AbbVie’s investigational oral poly(ADP-ribose) polymerase (PARP) inhibitor veliparib failed in two Phase III combination therapy trials in patients with squamous non-small-cell lung cancer (NSCLC) and triple-negative breast cancer (TNBC). The firm confirmed that both studies failed to meet their primary endpoints and said full results would be published or presented at forthcoming medical meetings.
AbbVie vp for oncology clinical development, Gary Gordon, M.D., Ph.D., pointed out that research has indicated the potential utility of PARP inhibitors in repair deficit-related cancers. The reported Phase III studies were designed to evaluate whether veliparib could boost chemotherapy in the two cancer types by disrupting cancer cell repair, he said in a statement. “Unfortunately, these data do not support the use of veliparib in combination with chemotherapy in these patients.”
The failed 970-patient Phase III NSCLC study evaluated veliparib combined with carboplatin and paclitaxel chemotherapy in patients with previously untreated metastatic or advanced squamous NSCLC, who were stratified according to smoking history. The primary endpoint was improvement in overall survival in patients who had smoked within the past 12 months and had more than 100 smoking events in their lifetime.
The Phase III breast cancer study evaluated veliparib in 312 patients with early-stage TNBC. Patients were randomized to one of three treatment regimens—either veliparib plus carboplatin and standard neoadjuvant paclitaxel chemotherapy, or placebo combined with carboplatin and paclitaxel, or placebo combined with paclitaxel. All patients then received doxorubicin plus cyclophosphamide therapy. The primary endpoint was complete pathologic response.
AbbVie’s oncology portfolio includes three marketed drugs, which have been approved in various markets for specific cancer indications. Venclexta™/Venckyxto is a selective small-molecule Bcl-2 inhibitor approved for treating chronic lymphocytic leukemia (CLL) with a 17p chromosomal deletion. Empliciti™ (elotuzumab) is a monoclonal antibody targeting SLAMF7 (surface antigen CD319) and approved as second-line therapy for multiple myeloma. Imbruvica® (ibrutinib) is a Bruton’s tyrosine kinase (BTK) inhibitor approved for treating mantle cell lymphoma, CLL, Waldenström’s macroglobulinemia, and relapsed/refractory marginal zone lymphoma. The three drugs are also in late-stage development for additional indications. AbbVie says it has more than 20 oncology programs in Phase I and preclinical development.
Earlier this month AbbVie reported that the FDA had accepted for review a supplemental New Drug Application for the use of Imbruvica in the treatment of chronic graft-versus-host diseases (cGVHD) in patients who have undergone at least one line of systemic therapy. The drug is being developed jointly by AbbVie’s Pharmacyclics company and Janssen Biotech for oncology and other indications, excluding inflammation and immune-mediated conditions.
The AbbVie veliparib trial failures come less than a month after the FDA approved Tesaro’s oral PARP inhibitor, Zejula™ (niraparib) for maintenance therapy in women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.
At the end of 2016, AbbVie launched separate cancer research collaborations with The Johns Hopkins University School of Medicine and with the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.