0QQ6 Roche Holding Ag

Five-year results confirm Roche’s Polivy combination therapy as new standard of care for previously untreated aggressive lymphoma

• Exploratory long-term follow-up analysis of the phase III POLARIX study indicated a positive trend in overall survival in favour of Polivy in combination with R-CHP for people with first-line diffuse large B-cell lymphoma (DLBCL)¹
• Patients treated with Polivy in combination with R-CHP required fewer subsequent treatments, potentially reducing burdens on patients and healthcare systems¹
• These encouraging five-year results continue to highlight the potential of this Polivy combination to improve outcomes in first-line DLBCL, an area that previously had little advancement in nearly two decades

Basel, 8 December 2024 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today data from a five-year follow-up of the pivotal phase III POLARIX study evaluating Polivy® (polatuzumab vedotin) in combination with MabThera®/Rituxan® (rituximab), cyclophosphamide, doxorubicin and prednisone (R-CHP) in people with untreated diffuse large B-cell lymphoma (DLBCL). Data were presented in an oral session at the 66^th American Society of Hematology (ASH) Annual Meeting and Exposition, 7-10 December 2024 in San Diego, US. This latest analysis conducted after a median follow-up of 60.9 months, includes descriptive data on primary and secondary endpoints, as well as safety results.¹

“POLARIX was the first trial to elevate treatment standards for frontline diffuse large B-cell lymphoma in 20 years and we are additionally encouraged by the five-year follow-up results,” said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. “More than 38,000 people worldwide have been treated with Polivy in combination with R-CHP and these data continue to underscore its potential to improve outcomes for people diagnosed with this aggressive lymphoma.”

Follow-up exploratory analysis after five-years indicated a positive trend in overall survival (OS) in the intent-to-treat (ITT) population in favour of Polivy in combination with R-CHP compared to MabThera/Rituxan plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Results showed a trend in reduction in the risk of death (HR 0.85; 95% CI: 0.63–1.15) for people with previously untreated DLBCL with the Polivy combination, an improvement on the three-year follow-up data (HR 0.94; 95% CI: 0.67–1.33). The five-year analysis of POLARIX indicates that the full difference in OS between treatment arms has yet to be observed and an additional two years of follow-up will continue.¹

“Diffuse large B-cell lymphoma is a notoriously challenging cancer to treat, however, Polivy in combination with R-CHP has shown to be a critical advance for patients by helping to reduce relapse and disease progression,” said Gilles Salles, MD, PhD, Chief of Lymphoma Service, Division of Hematological Malignancies, Memorial Sloan Kettering Cancer Center, US. “The survival trend seen in this follow-up analysis reinforces the potential impact of frontline treatment with Polivy in combination with R-CHP and its role as a standard of care therapy.”

In addition to the positive trend in OS, an observational analysis suggested nearly 25% fewer follow-up treatments such as radiation, systemic chemotherapy and CAR-T cell therapy were needed in patients receiving Polivy in combination with R-CHP compared to those treated with R-CHOP (38.3% vs 61.7%).¹ Based on findings from a previous economic analysis which found that total healthcare costs increased with each additional line of treatment in relapsed or refractory DLBCL, a reduction in the number of subsequent therapies could potentially alleviate some of the burdens associated with relapse and disease progression.²

At five years of follow-up, benefits in progression-free survival and disease-free survival with Polivy in combination with R-CHP were maintained, consistent with the three-year follow-up data, reinforcing the potential of Polivy in combination with R-CHP to provide durable and lasting remissions. The latest follow-up data also showed a numerical reduction in death related to patients’ lymphoma in those treated with Polivy in combination with R-CHP compared to those treated with R-CHOP (9.0% vs 11.4%). The safety profile remains consistent with the known profiles of the individual study medicines with no new safety signals observed, reinforcing the positive benefit-risk profile of this Polivy combination.¹

Results from an expanded cohort of 1,000 patients including global and Chinese patients demonstrated comparability to the global ITT population.¹

Polivy in combination with R-CHP is currently approved for the treatment of first-line (1L) DLBCL in more than 90 countries worldwide including the US, countries throughout the EU, the UK, Japan, Canada and China. Roche continues to work with health authorities around the world to bring this treatment regimen to even more patients.

