| EN

Simcere Announces the Approval of Clinical Trial Application by NMPA to Initiate China Phase Ⅲ Study Sites for the Global Clinical Trial of Trilaciclib in the Treatment of Triple-Negative Breast Cancer (TNBC)

Release time:2021-06-18

On June 10, Simcere Pharmaceutical Group Limited (2096.HK) announced that the clinical trial application for trilaciclib, an innovative drug being developed in cooperation with G1 Therapeutics, INC. (Nasdaq: GTHX), has been approved by the National Medical Products Administration (NMPA), PRC. With this CTA, Simcere plans to initiate clinical trial activity as part of the ongoing global PRESERVE 2 clinical trial run by its partner G1. The trial is a phase Ⅲ trial using trilaciclib in combination with gemcitabine and carboplatin for first-line or second-line treatment of patients with unresectable locally advanced or metastatic triple negative breast cancer (TNBC).

TNBC is a cancer that tests negative for estrogen receptors (ER), progesterone receptors (PR), and excess HER2 protein. About 15~20% of all breast cancers are triple-negative. TNBC is considered to be more aggressive and has a poorer prognosis than other types of breast cancer.

In the TNBC setting, cancer progression is not fueled by hormones such as estrogen and progesterone, or by the HER2 protein. Therefore, TNBC does not respond to hormonal therapy medicines or medicines that target HER2 protein receptors. Chemotherapy remains the standard of care for TNBC even though it is limited by itstoxicity and drives drug resistance in patients. In addition, myelosuppression which is an adverse side effect of chemotherapy damages a patient's immune system, putting patients in the precarious position of being unable to effectively mount immune based anti-cancer responses.

To this day, there has been no significant advancement in developing new treatments for TNBC beyond chemotherapy. Patients still have a significant unmet need for new treatment options. Therefore, there is a major demand to develop new treatments with improved anti-tumor efficacy without causing high toxicity, as in the case with chemotherapy, and is a major focus of exploration in the field of TNBC.

In a Phase II study, administering trilaciclib prior to gemcitabine plus carboplatin (GCb) significantly increased OS compared with GCb alone among patients with TNBC. The global, multicenter, phase II G1T28-04 trial randomly assigned 102 previously treated or treatment-naive patients to one of three treatment arms:

  • Group 1:receive GCb

  • Group 2:trilaciclib prior to GCb on days 1 and 8

  • Group 3:trilaciclib alone on days 1 and 8 and prior to GCb on days 2 and 9 

The primary endpoint of the study was the duration of severe neutropenia in cycle 1 and the occurrence of severe neutropenia at any time during treatment. Progression-free survival (PFS) and overall survival (OS) were key prespecified secondary endpoints.

The results demonstrated that in the first cycle, the three groups had no significant differences in the average duration and incidence of severe neutropenia. Although this primary endpoint was negative, the trilaciclib combination group showed statistically significant results on OS:

Median OS was 12.6 months in Group 1, not reached for Group 2, and 17.8 months in Group 3. The median OS for Groups 2 and 3 combined was 19.8 months (HR=0.37, p<0.0001). In addition to the significant impact on overall survival, trilaciclib also observed numerical improvements in progression-free survival (PFS) and objective response rate (ORR). A further subgroup analysis showed that regardless of the patient's CDK4/6 dependence status and PD-L1 expression, the use of trilaciclib before chemotherapy can benefit, and the PD-L1 positive patient population has a statistically significant improvement.

In recent years, the incidence of breast cancer in China has continued to increase. Simcere will rapidly open clinical sites in China for Chinese patients with TNBC as part of the global clinical trial of trilaciclib, working to provide better treatment options for the popluation.

About Trilaciclib

Trilaciclib (COSELATM) is the first and only myeloprotection therapy to help decrease the incidence of chemotherapy-induced myelosuppression, which received the Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) in 2019 based on positive data in small cell lung cancer patients from three randomized Phase II clinical trials. On February 12, 2021, US FDA approved COSELA to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer (ES-SCLC). On March 25, 2021 trilaciclib has been added to two updated National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines in Oncology: the Treatment Guidelines for Small Cell Lung Cancer and the Supportive Care Guidelines for Hematopoietic Growth Factors. In August 2020, Simcere has reached a cooperation agreement with G1 Therapeutics, INC. to be responsible for the development and commercialization of Trilaciclib in all indications in Greater China (Mainland China, Hong Kong, Macau and Taiwan).

Forward Looking Statements

Information set forth in this press release contains forward-looking statements, which involve a number of known and unknown risks, uncertainties and assumptions. The forward-looking statements contained herein reflect the current judgment and views of Simcere Pharmaceutical Group Limited as of the date of this press release. Such forward-looking statements are neither promises nor guarantees but are subject to a variety of risks and uncertainties, many of which are beyond our control, or may not materialize, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any such statements, whether as a result of new information, future events or otherwise, to reflect any change in our expectations or any change in events, conditions or circumstances on which any such statement is based.