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    DRUG:

    zilovertamab (UC-961)

    i
    Other names: UC961, UC 961, UC-961, B013, B 013, B-013
    Company:
    Ho’ola Therapeutics, Oncternal Therap, Shanghai Pharma
    Drug class:
    ROR1 inhibitor
    Related drugs:
    21d
    A novel fully human anti-ROR1 antibody PBA-0405 optimized for ADCC, induces potent anti-tumor activity against both solid and hematological malignancies. (PubMed, Front Immunol)
    Our findings demonstrate that 22.0405.aF exhibits far superior ADCC activity compared to anti-ROR1 antibodies, e.g. zilovertamab and R12, tested in clinical trials thus far. 22.0405.aF displayed potent tumor cell killing, both in vitro and in vivo, and induced more potent killing of patient-derived malignant B-cells ex vivo compared to rituximab, without affecting healthy B-cells...These results underscore the therapeutic potential of 22.0405.aF as a promising immunotherapy for treatment of ROR1-positive B-cell malignancies. Notably, 22.0405.aF has recently completed Phase 0 clinical trials in patients with head and neck carcinomas and soft tissue sarcomas, paving the way for further clinical development.
    Journal • IO biomarker
    |
    ROR1 (Receptor Tyrosine Kinase Like Orphan Receptor 1)
    |
    Rituxan (rituximab) • zilovertamab (UC-961)
    9ms
    Cirmtuzumab Consolidation for Treatment of Patients With Detectable CLL on Venetoclax (clinicaltrials.gov)
    P2, N=5, Active, not recruiting, University of California, San Diego | Trial completion date: Jul 2025 --> Jul 2026 | Trial primary completion date: Jul 2025 --> Jul 2026
    Trial completion date • Trial primary completion date
    |
    Venclexta (venetoclax) • zilovertamab (UC-961)
    9ms
    Wnt5a induces ROR1 dependent NF-κB activation to enhance MMP-9 expression and invasiveness in chronic lymphocytic leukemia. (PubMed, Leukemia)
    Such effects of Wnt5a could not be inhibited by BTK inhibitors such as ibrutinib or zanubrutinib, but could be blocked by zilovertamab, a humanized mAb specific for ROR1. Moreover, siRNA directed silencing of MMP9 or treatment with an MMP-9 inhibitor (CAS 1177749-58-4) also blocked the invasive capability of CLL cells induced by Wnt5a. We conclude that Wnt5a-induced ROR1-signaling can induce expression of MMP-9 on CLL cells through activation of NF-κB, thereby enhancing the extravasation and lymphoid-tissue infiltration required for CLL cell trafficking.
    Journal
    |
    ROR1 (Receptor Tyrosine Kinase Like Orphan Receptor 1) • MMP9 (Matrix metallopeptidase 9)
    |
    Imbruvica (ibrutinib) • Brukinsa (zanubrutinib) • zilovertamab (UC-961)
    9ms
    Study of B013 and Nab-Paclitaxel for Locally Advanced or Metastatic Triple Negative Breast Cancer (clinicaltrials.gov)
    P2/3, N=62, Completed, Shanghai Jiaolian Drug Research and Development Co., Ltd | N=450 --> 62 | Trial completion date: Dec 2026 --> Sep 2024 | Recruiting --> Completed | Trial primary completion date: Jun 2025 --> Sep 2024
    Trial completion • Enrollment change • Trial completion date • Trial primary completion date
    |
    albumin-bound paclitaxel • zilovertamab (UC-961)
    12ms
    Study of B013 and Nab-Paclitaxel for Locally Advanced or Metastatic Triple Negative Breast Cancer (clinicaltrials.gov)
    P2/3, N=450, Recruiting, Shanghai Jiaolian Drug Research and Development Co., Ltd | Trial primary completion date: Dec 2024 --> Jun 2025
    Trial primary completion date
    |
    albumin-bound paclitaxel • zilovertamab (UC-961)
    over1year
    CirmD: Study of Docetaxel Combined with Cirmtuzumab in Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov)
    P1, N=6, Terminated, University of California, San Diego | N=32 --> 6 | Trial completion date: Feb 2026 --> Oct 2024 | Recruiting --> Terminated | Trial primary completion date: Feb 2025 --> Oct 2024; Oncternal closing clinical trial operations.
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Metastases
    |
    docetaxel • zilovertamab (UC-961)
    over1year
    A Study of Cirmtuzumab and Ibrutinib in Patients With B-Cell Lymphoid Malignancies (clinicaltrials.gov)
    P1/2, N=102, Completed, Oncternal Therapeutics, Inc | Active, not recruiting --> Completed
    Trial completion
    |
    BCL2 (B-cell CLL/lymphoma 2)
    |
    Imbruvica (ibrutinib) • zilovertamab (UC-961)
    over1year
    A Study of B013 in Combination With Paclitaxel in Patients With Platinum-resistant Recurrent Ovarian Cancer. (clinicaltrials.gov)
    P2, N=90, Not yet recruiting, Shanghai Jiaolian Drug Research and Development Co., Ltd
    New P2 trial • Combination therapy
    |
    paclitaxel • zilovertamab (UC-961)
    almost2years
    Study of Cirmtuzumab and Paclitaxel for Metastatic or Locally Advanced, Unresectable Breast Cancer (clinicaltrials.gov)
    P1, N=22, Completed, Barbara Parker, MD | Active, not recruiting --> Completed | Phase classification: P1b --> P1
    Trial completion • Phase classification • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
    |
    HER-2 negative • ER negative • ER positive + PGR positive • PGR positive • PGR negative
    |
    paclitaxel • zilovertamab (UC-961)
    almost2years
    A phase 1b study of zilovertamab in combination with paclitaxel for locally advanced/unresectable or metastatic Her2-negative breast cancer. (PubMed, Breast Cancer Res)
    The combination of zilovertamab and paclitaxel was safe and well tolerated in heavily pre-treated advanced breast cancer patients. Further evaluation of ROR1 targeting in breast cancer patients with zilovertamab is warranted.
    P1 data • Journal • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ROR1 (Receptor Tyrosine Kinase Like Orphan Receptor 1)
    |
    HER-2 negative
    |
    paclitaxel • zilovertamab (UC-961)
    2years
    Study of Docetaxel Combined With Cirmtuzumab in Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov)
    P1, N=32, Recruiting, University of California, San Diego
    Trial completion date • Trial primary completion date • Metastases
    |
    docetaxel • zilovertamab (UC-961)
    2years
    A Study of Cirmtuzumab and Ibrutinib in Patients With B-Cell Lymphoid Malignancies (clinicaltrials.gov)
    P1/2, N=102, Active, not recruiting, Oncternal Therapeutics, Inc | Phase classification: P1b/2 --> P1/2
    Phase classification
    |
    BCL2 (B-cell CLL/lymphoma 2)
    |
    Imbruvica (ibrutinib) • zilovertamab (UC-961)