AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan) has been recommended for approval in the European Union (EU) as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+) solid tumours who have received prior treatment and who have no satisfactory treatment options.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on results from a subgroup of patients with HER2-positive (IHC 3+) tumours across three Phase II trials, DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02, in which Enhertu demonstrated clinically meaningful responses across a broad range of tumours.
Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "HER2-directed therapies have already transformed care for certain HER2-expressing cancers, including breast and gastric cancers. However, many other cancers overexpress HER2, and targeted treatment options remain unavailable for most of these tumour types. This positive CHMP opinion underscores the importance of precision oncology and marks an important step toward bringing a new targeted option to more patients in the EU living with HER2-positive solid tumours."
John Tsai, Global Head, R&D, Daiichi Sankyo, said: "This positive CHMP opinion acknowledges the clinical value of Enhertu as the potential first HER2-directed medicine and antibody drug conjugate available for patients with HER2-positive metastatic solid tumours in the EU. Enhertu offers meaningful responses for patients with advanced cancers that overexpress HER2 who have limited treatment options. We look forward to continuing to work with the EMA to bring Enhertu to these patients."
In the DESTINY-PanTumor02 Phase II trial, Enhertu demonstrated a confirmed objective response rate (ORR) of 51.4% and median duration of response (DOR) of 14.2 months in previously treated patients with centrally or locally assessed IHC 3+ solid tumours (n=111) including either biliary tract, bladder, cervical, endometrial, ovarian, pancreatic or other tumours. In DESTINY-Lung01, Enhertu demonstrated a confirmed ORR of 52.9% and median DOR of 6.9 months in patients with centrally confirmed IHC 3+ non-small cell lung cancer (NSCLC) (n=17). In DESTINY-CRC02, Enhertu demonstrated a confirmed ORR of 46.9% and median DOR of 5.5 months in patients with centrally confirmed IHC 3+ colorectal cancer (n=64).
The safety profile of Enhertu was consistent with previous clinical trials with no new safety concerns identified.
Enhertu has received a tumour agnostic indication in the US and other countries based on the DESTINY-PanTumor02 trial.
Additional regulatory submissions for Enhertu are under review in the EU, including in combination with pertuzumab for the 1st-line treatment of patients with unresectable or metastatic HER2-positive (IHC 3+ and ISH+) breast cancer based on data from the DESTINY-Breast09 Phase III trial and for patients with HER2-positive (IHC 3+ and ISH+) breast cancer who have residual invasive disease after neoadjuvant HER2-targeted treatment based on data from the DESTINY-Breast05 Phase III trial.
Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
Notes
HER2 expression in solid tumours
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of various tissue cells throughout the body and is involved in normal cell growth.1 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in some cancers.2
HER2-directed therapies have been used to treat HER2 overexpression in breast, gastric and salivary gland cancers in the EU.1,3-5 Although HER2 is overexpressed in additional solid tumour types including biliary tract, lung, bladder, cervical, colorectal, endometrial, ovarian and pancreatic cancers, HER2 testing is not routinely performed for these additional tumour types and there are currently no HER2 directed treatments approved in the EU to treat a broad range of solid tumours.6,7
DESTINY-PanTumor02
DESTINY-PanTumor02 is a global, multicentre, multi-cohort, open-label, Phase II trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) for the treatment of previously treated HER2-expressing tumours, including biliary tract, bladder, cervical, endometrial, ovarian, pancreatic cancer or other tumours.
The primary endpoint of DESTINY-PanTumor02 is confirmed ORR as assessed by investigator. Secondary endpoints include DOR, disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, tolerability and pharmacokinetics. Results from DESTINY-PanTumor02 were published in the Journal of Clinical Oncology.8
