The novel antibody-drug conjugate puxitatug samrotecan may have a manageable safety profile consistent with similar antibody-drug conjugates and demonstrated initial efficacy in patients with heavily pretreated advanced or metastatic solid tumors, according to new findings presented by Meric-Bernstam et al at the European Society for Medical Oncology (ESMO) Congress 2024 (Abstract 606O).
Background
Puxitatug samrotecan is a topoisomerase 1 inhibitor antibody-drug conjugate designed to target B7-H4—an immunoregulatory protein that is highly expressed in some solid tumors but has limited expression in normal tissue. High expression of B7-H4 has been associated with a poor prognosis and disease progression. The novel drug aims to turn that high expression into a vulnerability by binding to the B7-H4 protein and delivering the topoisomerase 1 inhibitor payload, which interferes with DNA replication and ultimately leads to cell death.
Study Methods and Results
In the first-in-human phase I/II trial, researchers assigned 47 patients with a median age of 57 years who had undergone a median of five prior lines of therapy to receive puxitatug samrotecan.
Among the 44 patients treated with 1.6 mg/kg doses or higher, 20.5% (n = 9) of them had partial responses, including those with ovarian cancer, breast cancer, and endometrial cancer.
The researchers reported that 91.5% of the patients experienced treatment-related adverse events of any grade and 55.3% of them experienced adverse events above grade 3. However, because this patient population was heavily pretreated, they noted that the fact that only 2 of the patients had to discontinue treatment related to toxicities showed the drug’s potential. The most common adverse effects at grade 3 or higher were neutropenia (34%), anemia (17%), and a decrease in white blood cell count (17%). These adverse events were managed with dose delays and dose reductions.
Conclusions
“This first-in-human trial with [puxitatug samrotecan] demonstrated promising clinical activity, especially in gynecologic tumors and breast cancer, and a safety profile consistent with the mechanism of action,” underscored lead study author Funda Meric-Bernstam, MD, Chair of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center. “We look forward to additional data from this study as we continue working to advance [antibody-drug conjugates] as an emerging class of cancer therapy,” she concluded.
Phase II expansion cohorts are ongoing in ovarian cancer, breast cancer, endometrial cancer, and biliary tract cancer.
Disclosure: The research in this study was funded by AstraZeneca. For full disclosures of the study authors, visit cslide.ctimeetingtech.com.
