The European Commission has granted conditional marketing authorisation for Polivy ( Polatuzumab vedotin ), in combination with Bendamustine plus MabThera ( Rituximab ) ( BR ), for the treatment of adult patients with relapsed or refractory ( R/R ) diffuse large B-cell lymphoma ( DLBCL ) who are not candidates for a haematopoietic stem cell transplant.
The conditional approval is based on the results from the phase Ib/II GO29365 study, the first and only clinical trial to show higher response rates and improved overall survival ( OS ) compared to BR regimen, in people with R/R DLBCL who are not candidates for a haematopoietic stem cell transplant.
Results of the study have shown that 40% of people treated with Polivy plus BR regimen achieved a complete response ( n=16/40 ), meaning no cancer could be detected at the time of assessment, compared to 17.5% ( n=7/40 ) with BR regimen alone.
Complete response rates were assessed by an independent review committee.
The study has also shown that overall survival more than doubled, with a median of 12.4 months in the Polivy arm versus 4.7 months in the BR regimen alone arm ( hazard ratio, HR=0.42 ).
Furthermore, patients treated with Polivy plus BR regimen showed a longer time between first response to treatment and disease worsening than those receiving BR regimen alone ( investigator assessed median duration of response: 10.3 months vs. 4.1 months; HR=0.44 ). <
The most commonly reported adverse events in people treated with Polivy in combination with BR regimen included anaemia, thrombocytopenia, neutropenia, fatigue, diarrhoea, nausea, and pyrexia.
Conditional approval is granted to a medicinal product that fulfils an unmet medical need where the benefit of immediate availability outweighs the risk of less comprehensive data than normally required.
Conditional EU approval follows the US Food and Drug Administration’s ( FDA ) accelerated approval of Polivy in combination with BR regimen for the treatment of people with R/R DLBCL who have received at least two prior therapies, in June 2019.
Polivy was granted Breakthrough Therapy Designation by the FDA and PRIME ( PRIority MEdicines ) designation by the European Medicines Agency ( EMA ) for the treatment of people with R/R DLBCL in 2017.
GO29365 was a global, phase Ib/II study evaluating the safety, tolerability and activity of Polatuzumab vedotin in combination with Bendamustine and Rituximab or Obinutuzumab ( Gazyvaro ) in relapsed or refractory follicular lymphoma or diffuse large B-cell lymphoma. Eligible patients were not candidates for a haematopoietic stem cell transplant at study entry.
The phase II part of the study randomised 80 patients with heavily pre-treated R/R DLBCL to receive either BR regimen, or BR regimen in combination with Polatuzumab vedotin for a fixed duration of six 21-day cycles.
Of the patients enrolled, 80% had refractory disease.
The primary endpoint was complete response ( CR ) at the end of treatment, as measured by positron emission tomography and assessed by an independent review committee ( IRC ). Secondary endpoints included overall response rate ( ORR; CR and partial response ) by investigator assessment and best ORR at the end of treatment by investigator and IRC assessment. Exploratory endpoints included duration of response, progression-free survival, event-free survival and overall survival.
Polatuzumab vedotin is a first-in-class anti-CD79b antibody-drug conjugate ( ADC ). The CD79b protein is expressed specifically in the majority of B-cells ( an immune cell impacted in some types of non-Hodgkin lymphoma [ NHL] ), making it a promising target for the development of new therapies.
Polatuzumab binds to CD79b and destroys these B-cells through the delivery of an anti-cancer agent ( Monomethyl Auristatin E; MMAE, Vedotin ), which is thought to minimise the effects on normal cells.
Diffuse large B-cell lymphoma is the most common form of non-Hodgkin lymphoma, accounting for about one in three cases of NHL.
DLBCL is an aggressive type of NHL, which is generally responsive to treatment in the frontline.
However, as many as 40% of patients will relapse, at which time salvage therapy options are limited and survival is short.
Approximately 150,000 people worldwide are estimated to be diagnosed with DLBCL each year. ( Xagena )
Source: Roche, 2020