Polatuzumab Vedotin Shows Promise Among Previously Treated DLBCL Patients
Results of the GO29365 study showed that polatuzumab vedotin in combination with bendamustine plus rituximab (BR) improved median overall survival compared to BR alone (12.4 vs. 4.7 months, HR=0.42; 95% CI 0.24-0.75), in people with R/R diffuse large B-cell lymphoma (DLBCL) not eligible for a hematopoietic stem cell transplant.
The study also showed that 40 percent of people treated with polatuzumab vedotin plus BR achieved a complete response (CR), while only 18 percent of people treated with BR alone achieved a CR.
GO29365 is a global, phase Ib/II randomized study evaluating the safety, tolerability, and activity of polatuzumab vedotin in combination with bendamustine and rituximab or obinutuzumab in relapsed or refractory (R/R) DLBCL or follicular lymphoma.
The phase II stage randomized 80 patients with heavily pre-treated R/R DLBCL to receive either BR, or BR in combination with polatuzumab vedotin. Patients enrolled had received a median of two prior therapies (a range of 1-7 prior therapies in the polatuzumab vedotin arm and range of 1-5 prior therapies in the BR alone arm).
The primary endpoint was CR at the end of treatment, as measured by PET and assessed by an independent review committee (IRC). Secondary endpoints included objective response (OR; CR and partial response) by investigator assessment and best objective response at the end of treatment by investigator and IRC assessment. Exploratory endpoints included duration of response (DOR), progression-free survival (PFS), event-free survival, and overall survival (OS).
Forty percent of people treated with polatuzumab vedotin plus BR achieved a CR while only 18 percent of people treated with BR alone achieved a CR. Polatuzumab vedotin in combination with BR showed a median OS of over 1 year compared to the BR arm (12.4 vs. 4.7 months; HR=0.42; 95% CI 0.24-0.75) in people with R/R DLBCL not eligible for a hematopoietic stem cell transplant.
Polatuzumab vedotin plus BR increased median PFS and led to a 66 percent reduction in risk of disease worsening or death compared to BR alone (median PFS: 7.6 months vs. 2.0 months; HR=0.34; 95% CI 0.20-0.57).
Patients treated with polatuzumab vedotin plus BR showed a longer time between first response to treatment and disease worsening than those receiving BR alone (investigator assessed median DOR: 10.3 months vs. 4.1 months; HR=0.44).
Updated safety results are similar to those previously described, with infections and cytopenias remaining the most common grade 3-4 adverse events. Polatuzumab vedotin plus BR had higher rates of grade 3-4 cytopenias compared to BR; however, infection, and transfusion rates remained similar between arms.
Polatuzumab vedotin is a first-in-class anti-CD79b antibody drug conjugate (ADC) currently being investigated for the treatment of several types of non-Hodgkin lymphoma (NHL). The CD79b protein is highly specific and expressed in the majority of types of B-cell NHL, making it a promising target for the development of new therapies. Polatuzumab vedotin binds to CD79b and destroys these B cells through a targeted approach, which is thought to minimize the effects on normal cells while maximizing tumor cell death.
Based on findings from the GO29365 study, the FDA has accepted the Biologics License Application (BLA) and granted Priority Review for polatuzumab vedotin in combination with BR for the treatment of people with R/R DLBCL. The FDA is expected to make a decision on approval by Aug. 19, 2019.
Priority Review designation is granted to medicines that the FDA considers to have the potential to provide significant improvements in the safety and effectiveness of the treatment, prevention, or diagnosis of a serious disease.
Polatuzumab vedotin was also granted Breakthrough Therapy Designation by the FDA and PRIME (PRIority MEdicines) designation by the European Medicines Agency for the treatment of people with R/R DLBCL in 2017. Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat a serious condition with preliminary evidence that indicates they may demonstrate substantial improvement over existing therapies.