News

2022-08-29

Dalpiciclib in Combination with Letrozole or Anastrozole Significantly Improved Progression-free Survival in Systemic Treatment-naive, HR-positive, HER2-negative Locally Advanced or Metastatic Breast Cancer

Shanghai, China – August 29, 2022 – Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Hengrui Pharma) announced that the phase III placebo-controlled, double-blind SHR6390-III-302 trial evaluating dalpiciclib, a CDK4/6 inhibitor, in combination with aromatase inhibitors (letrozole or anastrozole) in hormone receptor (HR)-positive, human epidermal growth factor receptor (HER2)-negative advanced breast cancer met the primary endpoint of progression-free survival (PFS). The interim analysis showed that dalpiciclib in combination with aromatase inhibitors as a first-line treatment significantly improved the PFS in HR+, HER2- locally advanced or metastatic breast cancer patients versus placebo in combination with aromatase inhibitors.



About SHR6390-III-302 Trial

The SHR6390-III-302 study is a multi-center, randomized, controlled, double-blind phase III clinical study evaluating the efficacy and safety of dalpiciclib in combination with letrozole or anastrozole versus placebo in combination with letrozole or anastrozole as a first-line treatment for HR-positive, HER2-negative locally advanced or metastatic breast cancer.


The study was initiated in July 2019 and was randomized 2:1 with a total of 456 subjects. The primary endpoint was investigator-assessed progression-free survival (PFS), and secondary endpoints included Independent Review Committee (IRC)-assessed PFS, overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), and safety. The study recently completed the interim analysis of the primary endpoint, PFS, and IDMC determined that the results of the interim analysis of the primary endpoint met the protocol's preset superiority criteria.



About Breast Cancer

According to the GLOBOCAN 2020 report, breast cancer has become the number one malignant tumor in the world and one of the most common malignant tumors in women. Data show that in 2020, there were about 2.261 million cases of newly diagnosed female breast cancer worldwide, accounting for 24.5% of all new cases of malignant tumors in women1. In 2020, there were about 416,000 new cases of breast cancer in China and about 117,000 deaths2. At present, the incidence of breast cancer has increased rapidly, and it has ranked first in the incidence of female tumors. Nearly 50% of patients will experience recurrence and metastasis after treatment. Hormone receptor (HR)-positive breast cancer accounts for about 70% of all breast cancers3.


Endocrine therapy is the standard of care for patients with HR-positive breast cancer, but primary and secondary resistance to endocrine therapy often leads to treatment failure due to disordered and excessive cell proliferation. Due to the control of cyclin and its cyclin-dependent kinase (CDK), the mitotic cycle of normal adult cells is mostly slowed down and arrested. Cyclin D1 and its CDK4 and CDK6 mainly control the mitotic cycle of cells from DNA synthesis prophase to DNA synthesis. Under the stimulation of estrogen and estrogen receptors, cyclin D1 binds to its CDK4 and CDK6 to phosphorylate the tumor suppressor protein Rb, causing its loss of tumor suppressor effect; the mitotic cycle of the cells is thus out of control, leading to disordered and excessive cell proliferation4. For HR+ breast cancer patients who are resistant to endocrine therapy, CDK4 and CDK6 inhibitors effectively block the vicious cycle caused by uncontrolled cell cycle. Therefore, CDK4 and CDK6 become important molecular targets for HR+ breast cancer patients. CDK4/6 inhibitors, as new targeted therapy drugs, combined with endocrine therapy can significantly improve the progression-free survival of patients with HR-positive, HER2-negative advanced breast cancer5.


About Dalpiciclib

Dalpiciclib (SHR6390) is a novel, orally-administered, selective CDK4/6 inhibitor developed by Hengrui. It was approved by the National Medical Products Administration (NMPA) in December 2021, in combination with fulvestrant for patients with HR-positive, HER2-negative recurrent or metastatic breast cancer who have progressed after previous endocrine therapy.


About Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Hengrui Pharma is a leading global pharmaceutical company headquartered in China with a focus on research, development, manufacturing, and commercialization of innovative and high-quality healthcare products. Innovation is the core development strategy. Hengrui Pharma ranked the 24th among the top 1,000 global pharma companies in 20216. Hengrui Pharma has been on the Pharma Exec’s annual listing of the top global pharmaceutical companies for the fourth consecutive year, rising from the 47th in 2019 to the 32nd in 20227.



Reference

1.  Sung H, Ferlay J, Siegel RL, et al: Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71:209-249, 2021

2.  Cao W, Chen HD, Yu YW, Li N, Chen WQ. Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020. Chinese Medical Journal. Apr 5;134(07):783-91, 2021

3.  Anderson W F, Chatterjee N, Ershler W B, et al. Estrogen Receptor Breast Cancer Phenotypes in the Surveillance, Epidemiology, and End Results Database[J]. Breast Cancer Research and Treatment, 2002, 76(1):27-36.

4.  Shapiro GI: Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol 24:1770-83, 2006.

5.  Marra A, Curigliano G. Are all cyclin-dependent kinases 4/6 inhibitors created equal?[J]. NPJ Breast Cancer, 2019, 5(1).

6.  https://torreya.com/publications/pharma-1000-report-torreya-2021-11-08.pdf.

7.   https://www.pharmexec.com/view/2022-pharm-exec-top-50-companies



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