AbbVie (NYSE: ABBV) released interim results from an ongoing Phase 2 study of its investigational compound veliparib in combination with chemotherapy, which showed a 35 percent improvement (P-value=0.14) in progression-free survival (PFS) and a 30 percent improvement (P-value=0.21) in overall survival (OS) in patients with previously untreated metastatic or advanced non-small cell lung cancer (NSCLC). These results, which evaluated veliparib as a potential treatment for metastatic or advanced NSCLC, were presented for the first time at the 2014 Annual Congress of the European Society for Medical Oncology (ESMO), September 26-30 in Madrid, Spain.
"There is an urgent need to develop novel treatment options for patients with squamous cell carcinoma," said Suresh S. Ramalingam, M.D., director, Division of Medical Oncology, Emory University. "These data demonstrate activity for veliparib in non-small cell lung cancer patients with squamous histology. The combination of veliparib with chemotherapy merits further evaluation in squamous cell lung cancer."
"Veliparib has shown promise in preliminary trials to possibly limit the replicative potential of cancer cells, induce programmed cell death and work in collaboration with chemotherapy," said Gary Gordon, M.D., Ph.D., divisional vice president, oncology clinical development, AbbVie. "Preliminary data from this randomized study suggest that veliparib may help to improve the progression free survival of patients treated with platinum-based chemotherapy, exemplifying AbbVie's commitment to discovering and developing targeted therapies for hard-to-treat cancers, including squamous non-small cell lung cancer."
Phase 2 Combination Trial in Patients with Non-Small Cell Lung Cancer (Abstract 1234)
The Phase 2, randomized, double-blind trial was designed to evaluate the efficacy and safety of veliparib in combination with carboplatin and paclitaxel, two chemotherapeutic medicines. Patients in the squamous histology subgroup randomized to the veliparib arm demonstrated a PFS rate of 6.1 months compared to 4.1 months (HR=0.50; P-value=0.06) and an OS rate of 10.3 months compared to 8.4 months (HR= 0.71; P-value=0.22). Median PFS was improved from 4.2 to 5.8 months, and median OS was improved from 9.1 to 11.7 months. Common adverse events (≥20% of patients) for the veliparib-containing arm included alopecia (39%), anemia (31%), neutropenia (36%), nausea (28%) and peripheral neuropathy (24%). Grade 3 and 4 adverse events (≥10% of patients) included neutropenia (23%) and anemia (10%).
AbbVie initiated a Phase 3 clinical trial evaluating veliparib in patients with squamous NSCLC earlier in 2014 to confirm the results of this Phase 2 study.
Phase 1 Study in Japanese Patients with Non-Small Cell Lung Cancer (Abstract 1213)
Also during ESMO, AbbVie presented data from a Phase 1 study evaluating veliparib in combination with carboplatin and paclitaxel in Japanese patients with NSCLC, which was designed to evaluate the preliminary efficacy of the treatment, as well as the recommended Phase 2 dose. The study demonstrated an overall response rate of 54.5 percent, with six patients achieving a partial response and four demonstrating stable disease ranging from 40 to 143 days. The study also demonstrated co-administration of carboplatin and paclitaxel had no significant effect on veliparib pharmacokinetics.
Common treatment emergent adverse events (≥20% of patients) were leukopenia (100%), neutropenia (100%), anemia (83.3%), thrombocytopenia (75%), increased aspartate aminotransferase (66.7%) and increased alanine aminotransferase (66.7%). Grade 3 or 4 adverse events occurring in more than two patients were neutropenia (12 patients), leukopenia (4 patients), anemia (3 patients) and hyponatremia (2 patients).