KZR-261 / Kezar - LARVOL DELTA

KZR-261 in Subjects With Advanced Solid Malignancies (clinicaltrials.gov) - P1 | N=61 | Active, not recruiting | Sponsor: Kezar Life Sciences, Inc. | Recruiting ➔ Active, not recruiting | N=225 ➔ 61

Enrollment change • Enrollment closed • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Prostate Cancer • Solid Tumor

Kezar Life Sciences Reports Second Quarter 2024 Financial Results and Provides Business Update (Businesswire) - P1 | N=225 | NCT05047536 | Sponsor: Kezar Life Sciences, Inc. | "Enrollment has been stopped in the KZR-261 Phase 1 study, and clinical resources are being reallocated toward development of zetomipzomib....Patients already enrolled in the study will continue to have access to KZR-261. A total of 61 patients enrolled across the dose-escalation and dose expansion portions of the study, which included seven patients enrolled in the melanoma cohort of the dose-expansion portion at a dose level of 60 mg/m2. No objective responses have been observed to date in the study. Five patients (two with melanoma) within the dose escalation portion of the study experienced stable disease for four months or longer, of which two patients (melanoma; head and neck) experienced stable disease for twelve months or longer. KZR-261 has demonstrated consistent pharmacokinetics across all dose levels....Kezar plans to report full data at a medical conference following completion of the study."

P1 data • Trial termination • Head and Neck Cancer • Melanoma

Kezar Life Sciences Reports First Quarter 2024 Financial Results and Provides Business Update (Businesswire) - P1 | N=225 | NCT05047536 | Sponsor: Kezar Life Sciences, Inc. | "KZR-261-101: We are currently enrolling the dose expansion part of the study with a cohort of melanoma patients at a dose level of 60 mg/m2. To date, KZR-261 has shown dose-proportional exposure and no signs of accumulation or altered pharmacokinetics with repeated dosing."

P1 data • Trial status • Melanoma

Kezar Life Sciences Reports Fourth Quarter and Year End 2023 Financial Results and Provides Business Update (Businesswire) - "The KZR-261 trial is currently enrolling Cohort 9 (80 mg/m2). Previously, Cohort 1 (1.8 mg/m2) through Cohort 8 (60 mg/m2) enrolled a total of 35 patients and completed rapid dose escalation without significant safety concerns."

Trial status • Solid Tumor

Quantitative proteomic profiling of KZR-540, a novel small molecule oral Sec61 inhibitor that selectively inhibits PD-1 expression (SITC 2023) - P1 | "1 Here we utilized LC/MS-based quantitative proteomic profiling to study the unique selectivity of KZR-540 in contrast to the promiscuous Sec61 inhibitor KZR-261 and its analog KZR-834. KZR-261 is currently being evaluated in a phase-1 clinical trial in solid tumors (NCT05047536). Follow-up in vivo studies will examine the differential impact of KZR-540 and KZR-261/834 on the tumor-draining lymph nodes (TDLNs) and plasma proteomes of human-PD-1 knock-in mice bearing human-PD-L1 MC38 tumors."

IO biomarker • Oncology • Solid Tumor • PD-L1 • SEC61G

Kezar Life Sciences Announces Strategic Restructuring to Prioritize Clinical-Stage Assets and Extend Financial Runway and Appoints Christopher Kirk, Ph.D. as Chief Executive Officer (Businesswire) - "Kezar anticipates initial data from its KZR-261 Phase 1 clinical trial in 2024....Kezar is also evaluating its Phase 1 clinical trial of KZR-261 in solid tumors and expects to reduce the number of planned expansion cohorts to conserve cash resources while it continues to evaluate safety and biologic activity in the ongoing trial."

