A phase III trial of the investigational monoclonal antibody necitumumab has met its primary endpoint of improving overall survival in patients who received the drug in combination with gemcitabine and cisplatin as a first-line therapy for metastatic squamous non-small cell lung cancer (NSCLC) when compared with chemotherapy alone, according to an announcement from Lilly, the drug’s manufacturer.
Lilly did not provide specific data regarding the results of the trial, but the company announced that it plans to present that data at a scientific meeting next year, and to request a review of the drug by regulatory authorities before the end of 2014.
“We are pleased with these data which represent a potential advance in treatment for patients with squamous non-small cell lung cancer, which is a difficult cancer to treat,” said Richard Gaynor, MD, vice president, product development and medical affairs for Lilly Oncology, in a statement. “If approved, necitumumab could be the first biologic therapy indicated to treat patients with squamous lung cancer.”
Necitumumab is a fully human IgG1 monoclonal antibody designed to block the ligand binding site of the human epidermal growth factor receptor (EGFR), which is a target in several anti-cancer treatments because it sparks cancer progression, both by promoting angiogenesis, or the formation of new blood vessels for tumors, and by inhibiting apoptosis, or cell death. Recently approved therapies for non-squamous NSCLC, including afatinib and erlotinib, target specific EGFR mutations, but those drugs are used to treat patients with nonsquamous histology.
In the phase III SQUIRE trial, 1093 patients with histologically or cytologically confirmed stage IV squamous NSCLC, who had received no prior therapy for metastatic disease, were randomized to receive one of two intravenously administered regimens. Patients in the experimental arm got first-line necitumumab at a dose of 800 mg on days 1 and 8 of every 3-week cycle in combination with gemcitabine at a dose of 1250 mg/m2
on days 1 and 8 of every 3-week cycle and cisplatin at a dose of 75 mg/m2
on day 1 of every 3-week cycle. Those in the control arm received a combination of gemcitabine and cisplatin at the same doses given in the experimental arm.
Necitumumab was being investigated in two separate phase III trials. The other study, the INSPIRE trial, was designed to compare necitumumab plus pemetrexed and cisplatin with pemetrexed and cisplatin alone. The study was discontinued in 2011 because of safety concerns over patients developing blood clots.
Lilly is also conducting a phase II study in which necitumumab in combination with paclitaxel and carboplatin is being evaluated in patients with stage IV squamous NSCLC. Previously, the drug had also been explored as a potential treatment for colorectal cancer and other solid tumors.