Originally published June 30.
NEW YORK (GenoomeWeb) – AbbVie has initiated its Phase III trial investigating the safety and efficacy of the investigational PARP inhibitor veliparib in combination with carboplatin and paclitaxel in advanced breast cancer patients.
In the double-blind study, researchers will randomize nearly 300 patients to receive either veliparib, plus the carboplatin/paclitaxel combination, or just the chemotherapy regimen. Metastatic or locally advanced breast cancer patients enrolled in the trial will have to have tumors that are HER2 negative, but positive for BRCA1/2 mutations. AbbVie is working with Myriad Genetics to use its BRACAnalysis test to gauge BRCA mutations in study subjects.
Researchers will assess in the study whether adding veliparib significantly increases patients' progression-free survival compared to treatment with only chemotherapy. Other endpoints in the study are overall survival, clinical benefit rate, objective response rate, and duration of response.
I-SPY2, an adaptive multi-drug, Phase II breast cancer trial, predicted a 90 percent chance of success of a Phase III trial showing that veliparib plus carboplatin and standard chemotherapy was superior to just chemotherapy in triple-negative, neoadjuvant breast cancer patients.
That study and others have suggested that BRCA-deficient breast cancer patients who receive carboplatin, a DNA damaging agent, and a PARP inhibitor, such as veliparib, do better than they would just on carboplatin or a PARP inhibitor alone. The added benefit of veliparib to platinum-containing chemotherapy is what AbbVie is now exploring.
"By adding veliparib to DNA-damaging therapies, such as carboplatin and paclitaxel, we can evaluate its potential to provide incremental benefit to existing treatments," Michael Severino, AbbVie's chief scientific officer, said in a statement.
PARP inhibitors work especially well in patients with BRCA mutations since this class of drugs blocks an enzyme involved in repairing breaks in DNA. People with BRCA mutations already have impaired ability to mend these DNA breaks, and with the help of PARP inhibitors, tumor cells lose their ability to repair DNA damage and die. As such, the idea behind pairing a PARP inhibitor with a DNA damaging agent is to further strengthen this line of attack against malignant cells in BRCA-mutated breast cancer patients.
AbbVie is studying veliparib in various tumor types, including in non-small cell lung cancer patients. This latest breast cancer study is the third trial in the disease setting involving veliparib, and the second trial combining veliparib with chemo in difficult-to-treat patients.