AZ, Daiichi Sankyo reveal new TNBC data for next-gen antibody drug conjugate

AstraZeneca (AZ) and Daiichi Sankyo have revealed new data for their second next-generation antibody drug conjugate (ADC), datopotamab deruxtecan in a group of heavily pre-treated triple negative breast cancer (TNBC) patients.

The preliminary data from the TNBC cohort of the phase 1 TROPION-PanTumor01 study demonstrated an objective response rate (ORR) of 43% in 21 evaluable patients treated with the ADC.

Investigators also observed five confirmed complete responses (CR) or partial responses (PR) as well as a disease control rate of 95%, with four additional CR/PRs awaiting confirmation at the data cut-off on 8 January 2021.

Patients involved in the TROPION-PanTumour01 study were treated with a median of four prior lines of therapy, with a majority having received more than two previous lines of treatment, including a taxane, chemotherapy, immunotherapy, Trodelvy (sacituzumab govitecan) and a PARP inhibitor.

"Triple negative breast cancer is known to be particularly aggressive and fast growing, and after treatment the risk of recurrence is faster and higher than in any other breast cancer subgroup," said Cristian Massacesi, senior vice president, head of late stage development oncology R&D, AZ.

"The preliminary results for datopotamab deruxtecan in this cohort of pretreated patients are encouraging for this high-potential targeted ADC,” he added.

Datopotamab deruxtecan is the second ADC in development as part of AZ and Daiichi’s partnership, the first being Enhertu (trastuzumab deruxtecan).

In December 2019, Enhertu won approval from the US Food and Drug Administration for metastatic HER2-positive breast cancer patients who have previously been treated with two or more anti-HER2-based regimens.

The drug was then approved in the EU in the same indication earlier this year, based on positive results from the single-arm DESTINY-Breast01 trial.

Following the success of Enhertu, AZ invested up to $6bn to develop datopotamab deruxtecan – then known as DS-1062.

Under the terms of the deal, AZ paid Daiichi $1bn upfront in staged payments, with additional conditional amounts of up to $1bn when the drug achieves regulatory approval and up to $4bn for sales-related milestones.

Both companies will jointly develop and commercialise datopotamab deruxtecan worldwide, apart from in Japan where Daiichi will retain exclusive rights.

In addition to TNBC, datopotamab deruxtecan is in development for the treatment of a number of tumour types which express the cell-surface glycoprotein TROP2.

TROP2 is over-expressed in the majority of non-small cell lung cancers (NSCLC) and breast cancers, having been found to be expressed in up to 80% of triple-negative breast cancer patients and can also be identified in the majority of NSCLC patients.