Daiichi Sankyo and AstraZeneca’s TROP2 ADC Datopotamab Deruxtecan Approved in China for HR+/HER2- Metastatic Breast Cancer

On August 22, the NMPA website showed that Daiichi Sankyo submittedDatozumab, a TROP2-targeted ADC co-developed and co-marketed with AstraZeneca（Datopotamab deruxtecan，Dato-DXd）ApprovedListed,Used for treatmentPatients who have previously received endocrine therapy and at least one line of chemotherapy at the advanced disease stage, with unresectable or metastatic hormone receptor（HR）Positive, Human Epidermal Growth Factor Receptor 2（HER2）Negative(IHC 0, IHC 1+ or IHC 2+/ISH-)Adult Patients with Breast Cancer。

Screenshot from:NMPA Official Website

The approval and market launch of Debozumab this time is based on the pivotal Phase III clinical trial. TROPION-Breast 01 Research Data.

This is a global, randomized, multicenter, open-label Phase III study designed to evaluate Dato-DXd versus investigator's choice of chemotherapy regimen.(Eribulin, Capecitabine, Vinorelbine or Gemcitabine)In patients assessed by the investigator as having disease progression after prior endocrine therapy or being unsuitable for endocrine therapy, and having received at least one systemic treatment, with inoperable or metastatic HR-positive, HER2-low, or HER2-negative.(IHC0, IHC1+ or IHC2+/ISH-)Efficacy and Safety in Patients with Breast Cancer.

TROPION-Breast01The two primary endpoints are PFS(Evaluated by BICR)And OSKey secondary endpoints included ORR, duration of response, investigator-assessed PFS, disease control rate, and time to first subsequent treatment.

TROPION-Breast01This study is the first Phase III clinical trial of Dato-DXd in breast cancer to report results, aiming to evaluate the efficacy and safety of Dato-DXd compared with investigator-selected chemotherapy regimens in patients with unresectable or metastatic HR-positive, HER2-low or negative (IHC 0, IHC 1+, or IHC 2+/ISH-) breast cancer who have previously received endocrine therapy and at least one systemic therapy. The primary endpoints are PFS and OS assessed by BICR.

The results of the study, presented at the 2023 ESMO Congress, showed that in terms of the primary endpoint PFS, assessed by BICR, compared with investigator-selected chemotherapy（ICC）In comparison, Dato-DXd is used for HR-positive, HER2-negative patients who have undergone endocrine therapy.(IHC0, IHC1+ or IHC2+/IHC-)Patients with metastatic breast cancer,Can significantly reduce the risk of disease progression or death by 37%（HR = 0.63；95% CI: 0.52-0.76；p<0.0001）。

Dato-DXd Treatment GroupMedian PFS was 6.9 months, while the chemotherapy group was 4.9 months. Consistent PFS benefits were observed across different subgroups. Additionally,The ORR in the Dato-DXd group was 36.4%., while the chemotherapy group was 22.9%.

Screenshot source: Official WeChat account of the company

In the interim analysis of the other primary endpoint OS in the study, as of the data cutoff date, Dato-DXd also showedSuperior to Chemotherapy OS Improvement Trend（HR = 0.84；95% CI: 0.62-1.14）. The study is currently ongoing and will further evaluate OS.

Screenshot source: Official WeChat account of the company

In terms of safetyDato-DXd demonstrated a favorable overall safety profile, with no new safety concerns identified. Grade 3 or higher treatment-related adverse events occurred in both the Dato-DXd treatment group and the chemotherapy group.（TRAE）The incidence rates were 21% and 45%, respectively, with the Dato-DXd group being less than half of the chemotherapy group.

September 2024, Daiichi SankyoAstraZeneca Co-Announces Phase III TROPION-Breast01 Study of Dato-DXdDid Not Reach OS Primary Endpoint。

AstraZeneca stated that the PFS benefit for patients failed to translate into a statistically significant improvement in OS, possibly due to the subsequent treatments received by patients during the clinical trial period. ADC drugs, including Enhertu, were approved and marketed during this time, and patients participating in the trial received these treatments after progression, impacting the OS results.

Insight database shows,InBreast Cancer Field, Daiichi Sankyo/AstraZeneca have jointly conducted 5 Phase III clinical trials, exceptIn addition to HR+/HER2- breast cancer, it also includes first-line therapy for metastatic triple-negative breast cancer as well as adjuvant therapies, etc.

Beyond breast cancer, progress is also being made inLung CancerProgress in the field. In June 25, the drug received FDA approval.Approved for Marketing, used forTreatment of locally advanced or metastatic EGFR-mutated non-small cell lung cancer previously treated with EGFR-targeted therapy and platinum-based chemotherapy (NSCLC) Adult patients.

In addition, the two companies are also exploringDato-DXd is used forUrothelial carcinoma, colorectal cancer, endometrial cancer, gastric cancerThe potential for other cancer types.

Screenshot source: Insight Database