Roche's CD79b-Targeted Antibody-Drug Conjugate Polivy Plus Bendamustine and Rituximab Achieves 42.5% Complete Response Rate at 4 Years in Relapsed/Refractory DLBCL

December 09, 2020 News /BioValleyBIOON/ -- Roche recently presented long-term data from the pivotal Phase Ib/II GO29365 study at the 62nd Annual Meeting of the American Society of Hematology (ASH), including data from a single-arm expansion cohort comprising an additional 106 patients. The results showed: in patients ineligibleStem CellsIn patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who have undergone transplantation, the CD79b-targeted antibody-drug conjugate (ADC) Polivy (polatuzumab vedotin) in combination with bendamustine and MabThera/Rituxan (MabThera; generic name: rituximab) (hereinafter referred to as BR) has demonstrated therapeutic benefits.

Polivy is a first-in-class antibody-drug conjugate (ADC) targeting CD79b. Based on the preliminary results of the GO29365 study, the drug was approved in the United States in June 2019FDAAccelerated approval, in combination with bendamustine and rituximab (hereinafter referred to as BR therapy), for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) who have received at least two prior therapies; in the European Union, the drug received conditional approval in January 2020, in combination with BR therapy, for the treatment of patients ineligible for hematopoieticStem Cellspatients with relapsed/refractory (R/R) DLBCL who have undergone transplantation. In the United States and the European Union, Polivy has been granted orphan drug designation for the treatment of DLBCL, as well as Breakthrough Therapy Designation (BTD) and Priority Medicines (PRIME) status, respectively.

It is worth noting that Polivy is the first immunochemotherapy approved for the treatment of relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). Compared with the commonly used regimen (BR), Polivy in combination with BR significantly improves clinical outcomes for patients. DLBCL is an aggressive hematologic malignancy, and each recurrence typically makes the disease more difficult to treat. Approximately 40% of previously untreated DLBCL patients experience relapse after standard therapy, leaving limited subsequent treatment options. Polivy will provide an important therapeutic option for these patients.

At the ASH Annual Meeting, the latest data from the randomized cohort (n=80) showed that,With longer follow-up (48.9 months), the complete response (CR) rate among patients who completed Polivy+BR treatment was 42.5% (n=17/40), compared to 17.5% (n=7/40) in patients receiving BR alone, indicating that the Polivy+BR regimen can provide durable responses.No new or delayed safety signals were reported. The latest data from the expansion cohort showed a complete response (CR) rate of 38.7% (n=41/106) in patients treated with the Polivy+BR regimen. These findings further support that Polivy-based combination therapies can provide clinical benefits for patients with this aggressive disease.

Additional data from the randomized cohort also indicate that the survival benefit of the Polivy + BR regimen persists with longer follow-up. After a median follow-up of 48.9 months, the median progression-free survival (PFS) assessed by an independent review committee was 9.2 months in the Polivy + BR group versus 3.7 months in the BR group. The median overall survival (OS) remained at 12.4 months in the Polivy + BR group, compared with 4.7 months in the BR group.

New data from the expanded cohort (including 37 patients with second-line DLBCL) were consistent with the previously reported results of the GO29365 study and demonstrated the efficacy of the Polivy + BR regimen across a broad patient population. Patients treated with Polivy + BR had a median PFS of 6.6 months and a median OS of 12.5 months. Subgroup analyses of this cohort further indicated that Polivy + BR was effective across different patient populations, including high-risk patients, regardless of prior lines of therapy: the median OS was 7.6 months in the primary refractory subgroup (n=55) versus 32 months in the non-primary refractory subgroup (n=97).

Diffuse large B-cell lymphoma (DLBCL) is a histological subtype of non-Hodgkin lymphoma (NHL) and is classified as an aggressive disease. DLBCL is the most common type of NHL, accounting for 30–40% of all NHL cases. It frequently occurs in middle-aged and elderly individuals, predominantly affecting those over the age of 60. It has been reported that this diseaseDiagnosisThe median age was 64 years. Rituximab combined with chemotherapy is the standard first-line regimen for diffuse large B-cell lymphoma (DLBCL); however, approximately 40% of patients experience relapse due to inadequate treatment response. Despite autologousStem CellsAutologous stem cell transplantation (ASCT) is recommended for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL); however, approximately half of these patients are ineligible for ASCT due to failure of salvage chemotherapy prior to transplantation. Furthermore, there is currently no standard treatment regimen established for patients who are ineligible for ASCT due to factors such as advanced age or comorbidities. Therefore, there is an urgent need for more effective novel therapeutic options for relapsed or refractory DLBCL.

Polivy was developed by Genentech, a member of the Roche Group, using SeattleGeneticsThe company is developing ADC technology, a first-in-class ADC specifically targeting CD79b. It consists of a humanized anti-CD79b antibody conjugated to the anti-mitotic agent MMAE (monomethyl auristatin E) and is currently being developed for the treatment of several types of non-Hodgkin lymphoma (NHL). CD79b is highly specifically expressed in most types of B-cell NHL, making it a promising target for the development of new therapies. Polatuzumab vedotin targets and binds to CD79b, disrupting these B cells while maximizing damage to cancer cells and minimizing impact on normal cells.

In addition to relapsed/refractory (R/R) disease, Polivy is also being investigated in the first-line treatment of diffuse large B-cell lymphoma (DLBCL), with Phase III POLARIX trial data expected in 2021. Other ongoing studies include combination regimens of Polivy with Gazyva/Gazyvaro (obinutuzumab), Venclexta/Venclyxto (venetoclax), and the CD20xCD3 bispecific antibodies mosunetuzumab and glofitamab, to determine the potential of Polivy to deliver clinical benefits in areas with unmet medical needs. (Bioon.com)

Original source: New data presented at ASH 2020 reinforces the benefit/risk profile of fixed-duration Polivy plus bendamustine and MabThera/Rituxan in patients with relapsed or refractory diffuse large B-cell lymphoma