• Polivy plus R-CHP has been approved as a new treatment option, the first in 20 years, for untreated diffuse large B-cell lymphoma (DLBCL) following the approval for relapsed or refractory DLBCL last year
• The new Polivy plus R-CHP regimen demonstrated improvement in progression free survival (PFS) compared to standard of care R-CHOP regimen in previously untreated DLBCL
• The approval is based on the results from a Phase III POLARIX study in patients with previously untreated DLBCL

TOKYO, August 24, 2022 -- Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) announced that it obtained regulatory approval today from the Ministry of Health, Labour and Welfare for the anticancer agent/antimicrotubule binding anti-CD79b monoclonal antibody Polivy^® intravenous infusion 30 mg and 140 mg [generic name: polatuzumab vedotin (genetical recombination)] for an additional indication of treatment of patients with previously untreated diffuse large B-cell lymphoma (DLBCL).

“We are very pleased to be able to offer the first new treatment in 20 years to patients with previously untreated diffuse large B-cell lymphoma (DLBCL) through this line extension approval,” said Chugai’s President and CEO Dr. Osamu Okuda. “Based on our long experience and expertise in hematological cancer, we will continue to provide information on the proper use of Polivy for the benefit of patients with untreated DLBCL, as well as those with relapsed or refractory DLBCL.”

Polivy is an antibody-drug conjugate, which is a combination of an antibody and a small molecule compound. This approval is based on the global phase III clinical study (POLARIX study) in patients with previously untreated DLBCL. The study, which Japan participated in, is a phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy, safety and pharmacokinetics of Polivy plus R-CHP versus R-CHOP. 879 patients were enrolled, and the primary endpoint was progression-free survival (PFS) as assessed by the investigator using the Lugano Response Criteria for malignant lymphoma.

As a leading company in the field of oncology in Japan, Chugai is committed to contribute to patients and medical professionals through offering innovative drugs to fulfill unmet medical needs in cancer treatment.

Approval Information *Changes are underlined.

Indication:
Diffuse large B-cell lymphoma

Dosage and administration:
The usual adult dosage is 1.8 mg/kg (body weight) polatuzumab vedotin (genetical recombination) administered by intravenous infusion every 3 weeks for 6 doses, in combination with the antineoplastic agents given below. Administer the first infusion over 90 minutes. If the first infusion is well tolerated, subsequent infusions may be administered over a shorter time of at least 30 minutes. Reduce the dose as necessary in accordance with the patient’s condition.

• Administration in combination with rituximab (genetical recombination), cyclophosphamide hydrate, doxorubicin hydrochloride, and prednisolone or methylprednisolone
• Administration in combination with bendamustine hydrochloride preparation and rituximab (genetical recombination)

[Reference Information]
Chugai Files for Additional Indication of Polivy for Previously Untreated Diffuse Large B-cell Lymphoma (Press release issued on December 10, 2021)
https://www.chugai-pharm.co.jp/english/news/detail/20211210170000_880.html

Roche’s Polivy combination reduced the risk of disease worsening or death by 27% in people with previously untreated aggressive form of lymphoma (Press release issued by Roche on December 14, 2021)
https://www.roche.com/media/releases/med-cor-2021-12-14

About Polivy (polatuzumab vedotin)
Polatuzumab vedotin was developed by Roche using Seagens’ ADC technology. It is a first-in-class anti-CD79b antibody-drug conjugate (ADC), comprising the anti-CD79b humanized monoclonal antibody and a tubulin polymerization inhibitor attached together using a linker. The CD79b protein is expressed specifically in the majority of B-cells, making it a promising target for the development of new therapies.^{1, 2)} Polatuzumab vedotin binds to CD79b and destroys these B-cells through the delivery of an anti-cancer agent, which is thought to suppress the effects on normal cells.^{3, 4)} Polatuzumab vedotin was granted accelerated approval in the US in June 2019 and conditional marketing authorization in the EU in January 2020, respectively.

About POLARIX study
POLARIX (NCT03274492) is an international phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy, safety and pharmacokinetics of Polivy plus Rituxan^® (rituximab), cyclophosphamide, doxorubicin and prednisone (R-CHP) versus Rituxan, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in people with previously untreated diffuse large B-cell lymphoma (DLBCL). 879 patients were randomized 1:1 to receive either Polivy plus R-CHP plus a vincristine placebo for six cycles, followed by Rituxan for two cycles; or R-CHOP plus a Polivy placebo for six cycles, followed by two cycles of Rituxan.

The primary outcome measure is progression-free survival as assessed by the investigator using the Lugano Response Criteria for malignant lymphoma.
Data from the pivotal phase III POLARIX study showed a significant improvement in PFS with Polivy plus R-CHP versus R-CHOP in patients with previously untreated DLBCL after a median follow-up of 28.2 months (hazard ratio [HR] 0.73; 95% CI: 0.57–0.95; P<0.02).The safety profile was comparable for Polivy plus R-CHP versus R-CHOP, including rates of grade 3-4 adverse events (AEs; 57.7% versus 57.5%), serious AEs (34.0% versus 30.6%), grade 5 AEs (3.0% versus 2.3%), and AEs leading to dose reduction (9.2% versus 13.0%), respectively.⁵⁾

POLARIX is being conducted in collaboration with The Lymphoma Study Association (LYSA) and The Lymphoma Academic Research Organisation (LYSARC).

About the LYSA and the LYSARC
The Lymphoma Study Association, or LYSA, is the internationally leading cooperative group for lymphoma research in Europe, conducting clinical studies ranging from the first tests of new medicines in humans to the establishment of reference therapeutic strategies. LYSA includes in its network more than 120 care centers distributed throughout three countries (France, Belgium, Portugal), and collaborates with many scientific teams at the international level.
The Lymphoma Academic Research Organisation, or LYSARC, is the LYSA operational structure that conducts clinical research projects on lymphomas at the international level.

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.⁶⁾ DLBCL is an aggressive type of NHL.⁷⁾ While it is generally responsive to treatment in the frontline, as many as 40% of patients will relapse or have refractory disease, at which time salvage therapy options are limited and survival is short.⁷⁾ Approximately 150,000 people worldwide are estimated to be diagnosed with DLBCL each year.⁸⁾

Salvage therapy: Salvage chemotherapy or salvage therapy is used to treat patients with hematologic malignancy who experienced no therapeutic effects (refractory), or recurrence/relapse of the disease. Applicable treatment may vary depending on the type of cancer. Combination therapies of multiple drugs including anticancer agents⁹⁾ are generally used.

Trademarks used or mentioned in this release are protected by law.

Source:

1. Dornan D, et al. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma. Blood 2009; 114:2721-2729
2. Pfeifer M, et al. Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma subtypes. Leukemia 2015; 29:1578-1586
3. Ducry L, Stump B. Antibody-drug conjugates: linking cytotoxic payloads to monoclonal antibodies. Bioconjug Chem. 2010; 21:5-13
4. ADC Review. What are antibody-drug conjugates? Available from: https://www.adcreview.com/the-review/what-are-antibody-drug-conjugates/ [Accessed in August 2022]
5. Tilly H, et al. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. New Eng J Med. 2021.
6. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press; 2008.
7. Maurer JM, 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.
8. Globocan 2020. World Fact Sheet. https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf [Cited from internet. Accessed in August 2022]
9. Center for Cancer Control and Information Services, National Cancer Center. Glossary “salvage therapy” https://ganjoho.jp/public/qa_links/dictionary/dic01/modal/kyuenryoho.html [Cited from internet. Accessed in August 2022, Japanese only]