FDA Accepts sBLA for Genentech’s Polivy Combination for Diffuse Large B-Cell Lymphoma

The FDA has accepted a supplemental biologics license application (sBLA) for polatuzumab vedotin-piiq (Polivy; Genentech) in combination with rituximab (Rituxan; Genentech) and cyclophosphamide, doxorubicin, and prednisone (R-CHP) for the treatment of individuals with previously untreated diffuse large B-cell lymphoma (DLBCL).

The FDA is expected to make a decision on the approval by April 2, 2023.

“The POLARIX study results suggest that [polatuzumab vedotin-piiq] plus R-CHP could transform the treatment of this aggressive malignancy, and we are working with the FDA to bring this combination to newly diagnosed DLBCL patients as soon as possible,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, said in a statement. “We hope it will become the new standard of care for the first-line treatment of DLBCL, potentially reducing the need for subsequent treatments and limiting patient burden.”

The sBLA is based on results from the phase 3 POLARIX study, which is the first in 2 decades to show a clinically meaningful improvement in progression-free survival (PFS) compared with the standard of care, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), according to the statement.

The risk of death, disease progression, or relapse was reduced by 27% with polatuzumab vedotin-piiq plus R-CHP compared with R-CHOP, after a median follow-up of 28.2 months.

Investigators reported that the safety outcomes were consistent with those seen in previous clinical trials and the safety profile was comparable between the 2 regimens.

The reports of grade 3 and 4 adverse events (AEs) were similar between polatuzumab vedotin-piiq plus R-CHP and R-CHOP at 57.7% and 57.5%, respectively. Serious AEs were also similar at 34% and 30.6%, and grade 5 AEs were also similar at 3% and 2.3%, respectively. AEs leading to dose reduction were 9.2% and 13%, respectively.

The study included 879 individuals who were randomized 1 to 1 to receive either polatuzumab vedotin-piiq plus R-CHP, plus a vincristine placebo for 6 cycles, followed by rituximab for 2 cycles, or R-CHOP, plus a polatuzumab vedotin-piiq placebo for 6 cycles, followed by 2 cycles of rituximab.

The primary outcome was PFS, which was assessed using the Lugano Response Criteria for malignant lymphoma.

Based on pivotal data from the POLARIX study, the European Commission approved polatuzumab vedotin-piiq plus R-CHP in May 2022 for the treatment of adult individuals with previously untreated DLBCL.

The medication is approved as a readily available, fixed-duration treatment option for relapsed or refractory DLBCL in combination with bendamustine and Rituxan/Mebthera in more than 70 countries, including the European Union and the United States.

Genentech continues to explore areas of unmet need where polatuzumab vedotin-piiq could potentially provide additional benefits. This includes ongoing studies investigating combinations of polatuzumab vedotin-piiq with the mosunetuzumab and glofitamab, Genentech’s CD20xCD3 T-cell engaging bispecific antibodies, and with rituximab in combination with gemcitabine and oxaliplatin in the phase 3 POLARGO study.

Reference

FDA accepts supplemental biologics license application for Genentech’s Polivy combination for people with previously untreated diffuse large B-cell lymphoma. News release. Genentech. August 15, 2022. Accessed August 17, 2022. https://www.gene.com/media/press-releases/14965/2022-08-15/fda-accepts-supplemental-biologics-licen