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    DRUG:

    pegvorhyaluronidase alfa (PEGPH20)

    i
    Other names: PEGylated Recombinant Human Hyaluronidase, PEG PH20, PEG rHuPH-20, PEGPH20, PEG rHuPH20, pegylated rHuPH20
    Company:
    Halozyme, Nektar Therap
    Drug class:
    Hyaluronidase stimulant
    Related drugs:
    9d
    Study Of Gemcitabine, Nab-paclitaxel, PEGPH20 and Rivaroxaban for Advanced Pancreatic Adenocarcinoma (clinicaltrials.gov)
    P=N/A, N=110, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2025 --> Oct 2026
    Trial completion date • Trial primary completion date
    |
    gemcitabine • albumin-bound paclitaxel • pegvorhyaluronidase alfa (PEGPH20)
    5ms
    Pancreatic Neuroendocrine Tumors Secrete Apolipoprotein E to Induce Tip Endothelial Cells That Remodel the Tumor-Stroma Ratio and Promote Cancer Progression. (PubMed, Cancer Res)
    Importantly, mTOR inhibitors synergistically enhanced the antitumor effects of stroma-targeting PEGPH20 in vivo in pNETs. Overall, this study revealed that cancer cell-derived ApoE could induce TipECs to remodel the TSR and that mTOR inhibitors could increase the efficacy of stroma-targeting therapies. Secretion of ApoE by pancreatic neuroendocrine tumor cells engenders a stroma-rich microenvironment, which can be reversed with mTOR inhibitors as part of combination strategies targeting the tumor stroma.
    Journal
    |
    APOE (Apolipoprotein E) • ATF6 (Activating Transcription Factor 6)
    |
    pegvorhyaluronidase alfa (PEGPH20)
    7ms
    MORPHEUS-EC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Patients With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Cancer (G/GEJ) or Esophageal Cancer (Morpheus-Gastric and Esophageal Cancer) (clinicaltrials.gov)
    P1/2, N=410, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Jun 2025 --> Sep 2025 | Trial primary completion date: Jun 2025 --> Sep 2025
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2)
    |
    HER-2 negative • HER-2 expression
    |
    cisplatin • Tecentriq (atezolizumab) • paclitaxel • 5-fluorouracil • Cotellic (cobimetinib) • Cyramza (ramucirumab) • oxaliplatin • leucovorin calcium • tiragolumab (RG6058) • pegvorhyaluronidase alfa (PEGPH20) • Aphexda (motixafortide)
    8ms
    MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov)
    P1/2, N=341, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed
    Trial completion
    |
    PD-L1 (Programmed death ligand 1)
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • gemcitabine • 5-fluorouracil • Cotellic (cobimetinib) • albumin-bound paclitaxel • oxaliplatin • leucovorin calcium • Actemra IV (tocilizumab) • tiragolumab (RG6058) • etrumadenant (AB928) • pegvorhyaluronidase alfa (PEGPH20) • Aphexda (motixafortide) • selicrelumab (RG7876) • simlukafusp alfa (RG7461)
    1year
    MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov)
    P1/2, N=340, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Oct 2026 --> Jan 2025 | Trial primary completion date: Oct 2025 --> Jan 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • gemcitabine • 5-fluorouracil • Cotellic (cobimetinib) • albumin-bound paclitaxel • oxaliplatin • leucovorin calcium • Actemra IV (tocilizumab) • tiragolumab (RG6058) • etrumadenant (AB928) • pegvorhyaluronidase alfa (PEGPH20) • Aphexda (motixafortide) • selicrelumab (RG7876) • simlukafusp alfa (RG7461)
    1year
    MORPHEUS-EC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Patients With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Cancer (G/GEJ) or Esophageal Cancer (Morpheus-Gastric and Esophageal Cancer) (clinicaltrials.gov)
    P1/2, N=410, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Aug 2024 --> Apr 2025
    Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2)
    |
    HER-2 negative • HER-2 expression
    |
    cisplatin • Tecentriq (atezolizumab) • paclitaxel • 5-fluorouracil • Cotellic (cobimetinib) • Cyramza (ramucirumab) • oxaliplatin • leucovorin calcium • tiragolumab (RG6058) • pegvorhyaluronidase alfa (PEGPH20) • Aphexda (motixafortide)
    over1year
    Hyaluronidase improves the efficacy of nab-paclitaxel after prolonged angiogenesis inhibition in preclinical models for esophagogastric cancer. (PubMed, Biomed Pharmacother)
    These findings suggest that the mechanical barrier of HA is the major reason responsible for the resistance developed during prolonged anti-angiogenesis in EGC. Incorporating PEGPH20 into the existing treatment regimen is promising to improve outcomes for patients with EGC.
    Preclinical • Journal
    |
    CD31 (Platelet and endothelial cell adhesion molecule 1) • PECAM1 (Platelet And Endothelial Cell Adhesion Molecule 1)
    |
    albumin-bound paclitaxel • DC101 • nitroglycerin • pegvorhyaluronidase alfa (PEGPH20)
    over1year
    Study Of Gemcitabine, Nab-paclitaxel, PEGPH20 and Rivaroxaban for Advanced Pancreatic Adenocarcinoma (clinicaltrials.gov)
    P=N/A, N=110, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    gemcitabine • albumin-bound paclitaxel • pegvorhyaluronidase alfa (PEGPH20)
    almost2years
    S1313, PEGPH20 in Treating Patients With Newly Diagnosed Metastatic Pancreatic Cancer (clinicaltrials.gov)
    P1/2, N=126, Completed, SWOG Cancer Research Network | Active, not recruiting --> Completed
    Trial completion
    |
    5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium • pegvorhyaluronidase alfa (PEGPH20)
    2years
    MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov)
    P1/2, N=340, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    PD-L1 (Programmed death ligand 1)
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • gemcitabine • 5-fluorouracil • Cotellic (cobimetinib) • albumin-bound paclitaxel • oxaliplatin • leucovorin calcium • Actemra IV (tocilizumab) • tiragolumab (RG6058) • etrumadenant (AB928) • pegvorhyaluronidase alfa (PEGPH20) • Aphexda (motixafortide) • selicrelumab (RG7876) • simlukafusp alfa (RG7461)
    2years
    Monitor PDAC Tumor Response to Stroma-Targeting Therapy using CEST MRI (RSNA 2023)
    We have evaluated dextran-enhanced CEST MRI’s ability to assess tumor responses to stroma-targeting therapy. Our data indicates that 10 kD dextran is suitable for monitoring the tumor responses to PEGPH20. Reference : 1.
    Stroma
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS G12D • KRAS G12
    |
    pegvorhyaluronidase alfa (PEGPH20)
    2years
    MORPHEUS-GC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Patients With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Cancer (G/GEJ) or Esophageal Cancer (Morpheus-Gastric and Esophageal Cancer) (clinicaltrials.gov)
    P1/2, N=410, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting
    Enrollment closed • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2)
    |
    HER-2 negative • HER-2 expression
    |
    cisplatin • Tecentriq (atezolizumab) • paclitaxel • 5-fluorouracil • Cotellic (cobimetinib) • Cyramza (ramucirumab) • oxaliplatin • leucovorin calcium • tiragolumab (RG6058) • pegvorhyaluronidase alfa (PEGPH20) • Aphexda (motixafortide)