Study to Investigate If Novel Drug Overcomes PARP Inhibitor Resistance in Breast Cancer

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A phase 2 trial will analyze the novel drug ART4215 with Talzenna, a PARP inhibitor, for patients with BRCA-deficient breast cancer.

A phase 2 expansion study is now underway, examining the novel drug ART4215 with the PARP inhibitor Talzenna (talazoparib) for patients with BRCA-deficient breast cancer.

ART4215 inhibits polymerase theta (Polθ), an enzyme that, when overproduced, can lead to poor outcomes for patients with breast cancer. The drug has shown promise in prior pre-clinical studies, according to Artois, the pharmaceutical company manufacturing ART4215.

“Polθ is highly expressed in cancer cells, but has limited expression in healthy cells, making it an attractive cancer target,” Dr. Niall Martin, CEO of Artois, said in a press release. “Initial phase 1 data supports a favorable tolerability profile and the potential for broad treatment use, particularly in combination with agents like PARP inhibitors where combinations with other DNA damage response inhibitors have been limited by toxicity.

The ongoing global phase 1/2 study of the drug will evaluate the safety, tolerability, pharmacokinetics (how the drug moves throughout the body) and clinical activity of ART4215, both as a single agent and when given in combination with Talzenna, which was approved in 2018 for BRCA-mutant, HER2-negative locally advanced or metastatic breast cancer.

Early data from the phase 1 portion of the study showed that ART42115 was well-tolerated, so researchers decided to expand their research to phase 2, which will include up to 206 patients with BRCA-deficient breast cancer in the United States and Europe.

“We are highly encouraged that ART4215 may offer a new treatment option that can synergize to overcome both de novo and acquired PARP resistance,” Martin said.

The study’s principal investigator, Dr. Erika P. Hamilton, director of the Breast Cancer and Gynecologic Cancer Research Program at the Sarah Cannon Research Institute at Tennessee Oncology, said that while effective, there are unmet needs associated with PARP inhibitors that must be addressed.

“Patients with advanced solid tumors have achieved improved outcomes with the development of PARP inhibitors,” she said in the release. “However, there is still a need to address resistance mechanisms diminishing initial tumor responses and leading to disease progression. ART4215 has the potential to help overcome these limitations, and we are excited that the initiation of this phase 2 trial represents an important step in the clinical evaluation of Polθ as a novel target.”

Data from the phase 1 portion of the trial will be reported during the first half of 2023, according to Martin.

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