Trastuzumab deruxtecan

Unassigned

New Medicines

Enhertu · Metastatic breast cancer, unresectable or metastatic, HER2-positive, at least two previous anti-HER2 regimens

Information

Enhertu
New molecular entity
Daiichi Sankyo
Daiichi Sankyo

Development and Regulatory status

None
None
Approved (Licensed)
Mar 20 · EU filing based on DESTINY-Breast01 planned for H2 20 [12].
Feb 20 · Analysts predict this will be one of the top 10 most-anticipated new US drug launches of 2020 based on estimated global sales in 2024 [11].
Dec 19 · Filings based on data from DESTINY-Breast 02 expected in 2021 [10].
Dec 19 · Approved in US via accelerated approval process, based on tumour response rate; continued licensing may be conditional on confirmation of clinical benefit [9].
Oct 19 · Filed in US with priority review [7].
Sep 19 · Filings based on DESTINY-Breast 01 planned for H2 2019 [6].
Jun 19 · Filings planned for 2020+ [5].
Aug 17 · US FDA grants Breakthrough Therapy Designation to trastuzumab deruxtecan for treatment of patients with HER2-positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after ado-trastuzumab emtansine (T-DM1) [3].
Dec 16 · US FDA grants Fast Track designation to trastuzumab deruxtecan for treatment of HER2-positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2-targeted therapies including ado-trastuzumab emtansine [3].

Category

Antibody-drug conjugate composed of an anti-HER2 antibody, trastuzumab, and a DNA topoisomerase I inhibitor, a DX 8951 derivative. The HER2 antibody is attached to the topoisomerase I inhibitor by a tetrapeptide linker.
In 2014, there were approximately 46,500 new diagnoses of breast cancer in England. It is estimated that approximately 15-25% of women with breast cancer will have HER2-positive tumours [1].
Metastatic breast cancer, unresectable or metastatic, HER2-positive, at least two previous anti-HER2 regimens
Intravenous infusion

Trial or other data

Dec 19 · Results from the PII, single arm DESTINY-Breast01 trial found that trastuzumab deruxtecan led to an objective response rate of 60.9%. A cure rate of 6% was seen, and disease control rate of 97% (including some patients who experienced some tumour shrinkage, but not sufficient to be considered responders). Patients had received an average of six prior treatments. Side effects were experienced by 99% of patients, which included nausea, vomiting and low white blood cell counts. 15% of patients stopped treatment due to adverse events. Interstitial lung disease was experienced by 25 patients, four of whom died from the disease [8].
May 19 · AstraZeneca and Daiichi Sankyo announce PII DESTINY-Breast01 trial meets primary endpoint of objective response rate. Submission of a NDA to US FDA is planned for the second half of this year [4].
Aug 18 · PIII DESTINY-Breast03 trial to compare the anti-tumour activity as well as the safety and efficacy of trastuzumab deruxtecan versus T-DM1 (trastuzumab emtansine) in HER2-positive, unresectable and/or metastatic breast cancer subjects previously treated with trastuzumab and taxane (DS8201A-U302; NCT03529110). Progression-free survival is the primary endpoint of the trial. 500 patients will be recruited in the US and Japan. Collection of primary outcome data should complete Feb 22 [2].

Evidence based evaluations

Enhertu · Metastatic HER2-low breast cancer

Information

Enhertu
Licence extension / variation
Daiichi Sankyo
Daiichi Sankyo

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials

Category

Phase III Clinical Trials
In 2014, there were approximately 46,500 new diagnoses of breast cancer in England. It is estimated that approximately 15-25% of women with breast cancer will have HER2-positive tumours [1].
Metastatic HER2-low breast cancer
Intravenous infusion

Enhertu · Unresectable or metastatic, HER2-positive breast cancer - second-line

Information

Enhertu
Licence extension / variation
Daiichi Sankyo
Daiichi Sankyo

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Antibody-drug conjugate composed of an anti-HER2 antibody, trastuzumab, and a DNA topoisomerase I inhibitor, a DX 8951 derivative. The HER2 antibody is attached to the topoisomerase I inhibitor by a tetrapeptide linker.
In 2014, there were approximately 46,500 new diagnoses of breast cancer in England. It is estimated that approximately 15-25% of women with breast cancer will have HER2-positive tumours [1].
Unresectable or metastatic, HER2-positive breast cancer - second-line
Intravenous infusion