AbbVie announced two Phase 3 studies evaluating veliparib, an investigational, oral poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor did not meet their primary endpoints. The studies evaluated veliparib in combination with the chemotherapy regimen carboplatin and paclitaxel in patients with squamous non-small cell lung cancer (NSCLC) and triple negative breast cancer (TNBC).
The Phase 3 NSCLC Study was a randomized, double-blind, multicenter, Phase 3 clinical trial and was designed to evaluate the efficacy and safety of veliparib combined with carboplatin and paclitaxel compared to placebo plus carboplatin and paclitaxel in patients with previously untreated metastatic or advanced squamous non-small cell lung cancer. Patients were evaluated based on their smoking status. The intent-to-treat population of 970 patients was stratified by smoking history: those who had smoked within the past 12 months and had more than 100 smoking events in their lifetime; those who had more than 100 smoking events in their lifetime with at least 12 months since the last event; and those who had 100 or fewer smoking events in their lifetime. The primary endpoint was improvement in overall survival in the group of patients who had smoked within the past 12 months and had more than 100 smoking events in their lifetime. Secondary endpoints included improvement in overall survival in the intent-to-treat population, as well as progression-free survival and overall response in the primary endpoint subgroup and in the intent-to-treat population.
The Phase 3 TNBC Study was a randomized, double-blind, multicenter, Phase 3 study of 312 patients was designed to evaluate the efficacy and safety of the addition of veliparib to carboplatin and standard neoadjuvant chemotherapy (paclitaxel) for the treatment of patients with early-stage triple-negative breast cancer. Patients were randomized to three arms, and treated with either a regimen of veliparib combined with carboplatin and paclitaxel, placebo combined with carboplatin and paclitaxel, or placebo combined only with paclitaxel, all followed by doxorubicin plus cyclophosphamide. The primary endpoint was complete pathologic response. Secondary endpoints included breast conservation rate, overall survival and event-free survival.
"Research shows there is a role for PARP inhibitors in cancers associated with DNA repair deficits, such as those with BRCA mutations. In these clinical trials, we wanted to explore whether a PARP inhibitor could augment chemotherapy in patients with squamous non-small cell lung cancer and triple negative breast cancer by disrupting the repair of cancer cells," Gary Gordon, M.D., Ph.D., vice president, oncology clinical development, AbbVie said. "Unfortunately, these data do not support the use of veliparib in combination with chemotherapy in these patients."
"We have a comprehensive and innovative oncology pipeline that will help bring to market meaningful therapies for hematologic malignancies and solid tumors, especially where there continues to be a significant unmet need," Michael Severino, M.D., executive vice president, research and development, and chief scientific officer, AbbVie said.