG3 guidelines. All subjects with mCRPC will have bone scans at the same time points as the imaging procedures. Subjects with skin, 
subcutaneous, or lymph node metastases may also have tumor evaluations (including measurements, with a ruler or calipers) by means of physical 
examination. 
l 
Plasma PK samples will be collected during Part 1 on Days 1 and 15 of Cycles 1 and 2 pre-treatment, 15 minutes post-start of infusion, end of infusion, 5 
minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 24 hours (ie, Day 2 and Day 16) post-infusion. An additional plasma sample will be 
obtained in Cycles 1 and 2 at 48 hours (Day 3) and 96 hours (Day 5) post-infusion and on Day 8 at pre-treatment (30 minutes prior to infusion), 15 minutes 
and 1 hour after  completion of the infusion. 
Plasma PK samples will be collected during Parts 2A and 2B on Day 1 of Cycle 1 at the end of infusion and 24 hours post-start of infusion (Day 2). An 
additional plasma sample will be obtained on Days 8 and 15 prior to infusion and Day 15 at the end of infusion. 
Windows for PK sampling are provided in the laboratory manual.  
m 
Whole blood samples will be collected for pharmacodynamic studies Cycle 1 Day 1 pre-treatment, 6 hours post-dose, 24 hours post-dose (Day 2), Cycle 1 
Day 8 pre-treatment and Cycle 1 Day 15 pre-treatment, 6 hours post-dose, 24 hours post-dose (Day 16), and Cycle 2 Day 1 pre-treatment in a 
 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
85 
CONFIDENTIAL 
tube for RNAseq, in sodium heparin to be shipped to central laboratory for PBMC processing, and in sodium heparin processed onsite to plasma samples (as 
described in the laboratory manual). Samples will be collected on Cycle 1 Day 28 if treatment is halted and not proceeding to Cycle 2. 
n 
Whole blood will be collected in a 
 tube and shipped to the central laboratory for processing to plasma samples (for circulating tumor DNA 
testing) and cell pellet (cellular genomic DNA) pre-treatment Day 1 of Cycle 1, pre-treatment Day 1 Cycle 2, or at time of disease progression. 
o 
Subjects should remain at the study site for 6 hours following study treatment administration for observation for the first cycle, first dose (Cycle 1 Day 1) 
and for 2 hours for the rest of Cycle 1 dosing (Cycle 1 Days 8 and 15). For Cycle 2, subjects will be under observation for 1 hour following study treatment 
administration. For Cycle 3 and beyond, there will be no required monitoring following study treatment administration. 
p 
Day 28 assessments of the prior cycle may be combined with Day 1 of the next cycle. Whenever possible, these evaluations should be referred to as the End 
of Cycle evaluation (for the earlier cycle) as opposed to the beginning of cycle evaluation for the subsequent cycle. 
q 
For subjects who discontinue study treatment during or after Cycles 1 or 2, see EOT evaluations in Appendix B. Subsequent to discontinuation of study 
treatment, subjects will have an EOT visit as soon as possible following their last KZR-261 dose and prior to initiation of follow-on anticancer therapy. 
Safety follow-up by telephone will occur approximately 30 days following their last KZR-261 dose. Subjects who discontinue study treatment for reasons 
other than PD will be contacted by telephone approximately every 90 days for 12 months after last study treatment for evidence of PD, collection of 
information about subsequent anti-tumor therapy, and assessment of survival status. Subjects who discontinue study treatment for PD will be contacted by 
telephone approximately every 90 days for 12 months after last study treatment for assessment of survival status. 
r 
HgbA1c to be measured at pre-treatment (baseline). 
s 
Subjects will have monitoring for cataracts at Screening, at the end of Cycle 1 prior to the start of Cycle 2, and at the end of Cycle 2 prior to Cycle 3. 
t 
Day 3 and Day 5 visits are for Part 1 only. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
87 
CONFIDENTIAL 
PSA=prostate-specific antigen; PT=prothrombin time; PTT=partial thromboplastin time; RECIST=Response Evaluation Criteria in Solid Tumors; SAE=serious 
adverse event; WOCBP=woman of childbearing potential 
a 
For Cycles 3+, an abbreviated physical examination including weight, is only required prior to the start of each cycle (Day 1) and at the EOT visit. Subjects 
with skin, subcutaneous, or lymph node metastases may also have tumor evaluations (including measurements, with a ruler or calipers) by means of physical 
examination. Patients will be asked at each visit about mouth dryness and salivary gland pain and sensitivity, and urinary and ejaculation issues. 
b 
Subjects will have monitoring for cataracts at Cycle 4 Day 1 ±3 days, Cycle 6 Day 1 ±3 days. Slit lamp and visual acuity examinations should be conducted 
at EOT. 
c 
For WOCBP, a negative serum or urine pregnancy test, whichever is preferred, is required at all visits indicated. A positive urine pregnancy test result 
should be confirmed by a serum pregnancy test. Pregnancy testing may occur more frequently if required by local/institutional regulations. 
d 
Vital signs and oxygen saturation will be measured at all visits. Blood pressure and pulse should be measured after the subject has had at least 5 minutes of 
rest in the seated position. If blood pressure is elevated on the first measurement at Screening or Baseline, it should be repeated after an additional 5 minutes 
of rest. It is recommended that blood pressure be obtained from the same arm at each assessment. 
e 
When performed at the same time point, vital sign measurements should be performed per institutional guidelines, preferably prior to ECGs. A 12-lead ECG 
is performed 10 minutes after the subject has been in the supine position. ECGs will be performed on Day 1 pre-treatment and at the end of infusion for all 
cycles. For Cycle 4 only, ECGs will be performed on Days 1 and 15 at pre-treatment, 15 minutes after the start of the infusion, at the end of the infusion, and 
5 and 30 minutes, and 2, 4, and 6 hours post-infusion. Additional ECGs for Cycle 4 only will be performed on Day 8, 30 minutes prior to infusion, and 5 and 
15 minutes and 1 hour post-infusion. ECG time points during the infusion, at the end of the infusion, and ≤1 hour post-infusion have a ±2 minute window. 
