Azenosertib

Shows activity

Also known as:

KP-2638

Cancer types include:

ovarian cancer stomach cancer uterine cancer

TrialFetch AI Analysis

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Overview

Azenosertib (also called ZN-c3 or KP-2638) is an investigational oral cancer drug. Human results are available, chiefly from early-phase, single-arm studies in platinum-resistant ovarian cancer and other advanced solid tumors. These studies show responses in some patients but cannot establish how much benefit azenosertib adds over existing treatment. A phase 3 ovarian-cancer trial is underway. (ctis.eu)

Mechanism of action

Azenosertib inhibits WEE1 kinase, which helps regulate cell-cycle checkpoints. In preclinical studies, WEE1 inhibition increased DNA-damage markers; tumors with high cyclin E1 expression appeared particularly sensitive. Cyclin E1 is therefore being studied as a marker for selecting patients, but its clinical predictive value is not yet established. (pubmed.ncbi.nlm.nih.gov)

Efficacy

Azenosertib alone: In a phase 1 study, the objective response rate was 12/58 (21%) among patients with platinum-resistant ovarian cancer receiving intermittent dosing, and 8/23 (35%) among those whose tumors were cyclin E1-positive. The corresponding rates in uterine serous carcinoma were 5/19 (26%) and 4/11 (36%). These subgroup results involve small numbers of patients. (aacrjournals.org)
With paclitaxel: A 2026 phase 1b abstract reported responses in 18/46 patients (39%) with platinum-resistant ovarian cancer; median response duration was 5.6 months. Because the study had no paclitaxel-only comparison group, the contribution of azenosertib cannot be determined from this result. (ascopubs.org)

Safety

In the 193-patient phase 1 monotherapy analysis, the most common treatment-related adverse events were nausea (61%), fatigue (59%) and diarrhea (52%). Grade 3 or worse treatment-related fatigue and neutropenia each occurred in 13%; anemia and thrombocytopenia each occurred in 11%. Treatment-related events led to discontinuation in 5%, and one death of unknown cause was reported. In the paclitaxel-combination study, grade 3 or worse treatment-related neutropenia occurred in 30% and anemia in 20%. (aacrjournals.org)

Active trials using Azenosertib

Found 4 active trials using this drug:

A Randomized, Open-Label Phase 3 Study of Azenosertib Versus Investigator's Choice of Chemotherapy in Platinum-Resistant High-Grade Serous Ovarian, Primary Peritoneal, or Fallopian Tube Cancers Positive for Cyclin E1 Protein Expression

Sponsor: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc (industry) Phase: 3 Start date: April 17, 2026

TrialFetch AI summary: Women with measurable, cyclin E1 protein–positive, platinum-resistant high-grade serous ovarian, primary peritoneal, or fallopian tube cancer and 1–3 prior treatment regimens (up to 4 after mirvetuximab) are randomized to oral azenosertib, a WEE1 checkpoint kinase inhibitor, or investigator’s choice of chemotherapy. Primary platinum-refractory disease is excluded.

ClinicalTrials.gov ID: NCT07546500

A Biomarker Study of the Wee1 Inhibitor Azenosertib (ZN-c3) in Women With Recurrent or Persistent Uterine Serous Carcinoma

Sponsor: Joyce Liu, MD (other) Phase: 2 Start date: March 5, 2025

TrialFetch AI summary: Adults with measurable recurrent or persistent uterine carcinoma containing a serous component after platinum-based chemotherapy receive oral azenosertib, a WEE1 kinase inhibitor that increases replication stress and DNA damage. The single-arm study uses paired tumor biopsies to assess whether changes in replication fork speed are associated with response or 6-month progression-free survival.

ClinicalTrials.gov ID: NCT06369155

Phase 1 Study of Trastuzumab Deruxtecan (DS-8201a) in Combination With Azenosertib (ZN-c3) in HER2-Expressing/Amplified Cyclin E-Amplified Gastric/Gastroesophageal Junction Cancer and Other Solid Tumors With HER2 Expression

Sponsor: National Cancer Institute (NCI) (federal) Phase: 1 Start date: Feb. 3, 2025

TrialFetch AI summary: Adults with previously treated, unresectable or metastatic HER2-expressing/amplified solid tumors who have not received trastuzumab deruxtecan are eligible for dose escalation; expansion is limited to CCNE1-amplified gastric or GEJ cancer. All patients receive trastuzumab deruxtecan, a HER2-directed antibody–drug conjugate delivering a topoisomerase I inhibitor, plus azenosertib, an investigational WEE1 inhibitor.

ClinicalTrials.gov ID: NCT06364410

A Phase 2 Open-Label, Multicenter Study To Evaluate Efficacy And Safety Of ZN-c3 In Subjects With High-Grade Serous Ovarian, Fallopian Tube, Or Primary Peritoneal Cancer (DENALI / ZN-c3-005 / GOG-3066)

Sponsor: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc (industry) Phase: 2 Start date: Feb. 17, 2022

TrialFetch AI summary: Adults with measurable, platinum-resistant high-grade serous ovarian, fallopian tube, or primary peritoneal cancer are treated with oral azenosertib, an investigational WEE1 kinase inhibitor that disrupts the DNA-damage checkpoint. The enrolling portion requires cyclin E1-positive tumors and compares two azenosertib doses without a standard-treatment control arm.

ClinicalTrials.gov ID: NCT05128825