^
    3ms
    Antitumor Activity of Neoadjuvant Chemotherapy with or Without HCW9218 in Metastatic Advanced Stage Ovarian Cancer (clinicaltrials.gov)
    P2, N=0, Withdrawn, Haider Mahdi | N=33 --> 0 | Recruiting --> Withdrawn
    Enrollment change • Trial withdrawal • Metastases
    |
    CD8 (cluster of differentiation 8)
    |
    carboplatin • paclitaxel • HCW9218
    7ms
    Antitumor Activity of Neoadjuvant Chemotherapy With or Without HCW9218 in Metastatic Advanced Stage Ovarian Cancer (clinicaltrials.gov)
    P2, N=33, Recruiting, Haider Mahdi | Not yet recruiting --> Recruiting | Phase classification: P1b --> P2 | Trial completion date: Jan 2027 --> Jan 2028 | Trial primary completion date: Jan 2024 --> May 2026
    Enrollment open • Phase classification • Trial completion date • Trial primary completion date • Metastases
    |
    CD8 (cluster of differentiation 8)
    |
    carboplatin • paclitaxel • HCW9218
    10ms
    HCW9218 in Select Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=18, Active, not recruiting, Masonic Cancer Center, University of Minnesota | Recruiting --> Active, not recruiting | Trial completion date: Jan 2027 --> Feb 2026 | Trial primary completion date: Jan 2027 --> Feb 2025
    Enrollment closed • Trial completion date • Trial primary completion date • Metastases
    |
    HCW9218
    10ms
    HCW9218 for Advanced Pancreatic Cancer (clinicaltrials.gov)
    P1/2, N=60, Active, not recruiting, HCW Biologics | Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P1/2
    Enrollment closed • Phase classification • Metastases
    |
    HCW9218
    over1year
    Pre-clinical and first-in-human studies of HCW9218, a bifunctional TGF-β antagonist/IL-15 protein complex, in advanced solid tumors (SITC 2023)
    5 mg/kg in heavily pretreated advanced solid tumor patients resulted in immune cell activation, proliferation, and infiltration into the tumor microenvironment without causing unacceptable toxicity. HCW treatment presents a promising approach to enhancing the antitumor activity of immune checkpoint inhibitors in patients with solid tumors.
    P1 data • Preclinical • IO biomarker • Metastases
    |
    CD8 (cluster of differentiation 8) • TGFB1 (Transforming Growth Factor Beta 1) • IL15 (Interleukin 15)
    |
    HCW9218
    almost2years
    Bifunctional immunotherapeutic HCW9218 facilitates recruitment of immune cells from tumor draining lymph nodes to promote antitumor activity and enhance checkpoint blockade efficacy in solid tumors (AACR 2023)
    Collectively, the results of this studydemonstrated that HCW9218 treatment of mice bearing solid tumors resulted in modulating the TdLN immune landscape and invigorating T cells for enhanced checkpoint blockade therapy. HCW9218 are currently in two clinical trials (clinicaltrials.org: NCT05322408, NCT05304936) against chemo-resistant/refractory solid tumors.
    Clinical • Checkpoint inhibition • Checkpoint block • Immune cell
    |
    CD8 (cluster of differentiation 8) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • TGFB1 (Transforming Growth Factor Beta 1) • IL15 (Interleukin 15)
    |
    HCW9218
    2years
    A phase I study of HCW9218, a bifunctional TGF-β Antagonist/IL-15 protein complex, in advanced solid tumors (SITC 2022)
    Conclusions HCW9218 safely and robustly expands NK cells after a single dose and escalation continues as planned to DL2 (0.5 mg/kg). Trial Registration NCT05322408
    P1 data
    |
    CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • NCAM1 (Neural cell adhesion molecule 1) • TGFB1 (Transforming Growth Factor Beta 1) • IL15 (Interleukin 15) • IL1B (Interleukin 1, beta)
    |
    HCW9218
    almost3years
    Immunotherapeutic HCW9218 augments anti-tumor activity of chemotherapy via NK cell mediated reduction of therapy induced senescent cells. (PubMed, Mol Ther)
    Herein, we showed that the immunotherapeutic HCW9218, comprising TGF-β receptor II and IL-15/IL-15 receptor α domains, enhanced metabolic and cytotoxic activities of immune cells and reduced TIS tumor cells in vivo to improve the efficacy of docetaxel and gemcitabine plus nab-paclitaxel against B16F10 melanoma and SW1990 pancreatic tumors, respectively. We also show that HCW9218 treatment decreased TIS cells and lowered SASP factors in off-target tissues caused by chemotherapy of tumor-bearing mice. Collectively, HCW9218 has the potential to significantly enhance anti-tumor efficacy of chemotherapy, therapeutic antibodies, and checkpoint blockade by eliminating TIS cancer cells while reducing TIS-mediated proinflammatory side effects in normal tissues.
    Journal
    |
    TGFB1 (Transforming Growth Factor Beta 1)
    |
    gemcitabine • docetaxel • albumin-bound paclitaxel • HCW9218