AZD8205, A PROMISING ANTIBODY DRUG CONJUGATE (ADC) FOR THE TREATMENT OF METASTASIS ENDOMETRIAL CARCINOMA AND BREAST CANCER

Within the group of ADCs, there is a new agent, AZD8205, that targets the B7-H4 protein. The expression of B7-H4 is remarkably high (30-40%) in tumour cells across multiple malignancies, including endometrial, breast, ovarian cancers. This high expression of the protein in tumour cells, and its low expression in normal cells, makes it an attractive target for ADCs 1.

AZD8205 was developed by AstraZeneca and is administered intravenously. The drug consists of a human anti-B7-H4 antibody, linked via a degradable linker to a topoisomerase I inhibitor (TOP1i). Clinical results of TOP1i ADCs are promising, including in breast cancer. Preclinical studies on AZD8205 have shown encouraging results, demonstrating antitumor activity 2.

NCT05123482 study

The NCT05123482 study is the first trial where AZD8205 is being administered to patients with metastatic solid tumors. It is an open-label Phase I/IIa study, with the primary objective of determining the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of AZD8205.

At the Center for Early Clinical Research (part of the NKI-AVL), the study is led by Dr. Marloes van Donge. Patients with endometrial and ER-positive breast cancer are currently (June 2024) eligible to participate.

The main inclusion criteria are:

  • Age of 18 years or older.
  • Metastatic disease: patients with endometrial cancer must have received at least 1 and a maximum of 2 lines of chemotherapy; patients with ER positive, HER2 negative breast cancer, at least 1 and a maximum of 3 lines of chemotherapy.
  • ECOG Performance Status: 0-1.
  • Measurable disease according to RECIST v1.1.
  • Adequate organ function.
  • A life expectancy of 12 weeks or longer.

For the complete list, see clinicaltrials.gov.

Patients who qualify for this study can be referred to our phase 1 outpatient clinic (AvL study code M23ABD). Read here on how to refer a patient to Antoni van Leeuwenhoek (AvL).

For references/referrals and questions regarding the study and procedures, please contact the Early Clinical Research Center of AvL/NKI via Fase1@nki.nl.

References:

1. Podojil JR, Miller SD. Potential targeting of B7-H4 for the treatment of cancer. Immunol Rev. 2017;276(1):40-51. doi:10.1111/imr.12530

2. Meric-Bernstam F, Oh DY, Naito Y, et al. First-in-human study of the B7-H4 antibody-drug conjugate (ADC) AZD8205 in patients with advanced/metastatic solid tumors. J Clin Oncol. 2022;40(suppl 16):TPS3153. doi:10.1200/JCO.2022.40.16_suppl.TPS3153.