^
    2ms
    Pixatimod (PG545) Plus Nivolumab in PD-1 Relapsed/Refractory Metastatic Melanoma and NSCLC and With Nivolumab and Low-dose Cyclophosphamide in MSS Metastatic Colorectal Carcinoma (mCRC) (clinicaltrials.gov)
    P2, N=14, Active, not recruiting, Diwakar Davar | Trial completion date: Sep 2027 --> Aug 2025 | Trial primary completion date: Sep 2025 --> Dec 2024
    Trial completion date • Trial primary completion date • Combination therapy • Pan tumor • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    KRAS mutation • EGFR mutation • BRAF mutation • KRAS wild-type • RAS wild-type
    |
    Opdivo (nivolumab) • cyclophosphamide • pixatimod (PG545)
    5ms
    Pixatimod (PG545) Plus Nivolumab in PD-1 Relapsed/Refractory Metastatic Melanoma and NSCLC and With Nivolumab and Low-dose Cyclophosphamide in MSS Metastatic Colorectal Carcinoma (mCRC) (clinicaltrials.gov)
    P2, N=14, Active, not recruiting, Diwakar Davar | Recruiting --> Active, not recruiting | Phase classification: P2a --> P2 | N=61 --> 14 | Trial completion date: Dec 2029 --> Sep 2027 | Trial primary completion date: Nov 2026 --> Sep 2025
    Enrollment closed • Phase classification • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Pan tumor • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    KRAS mutation • EGFR mutation • BRAF mutation • KRAS wild-type • RAS wild-type
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    Opdivo (nivolumab) • cyclophosphamide • pixatimod (PG545)
    8ms
    PG545 sensitizes ovarian cancer cells to PARP inhibitors through modulation of RAD51-DEK interaction. (PubMed, Oncogene)
    Synergistic antitumor activity of the PG545/rucaparib combination was likewise observed in an immunocompetent syngeneic ID8F3 OC model. Collectively, these results suggest that targeting DEK-HSPG interactions in the TME through the use of PG545 may be a novel method of inhibiting DNA repair and sensitizing cells to PARPis.
    Journal • PARP Biomarker
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    HRD (Homologous Recombination Deficiency) • RAD51 (RAD51 Homolog A)
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    Rubraca (rucaparib) • pixatimod (PG545)
    1year
    Pixatimod (PG545) Plus Nivolumab in PD-1 Relapsed/Refractory Metastatic Melanoma and NSCLC and With Nivolumab and Low-dose Cyclophosphamide in MSS Metastatic Colorectal Carcinoma (mCRC) (clinicaltrials.gov)
    P2a, N=61, Recruiting, Diwakar Davar | Trial completion date: Sep 2026 --> Dec 2029 | Trial primary completion date: Nov 2023 --> Nov 2026
    Trial completion date • Trial primary completion date • Combination therapy • IO biomarker • Pan tumor • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    KRAS mutation • EGFR mutation • BRAF mutation • KRAS wild-type • RAS wild-type
    |
    Opdivo (nivolumab) • cyclophosphamide • pixatimod (PG545)
    over1year
    Phase Ib open-label, multicenter study of pixatimod, an activator of TLR9, in combination with nivolumab in subjects with microsatellite-stable metastatic colorectal cancer, metastatic pancreatic ductal adenocarcinoma and other solid tumors. (PubMed, J Immunother Cancer)
    Pixatimod is well tolerated at 25 mg in combination with nivolumab. The efficacy signal and pharmacodynamic changes in MSS mCRC warrants further investigation.
    Clinical • P1 data • Journal • Combination therapy • Metastases
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    IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • TLR9 (Toll Like Receptor 9) • CXCR1 (Chemokine (C-X-C motif) receptor 1)
    |
    Opdivo (nivolumab) • pixatimod (PG545)
    over2years
    Pixatimod (PG545) Plus Nivolumab in PD-1 Relapsed/Refractory Metastatic Melanoma and NSCLC and With Nivolumab and Low-dose Cyclophosphamide in MSS Metastatic Colorectal Carcinoma (mCRC) (clinicaltrials.gov)
    P2a, N=61, Recruiting, Diwakar Davar | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy • IO biomarker • Pan tumor
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    KRAS mutation • EGFR mutation • BRAF mutation • KRAS wild-type • RAS wild-type
    |
    Opdivo (nivolumab) • cyclophosphamide • pixatimod (PG545)
    over2years
    Pixatimod (PG545) Plus Nivolumab in PD-1 Relapsed/Refractory Metastatic Melanoma and NSCLC and With Nivolumab and Low-dose Cyclophosphamide in MSS Metastatic Colorectal Carcinoma (mCRC) (clinicaltrials.gov)
    P2a, N=61, Not yet recruiting, Diwakar Davar
    New P2a trial • Combination therapy • IO biomarker • Pan tumor
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    KRAS mutation • EGFR mutation • BRAF mutation
    |
    Opdivo (nivolumab) • cyclophosphamide • pixatimod (PG545)
    3years
    [VIRTUAL] Synergistic cytotoxic effect of sulfated glycolipid PG545 in combination with ATR inhibition in ovarian cancer cells (AACR 2021)
    Proliferation and clonogenic assay showed that combination of PG545 with ATR shRNA or ATR inhibitor (ATRi; VE-822) synergistically decreased cell survival compared with single-agent treatments in two OC cell lines, OVCAR5 and OVCAR8 cells. Moreover, ATRi diminished the cell cycle effects of PG545 and markedly enhanced PG545-induced apoptosis in OC cell lines. Taken together, our results indicate that the combination of PG545 with ATR inhibition may be promising options to be considered in future clinical trials of OC.
    Combination therapy
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    CHEK1 (Checkpoint kinase 1)
    |
    berzosertib (M6620) • pixatimod (PG545)
    over3years
    Sulfated glycolipid PG545 induces endoplasmic reticulum stress and augments autophagic flux by enhancing anticancer chemotherapy efficacy in endometrial cancer. (PubMed, Biochem Pharmacol)
    PG545 exhibited strong synergy as assessed by the Chou-Talalay-Method in vitro when combined with cisplatin, or paclitaxel in both type I (Hec1B) and type II (ARK2) EC cell lines. Collectively these data indicate that PG545 exhibits strong synergistic effects with chemotherapeutics in vitro and showed promising antitumor activity in vivo. Our preclinical data indicates that in future studies PG545 can be a useful adjunct to chemotherapy in endometrial cancer.
    Clinical • Journal
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    FGF2 (Fibroblast Growth Factor 2) • EGF (Epidermal growth factor)
    |
    cisplatin • paclitaxel • pixatimod (PG545)