The U.S. Food and Drug Administration has granted priority review to Roche‘s polatuzumab vedotin in combination with Rituxan (rituximab) and the chemotherapy bendamustine for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
The FDA is expected to make a decision on whether to approve the treatment combination by Aug. 19.
“We are working with the FDA to bring this important new option to patients with this aggressive disease as quickly as possible,” Sandra Horning, MD, chief medical officer and head of global product development at Roche, said in a press release.
The biologics license application was based on results from the global Phase 1b/2 GO29365 trial (NCT02257567), which included heavily pretreated follicular lymphoma and DLBCL patients who were not eligible for a stem cell transplant.
The trial was meant to determine if adding polatuzumab vedotin to a combination of bendamustine and Rituxan (by Biogen and Genentech) or bendamustine and Gazyva (obinutuzumab, by Roche-owned Genentech), was safe, well-tolerated, and effective in these patients.
The trial’s Phase 2 part included 80 pre-treated DLBCL patients (median of two prior therapies), who randomly received polatuzumab vedotin plus Rituxan and bedamustine, or Rituxan and bendamustine only. The study’s primary goal was complete response, or the disappearance of all cancer signs, at the end of treatment.
Secondary goals included objective response — complete and partial responses — and best objective response at the end of treatment, as evaluated by both the investigators and an independent review committee. Other exploratory goals were duration of response, progression-free survival (PFS; the time patients live without cancer progression), event-free survival, and overall survival.
Adding polatuzumab vedotin to Rituxan and bendamustine extended the patients’ median overall survival from 4.7 months to more than one year (12.4 months). Additionally, 40% of participants treated with the triple therapy achieved a complete response, compared with only 18% of patients receiving Rituxan and bendamustine alone.
The triple treatment also increased median PFS from two to 7.6 months and reduced the risk of disease worsening or death by 66% compared with Rituxan and bedamustine alone.
Patients on polatuzumab vedotin demonstrated longer responses — 10.3 months vs. 4.1 months.
Updated safety data are similar to those previously reported, with infections and reduced numbers of blood cells remaining the most common severe to life-threatening adverse events. Although the triple therapy had higher rates of severely low blood cell numbers, infection and transfusion rates were similar between the two groups.
Polatuzumab vedotin is an antibody-drug conjugate that targets the CD79b protein — a cell surface molecule found in most types of B-cell non-Hodgkin’s lymphoma. The binding of polatuzumab vedotin to CD79b is intended to kill these B-cells with a targeted approach to minimize the effects on healthy cells while boosting tumor cell death.
The potential medication had already been granted breakthrough therapy designation by the FDA and priority medicines, or PRIME, designation by the European Medicines Agency.
