AstraZeneca, Daiichi Will Seek Approval Following ADC Trial Success In Advanced Breast Cancer
Executive Summary
AstraZeneca and Daiichi said their pivotal Phase II DESTINY-Breast01 trial assessing the HER2-targeting antibody drug conjugate trastuzumab deruxtecan met its primary endpoint, supporting global regulatory submission plans starting in this year’s second half.
Positive Phase II data using trastuzumab deruxtecan to treat advanced HER2-positive breast cancer will now be used by AstraZeneca PLC and Daiichi Sankyo Co. Ltd. to back regulatory submissions around the world, and give further credence to their alliance to jointly commercialize the novel antibody-drug conjugate.
The duo said on 8 May that their pivotal DESTINY-Breast01 trial had met its primary endpoint by demonstrating "a clinically meaningful" response rate in patients with refractory HER2-positive metastatic breast cancer, confirming impressive clinical activity in a recently published Phase I trial.
"If these results replicate or improve upon the strong preliminary data from Phase I, the drug is likely to become a standard choice in HER2-refractory breast cancer patients." – Zachary McLellan
The safety and tolerability profile of trastuzumab deruxtecan shown in DESTINY was also consistent with previous experience. The companies said they would present the DESTINY trial data at an upcoming medical meeting, but gave no details.
Planned Regulatory Filings
The results will back planned regulatory submissions, including a biologics license application with the US Food and Drug Administration anticipated in the second half of 2019.
Under their pact, Daiichi Sankyo will file and be the BLA holder of trastuzumab deruxtecan in US and other markets where it is the lead development partner, such as Japan.
AstraZeneca will file in markets where it is the lead development party, such as in China.
José Baselga, who heads R&D Oncology at AstraZeneca. said, "We believe this antibody drug conjugate has the potential to redefine the treatment of patients with HER2-expressing cancers, and we are eager to bring it as quickly as possible to patients with refractory HER2-positive breast cancer."
Reflect Unmet Need
About one in five patients with breast cancer have tumors that overexpress the HER2/neu gene, a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells and which is associated with aggressive disease. There is no current standard of care for HER2-positive tumors after treatment with Roche’s Herceptin (trastuzumab), Perjeta (pertuzumab) and Kadcyla (trastuzumab emtansine), so this remains a population with high unmet medical need.
"Without the full dataset its difficult to determine trastuzumab deruxtecan’s full potential in this indication, but if these results replicate or improve upon the strong preliminary data from Phase I, the drug is likely to become a standard choice in HER2-refractory breast cancer patients," said Datamonitor Healthcare analyst Zachary McLellan.
In that Phase I trial, trastuzumab deruxtecan demonstrated a robust 20.7-month duration of response and 22.1-month median PFS in HER2+ breast cancer patients.
With regulatory submission based on these results planned for later this year, AstraZeneca is now set to gain a foothold in the lucrative HER2+ breast cancer market currently dominated by Roche and its stable of HER2-targeted regimens (Herceptin, Perjeta, and Kadcyla).
"Competition from these established brands should be minimal, however, due to trastuzumab deruxtecan’s positioning," McLellan told Scrip.
AstraZeneca has aimed trastuzumab deruxtecan at heavily pretreated patients that have already received Kadcyla, Roche’s own antibody drug conjugate, which is typically used post-Herceptin. As such, trastuzumab deruxtecan’s targeted patients have likely already failed several HER2-directed therapies in addition to Kadcyla and have few, if any, treatment options available, the analyst noted.
And High Ambitions
AstraZeneca and Daiichi said they have high ambitions for trastuzumab deruxtecan, also known as DS-8201.
A broad and comprehensive development program with trastuzumab deruxtecan is underway in North America, Europe and Asia, including five pivotal trials in HER2-expressing breast and gastric cancers, including in breast cancer patients with HER2-low expression.
Trastuzumab deruxtecan is also in Phase II development for HER2-expressing advanced colorectal cancer and metastatic non-squamous HER2-overexpressing or HER2-mutated non-small cell lung cancer (NSCLC), and Phase I development in combination with nivolumab for HER2-expressing metastatic breast and bladder cancers.
Analysts said the DESTINY trial results should increase confidence for trials in earlier lines of metastatic breast cancer, readouts from which are expected in the first half of 2022.
"The major metastatic breast cancer opportunity is the HER2 low patients, data from which is due in the first-half of 2022. Advanced gastric cancer results are also expected in the second half of 2019, and could raise expectations for other HER2+ solid tumors," analysts at BMO Capital Markets said in a reaction note to investors on 8 May.