AZD8205 Shows Promise in Heavily Pretreated Solid Tumors: ESMO 2024
Key Insights
AZD8205, a novel antibody-drug conjugate, demonstrates a manageable safety profile in heavily pretreated patients with advanced or metastatic solid tumors (search).
The Phase I/II trial of AZD8205 showed promising clinical activity, particularly in gynecologic tumors and breast cancer (search), with partial responses observed.
Common grade 3 or higher adverse effects included neutropenia (search), anemia (search), and decreased white blood cell count, manageable with dose adjustments.
Interim data from a first-in-human Phase I/II trial reveals that the antibody-drug conjugate (ADC) puxitatug samrotecan (AZD8205) exhibits a manageable safety profile and preliminary efficacy in heavily pretreated patients with advanced or metastatic solid tumors (search). The findings, presented at the 2024 European Society for Medical Oncology (ESMO) Congress, suggest AZD8205 could offer a new treatment option for patients with limited alternatives.
The study, led by Funda Meric-Bernstam, M.D., chair of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, included 47 patients with a median age of 57 and a median of five prior lines of treatment. Among the 44 patients treated at a 1.6 mg/kg dose or higher, nine achieved partial responses, including those with ovarian, breast, or endometrial cancer (search).
Safety and Tolerability
While 91.5% of patients experienced treatment-related adverse events of any grade, and 55.3% experienced grade 3 or higher adverse events, only two patients discontinued treatment due to toxicities. The most common grade 3 or higher adverse effects were neutropenia (search) (34%), anemia (search) (17%), and a decrease in white blood cell count (17%), which were managed with dose delays and reductions. This is particularly encouraging given the heavily pretreated nature of the patient population.
Mechanism of Action
AZD8205 is a topoisomerase 1 inhibitor (Top1i) ADC that targets B7-H4 (search), an immunoregulatory protein highly expressed in some solid tumors (search) but with limited expression in normal tissue. High B7-H4 expression is associated with poor prognosis and disease progression. AZD8205 leverages this high expression by binding to B7-H4 and delivering the Top1i payload, disrupting DNA replication and inducing cell death.
Future Directions
"This first-in-human trial with AZD8205 demonstrated promising clinical activity, especially in gynecologic tumors and breast cancer (search), and a safety profile consistent with the mechanism of action," said Meric-Bernstam. "We look forward to additional data from this study as we continue working to advance ADCs as an emerging class of cancer therapy."
Phase II expansion cohorts are currently ongoing, focusing on ovarian, breast, endometrial, and biliary tract cancers. These studies aim to further define the efficacy and safety profile of AZD8205 in specific tumor types.