Polivy (polatuzumab vedotin-piiq)

P2, N=60, Not yet recruiting, Beth Israel Deaconess Medical Center

Among 24 patients with recurrent tumor biopsies, 13% showed loss of/decreased CD79B expression. In conclusion, immunohistochemical CD79B expression was not significantly associated with PV-containing therapy efficacy, which remained effective even in DLBCL with low CD79B expression.

The patient was treated with Pola-R-CHP followed by CNS-directed therapy, including high-dose methotrexate and intrathecal chemotherapy...Tumor-associated RANKL expression may be associated with the osteolytic features observed in this case. Early biopsy and systemic evaluation of cutaneous lesions are essential, as they may reflect aggressive systemic disease.

For many years, R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) has been the standard first-line treatment for DLBCL; however, pola-R-CHP (polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone) has recently emerged as a new treatment option...In addition, agents that have demonstrated efficacy in patients with relapsed or refractory DLBCL-such as the anti-CD19 antibody tafasitamab and immunomodulatory drugs such as golcadomide-are currently under investigation for use in newly diagnosed patients...BsAbs can enable more flexible treatment strategies, including combination regimens with cytotoxic or chemotherapy-free approaches. This review summarizes recent advances and ongoing trials that are investigating novel therapeutic strategies for newly diagnosed DLBCL that may soon be incorporated into clinical practice.

P3, N=306, Completed, GWT-TUD GmbH | Active, not recruiting --> Completed

P2, N=138, Not yet recruiting, SWOG Cancer Research Network

P1/2, N=40, Not yet recruiting, Ruijin Hospital

POLA demonstrated robust single-agent antitumor activity in vivo, including in PDX models derived from patients with ibrutinib-resistant MCL. This signature likely reflects core pathways associated with POLA resistance and highlights potential novel therapeutic vulnerabilities. These findings strongly support further clinical investigation of POLA in combination with VEN as a BCL2- and MCL1-targeting therapeutic strategy in patients with R/R MCL and BCL2-positive R/R DLBCL.

P1, N=34, Active, not recruiting, National Cancer Institute (NCI) | N=55 --> 34 | Recruiting --> Active, not recruiting

P2, N=35, Recruiting, The First Affiliated Hospital with Nanjing Medical University

P2, N=178, Not yet recruiting, Ruijin Hospital

Previous studies have shown that the combination of the second-generation BTKi zanubrutinib and polatuzumab vedotin, within the R-CHOP regimen, yielded higher response rates in preliminary clinical studies; however, the efficacy of this combination remains unclear. Notably, the combination showed superior synergistic efficacy in GCB-subtype cells. In conclusion, these findings provide a novel mechanistic rationale for combining zanubrutinib and polatuzumab vedotin in DLBCL treatment, regardless of cell-of-origin subtype.