Oncology / Clinical Trials | Phase 2a Study Data

New trial data show alnodesertib may slow ovarian cancer progression

Trial tested whether targeting DNA repair could improve chemotherapy response.

A low dose of alnodesertib (ART 0380) added to standard chemotherapy significantly reduced the likelihood of disease progression among people with platinum-resistant high-grade serous ovarian carcinoma (HGSOC) in an early clinical trial.

Findings from the Phase 2a study (NCT04657068) were announced by Artios Pharma, which is developing alnodesertib and sponsored the trial.

“The encouraging clinical signals we observed in patients when low dose alnodesertib was added to gemcitabine suggest that this approach warrants further evaluation.” Antonio Gonzalez-Martin, MD, PhD Trial’s Principal Investigator at Clínica Universidad de Navarra in Spain (Artios press release)

Why platinum-resistant ovarian cancer is difficult to treat

GSOC is a form of gynecological cancer marked by the uncontrolled growth of cells in or around the ovaries. First-line treatment usually involves platinum-based chemotherapies, but many patients eventually stop responding to these drugs.

“With approximately 70% of patients with ovarian cancer eventually relapsing following platinum-based chemotherapy, there is a high unmet need for promising new therapies like alnodesertib to improve clinical outcomes in platinum-resistant HGSOC and other tumors with high replication stress.” Antonio Gonzalez-Martin, MD, PhD

Mechanism of Action: Targeting DNA Repair

For cells to divide, they must copy their DNA. When this process happens rapidly, as in fast-growing tumors like HGSOC, mistakes can occur, leading to DNA damage. This process, known as replication stress, can be deadly for cancer cells if they cannot repair the resulting DNA damage. Many cancer cells rely on a DNA repair protein called ATR (ataxia telangiectasia and Rad3-related) to help fix DNA damage caused by replication stress.

Alnodesertib, formerly known as ART 0380, is an oral therapy designed to block ATR activity, leaving cancer cells more vulnerable to DNA damage. The experimental medication is designed to work alongside existing gynecologic cancer treatments such as gemcitabine, a chemotherapy that damages cancer-cell DNA.