ECG time points >1 hour post-infusion have a ±5 minute window. ECG time points >1 hour post-infusion have a ±5 minute window. 
f 
Blood samples for serum chemistry tests must be collected with subject in a fasting state (ie, no food or caloric drinks for at least 6 hours before testing, or 
overnight). For coagulation parameter tests, either PT or INR may be measured, and either PTT or aPTT, depending on institutional standards. It is 
recommended that the smallest appropriate sampling tubes be used for sample collection to curtail blood loss due to phlebotomy. 
g 
Urinalysis dipstick testing is acceptable. 
h 
Only subjects with mCRPC. 
i 
If tumor markers in blood (eg, PSA, CA-125, CEA, CA-15.3, CA-19.9) are known to be elevated, they should be measured. 
j 
Imaging should be repeated prior to Cycle 3, prior to Cycle 5 (ie, end of Cycle 4) and every 2 cycles thereafter (ie, end of Cycles 4, 6, 8 etc.). There is a 
7-day window around imaging procedures to allow time for result availability prior to the next cycle. If an imaging procedure must be scheduled to occur 
outside the 7-day window allowance, this should be discussed with the Medical Monitor for approval prior to the procedure. Imaging should be repeated at 
EOT if the last response assessment was >4 weeks prior. Tumors will be measured according to RECIST v1.1. Subjects with mCRPC will be assessed per 
PCWG3 guidelines. All subjects with mCRPC will have bone scans at the same time points as the imaging procedures. Subjects with skin, subcutaneous, or 
lymph node metastases may also have tumor evaluations (including measurements, with a ruler or calipers) by means of physical examination. 
k 
Day 28 assessments of the prior cycle may be combined with Day 1 of the next cycle. Whenever possible, these evaluations should be referred to as the End 
of Cycle evaluation (for the earlier cycle) as opposed to the beginning of cycle evaluation for the subsequent cycle. 
l 
Subsequent to discontinuation of study treatment, subjects will have an EOT visit as soon as possible following their last KZR-261 dose and prior to 
initiation of follow-on anticancer therapy. Safety follow-up by telephone will occur approximately 30 days after the subject’s last dose of study treatment. If 
AEs have not resolved at that time, additional safety follow-ups will occur approximately every 30 days until AE resolution or until, in the opinion of the 
Investigator, the event is stabilized or determined to be chronic.  
If a subject attending a Day 28 or Day 1 visit meets criteria for EOT, the EOT visit assessments should be conducted instead of Day 28/Day 1 assessments. 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
88 
CONFIDENTIAL 
m 
Subjects who discontinue study treatment for reasons other than PD will be contacted by telephone approximately every 90 days for 12 months after last 
study treatment for evidence of PD, collection of information about subsequent anti-tumor therapy, and assessment of survival status. Subjects who 
discontinue study treatment for PD will be contacted by telephone approximately every 90 days for 12 months after last study treatment for assessment of 
survival status.  
n 
Whole blood will be collected in a
 tube and shipped to the central laboratory for processing to plasma samples (for circulating tumor DNA 
testing) and cell pellet (cellular genomic DNA) pre-treatment Day 1 of Cycles 3-6. A circulating tumor DNA sample should be collected at EOT or at time 
of disease progression. This collection is not required for subjects who continue to receive treatment beyond Cycle 6. 
o 
HgbA1c to be measured on Day 28 every 3 cycles (ie, end of Cycles 3, 6, 9, etc.) or at Day 1 prior to treatment of the following cycles (ie, Day 1 of cycles 4, 
7, 10, etc.). 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
89 
CONFIDENTIAL 
APPENDIX C. LIST OF PREFERRED TUMORS FOR THE ALL-
TUMORS COHORT 
Based on the bioinformatics study (Section 1.2.1) and the evaluation of KZR-261 in tumor 
xenograft models, the following tumor types are prioritized for inclusion in the All-Tumors 
cohort: 
• 
Urothelial carcinoma 
• 
Soft tissue sarcoma (except GIST) 
• 
Head and neck carcinoma 
• 
Small-cell lung cancer 
• 
Hepatocellular carcinoma 
• 
Pancreatic cancer 

Protocol, Version 5.0 
Kezar Life Sciences 
KZR-261-101 
02 October 2023 
90 
CONFIDENTIAL 
APPENDIX D. LIST OF SENSITIVE SUBSTRATES OF CYP3A4 
The list below is available at https://www.fda.gov/drugs/drug-interactions-labeling/drug-
development-and-drug-interactions-table-substrates-inhibitors-and-inducers. See also 
https://drug-interactions.medicine.iu.edu/MainTable.aspx.  
Note: This list contains examples and is not intended to be exhaustive. 
Category 
Drug Names 
Sensitive substrates of CYP3A 
alfentanil, avanafil, buspirone, conivaptan, darifenacin, 
darunavir, ebastine, everolimus, ibrutinib, lomitapide, lovastatin, 
midazolam, naloxegol, nisoldipine, saquinavir, simvastatin, 
sirolimus, tacrolimus, tipranavir, triazolam, vardenafil 
 
budesonide, dasatinib, dronedarone, eletriptan, eplerenone, 
felodipine, indinavir, lurasidone, maraviroc, quetiapine, 
sildenafil, ticagrelor, tolvaptan