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    DRUG:

    azenosertib (ZN-c3)

    i
    Other names: ZN-c3, ZN c3, ZNc3
    Company:
    Zentalis Pharma
    Drug class:
    WEE1 inhibitor
    Related drugs:
    6d
    ZAP-IT: ZN-c3 + Carboplatin + Pembrolizumab in mTNBC (clinicaltrials.gov)
    P1, N=7, Terminated, Filipa Lynce, MD | Phase classification: P1/2 --> P1
    Phase classification
    |
    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • CD4 (CD4 Molecule)
    |
    HER-2 negative
    |
    Keytruda (pembrolizumab) • carboplatin • azenosertib (ZN-c3)
    15d
    A Possibility of Synthetic Lethality: Wee1 Kinase as a Promising Treating Target for Cancer. (PubMed, Med Res Rev)
    Wee1 is the fastest progressing member in clinical research, and its inhibitors such as AZD-1775 and ZN-c3 are under clinical evaluation. We further summarize design principles for targeted degradation of Wee1 and outline combination strategies grounded in synthetic lethality, and we curate recent preclinical and ongoing clinical advances with discussion of biomarker-guided enrollment and dosing schedules. By linking structural mechanisms to pharmacology and clinical placement, this review provides an actionable framework for next-generation Wee1-directed drug design and translation in oncology.
    Review • Journal
    |
    TP53 (Tumor protein P53) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
    |
    adavosertib (AZD1775) • azenosertib (ZN-c3)
    19d
    ZAP-IT: ZN-c3 + Carboplatin + Pembrolizumab in mTNBC (clinicaltrials.gov)
    P1/2, N=7, Terminated, Filipa Lynce, MD | N=78 --> 7 | Trial completion date: Sep 2029 --> Feb 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Mar 2027 --> Feb 2026; Zentalis terminated contract due to concern for toxicity safety from previously reported serious adverse events.
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • CD4 (CD4 Molecule)
    |
    HER-2 negative
    |
    Keytruda (pembrolizumab) • carboplatin • azenosertib (ZN-c3)
    22d
    ASPENOVA: A Study of Azenosertib (ZN-c3) Versus Investigator's Choice Chemotherapy in Subjects With Platinum-Resistant High-Grade Serous Ovarian, Primary Peritoneal, or Fallopian Tube Cancers Positive for Cyclin E1 Protein Expression (clinicaltrials.gov)
    P3, N=420, Recruiting, K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc | Not yet recruiting --> Recruiting
    Enrollment open • Platinum resistant
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CCNE1 (Cyclin E1) • BRCA (Breast cancer early onset)
    |
    BRCA2 mutation • BRCA1 mutation • BRCA mutation
    |
    paclitaxel • azenosertib (ZN-c3)
    2ms
    Discovery of APO-50815, a potent WEE1 kinase inhibitor with exceptional efficacy against patient-derived colorectal cancer organoids. (PubMed, Eur J Med Chem)
    When tested against TP53-mutated colorectal cancer (CRC) patient-derived organoids (PDOs) grown from peritoneal and liver metastases, 14 exhibited outstanding anticancer efficacy, surpassing previously reported branched alkane counterpart 3, as well as clinical candidates AZD1775 (1) and ZN-c3 (2). Against primary CRC PDOs (TP53-WT, BRAF-V600E, KRAS-WT), 14 profoundly elevated DNA damage and replication stress compared to 1, while amplifying cellular apoptosis, confirming a broadly similar but superior mode of action. Owing to its highly selective and exemplary anticancer efficacy, 14 represents a valuable tool compound for drug testing investigations against primary and metastatic CRCs, especially in the context of PDOs.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)
    |
    TP53 mutation • BRAF V600E • KRAS mutation • BRAF V600 • TP53 wild-type • KRAS wild-type
    |
    adavosertib (AZD1775) • azenosertib (ZN-c3)
    2ms
    ASPENOVA: A Study of Azenosertib (ZN-c3) Versus Investigator's Choice Chemotherapy in Subjects With Platinum-Resistant High-Grade Serous Ovarian, Primary Peritoneal, or Fallopian Tube Cancers Positive for Cyclin E1 Protein Expression (clinicaltrials.gov)
    P3, N=420, Not yet recruiting, K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
    New P3 trial • Platinum resistant
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CCNE1 (Cyclin E1) • BRCA (Breast cancer early onset)
    |
    BRCA2 mutation • BRCA1 mutation • BRCA mutation
    |
    paclitaxel • azenosertib (ZN-c3)
    2ms
    DENALI: A Study of Azenosertib (ZN-c3) in Subjects With Platinum-Resistant High-Grade Serous Ovarian, Fallopian Tube or Primary Peritoneal Cancer (clinicaltrials.gov)
    P2, N=310, Recruiting, K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc | N=170 --> 310
    Enrollment change • Platinum resistant
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CCNE1 (Cyclin E1) • BRCA (Breast cancer early onset)
    |
    BRCA2 mutation • BRCA1 mutation • BRCA mutation
    |
    azenosertib (ZN-c3)
    2ms
    ZN-c3-002: A Study of Azenosertib (ZN-c3) in Patients With Ovarian Cancer (clinicaltrials.gov)
    P1, N=172, Recruiting, K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc | Trial completion date: Feb 2027 --> Jun 2028 | Trial primary completion date: Dec 2024 --> Jun 2028
    Trial completion date • Trial primary completion date
    |
    Avastin (bevacizumab) • carboplatin • gemcitabine • paclitaxel • pegylated liposomal doxorubicin • azenosertib (ZN-c3)
    2ms
    ZN-c3-003: A Study of Azenosertib (ZN-c3) in Combination With Gemcitabine in Subjects With Osteosarcoma (clinicaltrials.gov)
    P1, N=31, Completed, K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc | Phase classification: P1/2 --> P1
    Phase classification
    |
    gemcitabine • azenosertib (ZN-c3)
    3ms
    TETON: A Study of Azenosertib (ZN-c3) in Women With Recurrent or Persistent Uterine Serous Carcinoma (clinicaltrials.gov)
    P2, N=92, Completed, K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc | Recruiting --> Completed | Trial completion date: May 2025 --> Oct 2025 | Trial primary completion date: Nov 2024 --> Oct 2025
    Trial completion • Trial completion date • Trial primary completion date
    |
    HER-2 positive
    |
    azenosertib (ZN-c3)
    3ms
    ZN-c3-003: A Study of Azenosertib (ZN-c3) in Combination With Gemcitabine in Subjects With Osteosarcoma (clinicaltrials.gov)
    P1/2, N=31, Completed, K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc | Active, not recruiting --> Completed | N=84 --> 31
    Trial completion • Enrollment change
    |
    gemcitabine • azenosertib (ZN-c3)
    3ms
    MAMMOTH: A Study of Azenosertib (ZN-c3) and Niraparib in Subjects With Platinum-Resistant Ovarian Cancer (clinicaltrials.gov)
    P1/2, N=117, Completed, K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc | Active, not recruiting --> Completed | Trial completion date: May 2025 --> Jan 2026 | Trial primary completion date: May 2025 --> Oct 2025
    Trial completion • Trial completion date • Trial primary completion date • Platinum resistant
    |
    Zejula (niraparib) • azenosertib (ZN-c3)