AstraZeneca PLC and Daiichi Sankyo announced Positive high-level results from the DESTINY-Breast06 Phase III trial showed that ENHERTU (fam-trastuzumab deruxtecan-nxki) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to standard-of-care chemotherapy in the primary trial population of patients with HR-positive, HER2-low (IHC 1+ or 2+/ISH-) metastatic breast cancer following one or more lines of endocrine therapy. A statistically significant and clinically meaningful improvement in PFS was also observed in the overall trial population (patients with HER2-low and HER2-ultralow [defined as IHC 0 with membrane staining; IHC >0<1+] metastatic breast cancer). A prespecified subgroup analysis showed the clinically meaningful improvement was consistent between patients with HER2-low and HER2-ultralowexpression.

Overall survival (OS) data were not mature at the time of the analysis; however, ENHERTU showed an early trend towards an OS improvement versus standard-of-care chemotherapy in patients with HER2-low metastatic breast cancer and in the overall trial population. The trial will continue as planned to further assess OS and other secondary endpoints. ENHERTU is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo.

It is estimated that approximately 60-65% of HR-positive, HER2-negative breast cancers are HER2-low and potentially an additional 25% may be HER2-ultralow. Endocrine therapies are widely used in the early lines of treatment for HR-positive metastatic breast cancer; however after two lines of treatment, further efficacy from endocrine therapy is often limited. The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes.

Indications ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with: Unresectable or metastatic HER2-positive (IHC 3+ or ISH positive) breast cancer who have received a prior anti-HER2-based regimen either: In the metastatic setting, or In the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy Unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy Unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH positive) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen Unresectable or metastatic HER2-positive (IHC3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options This indication is approved under accelerated approval based on objective response rate and duration of response.

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.