Clinical protocol • P1 data • Solid Tumor

KZR-261 in Subjects With Advanced Solid Malignancies (clinicaltrials.gov) - P1 | N=225 | Recruiting | Sponsor: Kezar Life Sciences, Inc. | Trial completion date: Oct 2023 ➔ Dec 2026 | Trial primary completion date: Aug 2023 ➔ Dec 2025

Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Melanoma • Oncology • Prostate Cancer • Solid Tumor

KZR-261 in Subjects With Advanced Solid Malignancies (clinicaltrials.gov) - P1; N=225; Recruiting; Sponsor: Kezar Life Sciences, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Melanoma • Oncology • Solid Tumor

Kezar Life Sciences Reports Fourth Quarter and Year End 2022 Financial Results and Provides Business Update (Businesswire) - "KZR-261 has shown dose-proportional exposure and no signs of accumulation or altered pharmacokinetics with repeated dosing. There have been no consistent patterns of safety signals. Kezar plans to report safety and dose escalation data from this trial in the second half of 2023."

P1 data • Oncology • Solid Tumor

KZR-540 is a novel oral small molecule inhibitor of Sec61 cotranslational translocation that potently and selectively blocks PD-1 expression (SITC 2022) - P1 | "Targeting Sec61 with small molecule inhibitors such as KZR-261, currently in a clinical trial for solid tumors ( NCT05047536 ), has anti-tumor effects through inhibiting the expression of multiple therapeutic targets, including PD-1, in preclinical models. Future studies will examine whether there is an enhanced anti-tumor response in a tumor model. Ethics Approval Animal studies were approved by the Institutional Animal Use and Care Committee."

IO biomarker • Melanoma • Oncology • Solid Tumor • IFNG • SEC61G

Sec61 inhibitor KZR-834, an anti-cancer agent, exhibits immunomodulatory activity and combines with PD-1 blockade to further enhance immune responses (AACR 2022) - P1 | "KZR-261 is a first-in-class small molecule Sec61 inhibitor currently in a Phase I clinical trial in patients with advanced solid tumors (NCT05047536). Specifically, in the MC38 tumor model, KZR-834 combines with anti-PD-1 antibody to enhance immune responses. These data support further investigation into combining KZR-834 with immune checkpoint inhibitors to potentiate anti-tumor activity."

IO biomarker • Colon Cancer • Gastrointestinal Cancer • Hematological Malignancies • Oncology • Solid Tumor • CD44 • CD69 • CD8 • CD86 • IFNG • IL2RA • PD-L1 • SEC61G

Kezar Announces First Patient Dosed in Phase 1 Trial of KZR-261 in Advanced Solid Tumor Malignancies (Businesswire) - "Kezar Life Sciences, Inc...announced that the first patient has been dosed in KZR-261-101, a Phase 1 clinical trial evaluating KZR-261, a novel, broad-spectrum, anti-tumor agent that acts through direct interaction and inhibition of the Sec61 translocon...KZR-261-101 is a first-in-human, open-label, multicenter, Phase 1 study of KZR-261 in patients with solid tumor malignancies."

Trial status • Oncology • Solid Tumor

KZR-261 in Subjects With Advanced Solid Malignancies (clinicaltrials.gov) - P1; N=225; Not yet recruiting; Sponsor: Kezar Life Sciences, Inc.

Clinical • New P1 trial • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Melanoma • Oncology • Solid Tumor

Kezar Life Sciences Reports Second Quarter Financial Results and Provides Business Updates (Businesswire) - "Kezar submitted an investigational new drug (IND) application for KZR-261 to the U.S. Food and Drug Administration (FDA) in August 2021. The company plans to initiate a Phase 1 clinical trial of KZR-261, which will assess safety, tolerability and preliminary tumor activity of KZR-261 in solid tumors."

