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    DRUG CLASS:

    WEE1 inhibitor

    Related drugs:
    2d
    REFMAL 412: Safety, Tolerability and Pharmacokinetics of AZD1775 (Adavosertib) Plus MEDI4736 (Durvalumab) in Patients With Advanced Solid Tumours (clinicaltrials.gov)
    P1, N=56, Completed, AstraZeneca | Active, not recruiting --> Completed
    Trial completion
    |
    Imfinzi (durvalumab) • adavosertib (AZD1775)
    5d
    Azenosertib in Uterine Serous Carcinoma: Biomarker Study (clinicaltrials.gov)
    P2, N=25, Recruiting, Joyce Liu, MD | Trial completion date: Jan 2027 --> Jan 2028 | Trial primary completion date: Jan 2026 --> Jan 2027
    Trial completion date • Trial primary completion date
    |
    PD-L1 (Programmed death ligand 1)
    |
    MSI-H/dMMR
    |
    azenosertib (ZN-c3)
    8d
    A Study to Evaluate Safety and Preliminary Anti-tumor Activity of Debio 0123 as Monotherapy in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=66, Active, not recruiting, Debiopharm International SA | N=155 --> 66 | Trial completion date: Jun 2027 --> Apr 2026
    Enrollment change • Trial completion date
    |
    CCNE1 (Cyclin E1)
    |
    Debio 0123
    9d
    ROR1-PI3K/AKT signaling drives adaptive resistance to cell cycle blockade in TP53 mutated ovarian cancer. (PubMed, Cell Death Dis)
    In this study, we developed long-term resistant (lt-res, several months) pre-clinical models of two drugs inducing mitotic arrest in TP53-mutated cells: adavosertib (ADA), an investigational WEE1 inhibitor targeting the DNA damage response and currently evaluated in clinical trials, and paclitaxel (PTX), a widely used chemotherapeutic agent in cancer care targeting microtubules. Notably, upregulation of receptor tyrosine kinases, such as ROR1, was observed in both ADA and PTX lt-res models with activated PI3K/AKT signaling. Targeting ROR1 with zilovertamab-vedotin, a monoclonal antibody-drug conjugate, resulted in enhanced cytotoxicity, demonstrating a new approach against recurrent drug-resistant ovarian cancer.
    Journal
    |
    TP53 (Tumor protein P53) • ROR1 (Receptor Tyrosine Kinase Like Orphan Receptor 1)
    |
    TP53 mutation
    |
    paclitaxel • adavosertib (AZD1775) • zilovertamab vedotin (MK-2140)
    1m
    A Study to Evaluate Safety and Preliminary Anti-tumor Activity of Debio 0123 as Monotherapy in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=155, Active, not recruiting, Debiopharm International SA | Trial primary completion date: Jan 2026 --> Apr 2026
    Trial primary completion date
    |
    CCNE1 (Cyclin E1)
    |
    Debio 0123
    1m
    Testing the Combination of the Anticancer Drugs Trastuzumab Deruxtecan (DS-8201a) and Azenosertib (ZN-c3) in Patients With Stomach or Other Solid Tumors (clinicaltrials.gov)
    P1, N=48, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended
    Trial suspension
    |
    CCNE1 (Cyclin E1)
    |
    HER-2 amplification • HER-2 expression
    |
    Enhertu (fam-trastuzumab deruxtecan-nxki) • azenosertib (ZN-c3)
    1m
    Preclinical drug screen identifies WEE1 inhibitor and vinca alkaloid as a combination treatment concept for Li-Fraumeni syndrome medulloblastoma. (PubMed, iScience)
    The combination of WEE1 inhibitor adavosertib and vinca alkaloid vincristine demonstrated the highest activity, which was validated in TP53mut SHH-MB patient-derived organoids. Despite the drugs' limited efficacy in the in vivo PDX model, WEE1 knockdown led to significant growth reduction in in vitro and in vivo TP53mut SHH-MB models. Our findings identify WEE1 as a promising target in LFS SHH-MB, suggesting its inhibition combined with vincristine treatment as a potential chemotherapeutic strategy.
    Preclinical • Journal
    |
    TP53 (Tumor protein P53)
    |
    TP53 mutation
    |
    adavosertib (AZD1775) • vincristine
    1m
    MYTHIC: Study of Lunresertib Alone or in Combination With RP-3500 or Debio 0123 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=464, Recruiting, Debiopharm International SA | Trial completion date: Dec 2026 --> Jun 2028 | Trial primary completion date: Jun 2026 --> Dec 2027
    Trial completion date • Trial primary completion date
    |
    CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • MUC16 (Mucin 16, Cell Surface Associated) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
    |
    lunresertib (RP-6306) • Debio 0123 • camonsertib (RP-3500)
    1m
    Transcription termination counteracts DNA damage after WEE1 inhibition. (PubMed, Nucleic Acids Res)
    Elevated expression of CPSF73 is associated with aggressive disease in prostate cancer patients, and combining JTE-607 with adavosertib synergistically reduced prostate cancer cell survival. Our findings suggest that transcription termination helps prevent toxic conflicts between transcription and replication following increased replication initiation caused by WEE1 inhibition.
    Journal
    |
    DDX5 (DEAD-Box Helicase 5) • CDC73 (Cell Division Cycle 73) • PAF1 (PAF1 Homolog, Paf1/RNA Polymerase II Complex Component)
    |
    adavosertib (AZD1775)
    2ms
    EFFORT: Adavosertib With or Without Olaparib in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov)
    P2, N=96, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026
    Trial completion date • Trial primary completion date
    |
    HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
    |
    HRD • BRCA mutation
    |
    Lynparza (olaparib) • adavosertib (AZD1775) • ceralasertib (AZD6738)
    2ms
    ZAP-IT: ZN-c3 + Carboplatin + Pembrolizumab in mTNBC (clinicaltrials.gov)
    P1/2, N=78, Active, not recruiting, Filipa Lynce, MD | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • CD4 (CD4 Molecule)
    |
    HER-2 negative
    |
    Keytruda (pembrolizumab) • carboplatin • azenosertib (ZN-c3)
    2ms
    AZD1775 in Women With Recurrent or Persistent Uterine Serous Carcinoma or Uterine Carcinosarcoma (clinicaltrials.gov)
    P2, N=49, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Dec 2026 --> Jul 2027 | Trial primary completion date: Dec 2025 --> Jul 2026
    Trial completion date • Trial primary completion date
    |
    adavosertib (AZD1775)