Roche aims to offer various treatment options for DLBCL that meet the diverse needs of patients and healthcare systems. In an effort to elevate treatment standards even further, Roche is exploring Polivy in combination with other molecules including its bispecific antibodies. Studies include the phase III SUNMO trial evaluating the efficacy and safety of subcutaneously administered Lunsumio® (mosunetuzumab) in combination with intravenous (IV) Polivy versus IV MabThera/Rituxan plus gemcitabine and oxaliplatin (R-GemOx) in second-line or later DLBCL, and the phase III SKYGLO trial investigating the efficacy of Polivy in combination with R-CHP and Columvi® (glofitamab) versus Polivy in combination with R-CHP in 1L DLBCL.

About the POLARIX study
POLARIX [NCT03274492] is an international phase III, randomised, double-blind, placebo-controlled study evaluating the efficacy, safety and pharmacokinetics of Polivy® (polatuzumab vedotin) plus MabThera®/Rituxan® (rituximab), cyclophosphamide, doxorubicin, and prednisone (R-CHP) versus rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in people with previously untreated diffuse large B-cell lymphoma (DLBCL). Eight-hundred and seventy-nine patients were randomised 1:1 to receive either Polivy plus R-CHP plus a vincristine placebo for six cycles, followed by MabThera/Rituxan for two cycles; or R-CHOP plus a Polivy placebo for six cycles, followed by two cycles of MabThera/Rituxan. The primary outcome measure is progression-free survival (PFS) as assessed by the investigator using the Lugano Response Criteria for malignant lymphoma.  PFS is a clinically meaningful disease-related outcome for patients with previously untreated DLBCL as it represents the goal of first-line therapy: decreasing the risk of disease worsening. Overall survival is a secondary endpoint in the POLARIX study.

About diffuse large B-cell lymphoma (DLBCL)
DLBCL is the most common form of non-Hodgkin lymphoma (NHL), accounting for about one in three cases of NHL.³ DLBCL is an aggressive (fast-growing) type of NHL. While it is generally responsive to treatment in the frontline, as many as 40% of people will relapse or have refractory disease, at which time salvage therapy options are limited and survival is short. ^4,5 Improving treatments earlier in the course of the disease and providing much needed alternative options could help to improve long-term outcomes. Approximately 160,000 people worldwide are estimated to be diagnosed with DLBCL each year.^1,6

About Polivy® (polatuzumab vedotin)
Polivy 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. Polivy binds to cancer cells such as CD79b and destroys these B-cells through the delivery of an anti-cancer agent, which is thought to minimise the effects on normal cells. Polivy is being developed by Roche using Pfizer ADC technology and is currently being investigated for the treatment of several types of NHL.

About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for more than 25 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera/Rituxan, Gazyva®/Gazyvaro® (obinutuzumab), Polivy, Venclexta®/Venclyxto® (venetoclax) in collaboration with AbbVie, Hemlibra® (emicizumab), PiaSky® (crovalimab), Lunsumio® (mosunetuzumab) and Columvi® (glofitamab). Our pipeline of investigational haematology medicines includes T-cell engaging bispecific antibody cevostamab, targeting both FcRH5 and CD3 and Tecentriq® (atezolizumab). Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further.

About Roche
Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice.
For over 125 years, sustainability has been an integral part of Roche’s business. As a science-driven company, our greatest contribution to society is developing innovative medicines and diagnostics that help people live healthier lives. Roche is committed to the Science Based Targets initiative and the Sustainable Markets Initiative to achieve net zero by 2045. 

Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. 

For more information, please visit www.roche.com.

All trademarks used or mentioned in this release are protected by law.

References
[1] Gilles S, et al. Five-Year Analysis of the POLARIX Study: Prolonged Follow-up Confirms Positive Impact of Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (Pola-R-CHP) on Outcomes. Presented at: ASH Annual Meeting and Exposition; 2024 Dec 7-10; San Diego, CA, USA. Abstract #469.
[2] Gatwood J, et al. Total cost of care in Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL). Presented at: ASH Annual Meeting and Exposition; 2022, Dec 10-13. Abstract #3527
[3]  Cancer.Net. Lymphoma - Non-Hodgkin: Subtypes. [Internet; cited December 2024]. Available from: https://www.cancer.net/cancer-types/lymphoma-non-hodgkin/subtypes
[4] Sehn LH, et al. Diffuse Large B-Cell Lymphoma. N Engl J Med. 2021;384(9):842-858.
[5] Maurer MJ, et al. Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy. J Clin Oncol. 2014;32:1066-73.
[6] World Health Organization. Numbers derived from GLOBOCAN 2022. Non-Hodgkin Lymphoma Factsheet [Internet; cited December 2024]. Available from: https://gco.iarc.who.int/media/globocan/factsheets/cancers/34-non-hodgkin-lymphoma-fact-sheet.pd.

Dr. Salles has financial interests related to Roche and Genentech.

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