IND • Oncology • Solid Tumor

[VIRTUAL] Prioritizing tumor types for clinical study of novel Sec61 inhibitors by searching for expression profiles of sensitive cell lines in tumor sample databases (AACR 2021) - "Anti-tumor activity of KZR-834, a structurally related analog of KZR-261, was assessed in two cell line cytotoxicity screens totaling over 400 cell lines. Our novel small molecule inhibitors of Sec61 dependent protein translocation exhibit broad anti-tumor activity in vitro. Large cell line screens and bioinformatic analyses identifying tumor intrinsic sensitivities led to a prioritized list of potentially sensitive tumor types that has guided tumor type selection for our initial Phase 1 clinical trial of KZR-261 in solid tumors."

Preclinical • Cutaneous Melanoma • Diffuse Large B Cell Lymphoma • Lung Cancer • Melanoma • Mesothelioma • Oncology • Solid Tumor • CCND2

[VIRTUAL] Quantitative proteomic profiling of novel anti-cancer small molecule inhibitors of Sec61: Mechanistic investigation and biomarker discovery (AACR 2021) - "The structural analogs KZR-261 and KZR-834 were identified through a medicinal chemistry campaign and found to have broad in vitro anti-tumor activity and efficacy in mouse xenograft models. Flow cytometric analysis of PBMCs also showed a significant reduction in surface expression of those proteins in multiple cell populations.Our results highlight quantitative proteomic profiling as a valuable tool towards elucidation of the mechanism of pleiotropically-acting molecules. By assessing global proteomic changes in non-transformed cells, pharmacodynamic markers were identified that will be employed in the Phase 1 trial of KZR-261 in solid tumors."

Biomarker • Oncology • Solid Tumor • B2M • ICAM1 • IL7

Kezar Life Sciences Presents Preclinical Data with IND Candidate KZR-261 at American Association for Cancer Research (AACR) 2021 Virtual Annual Meeting (Businesswire) - "Kezar examined the activity of KZR-261, a small molecule inhibitor of the Sec 61 translocon, and a closely related representative molecule in hundreds of tumor cell lines. The objective was to compare drug activity and identify sensitivity to gene mutations and impact on gene expression levels. No single gene predicted the activity of KZR-261, consistent with the known impact of KZR-261 on multiple targets....Pending successful completion of drug product manufacturing, submission of an Investigational New Drug (IND) application is anticipated in mid-2021. A first-in-human Phase 1 study to evaluate the safety and anti-tumor activity of KZR-261 in patients with solid tumors is expected to commence shortly thereafter."

IND • New P1 trial • Preclinical • Oncology • Solid Tumor

Kezar Life Sciences Reports Third-Quarter 2020 Financial Results and Provides Business Updates (Businesswire) - "KZR-261, a first-in-class protein secretion inhibitor, targets the Sec61 translocon and has demonstrated broad anti-tumor activity in preclinical models of both solid and hematologic malignancies. Additional preclinical data further detailing the ability of novel small molecule Sec61 inhibitors to target multiple checkpoint proteins on various cell populations, thereby offering the potential of combination therapy in a single compound, are being presented during the 8th Annual Meeting of the International Cytokine & Interferon Society (Cytokines 2020) and the Society for the Immunotherapy of Cancer (SITC) in November 2020....An Investigational New Drug (IND) application for KZR-261 is on-track for a planned submission in the first quarter of 2021. The Phase 1 clinical trial will evaluate dose escalation and safety and tolerability in patients with solid tumors to begin shortly after IND acceptance."

IND • Preclinical • Oncology • Solid Tumor

[VIRTUAL] Preclinical evaluation of KZR-261, a novel small molecule inhibitor of Sec61. (ASCO 2020) - "Novel Sec61 inhibitors potently block expression of secreted and membrane proteins, translating into anti-tumor activity against many tumor types in vitro and in vivo, suggesting broad therapeutic potential. Clinical trials are being planned with KZR-261 to understand safety and early efficacy of this novel compound and therapeutic target. Research Funding: Kezar Life Sciences"

IO Biomarker • Preclinical • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Lung Cancer • Multiple Myeloma • Oncology • Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • EGFR