Novartis announced top-line results from its phase III ASCEND-4 clinical study for Zykadia (ceritinib) in patients with advanced anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC). The multicenter, randomized trial, which assessed the efficacy and safety of Zykadia in previously untreated adult patients, met its primary endpoint, demonstrating clinically significant improvement in progression free survival (PFS) compared to standard chemotherapy, including maintenance.

In addition to PFS, clinically meaningful results were achieved across key secondary efficacy measures, including objective response rate (ORR) and duration of response (DoR). The adverse events observed were consistent with the previously known adverse event profile of Zykadia. A full analysis of ASCEND-4 data along with detailed efficacy and safety results will be submitted for presentation at a major medical congress.

"Zykadia has proven to be an important treatment option for ALK+ NSCLC patients who have progressed following treatment with crizotinib," said Alessandro Riva, Global Head, Oncology Development and Medical Affairs, Novartis Oncology. "We are pleased to see these topline results show promise in untreated patients with advanced disease, and look forward to sharing these data with regulatory authorities in the coming months."

Of more than 1.8 million lung cancer diagnoses each year, approximately 2-7% of cases have the ALK gene rearrangement. These patients are candidates for treatment with a targeted ALK inhibitor.

ASCEND-4 was a phase III randomized, open label, multicenter global clinical trial to evaluate the safety and efficacy of Zykadia compared to standard chemotherapy, including maintenance, in adult patients with Stage IIIB or IV ALK+ NSCLC who received no prior therapy for their advanced disease.

The study was conducted at 203 clinical trial sites globally across 31 countries and randomized across 376 patients. Patients received Zykadia orally at 750 mg/daily or standard pemetrexed based platinum doublet chemotherapy per label (pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 or carboplatin AUC 5-6) including pemetrexed maintenance.

The primary endpoint of the trial was PFS by blinded independent review committee. Key secondary endpoints included: overall survival, PFS by investigator assessment, overall response rate, duration of response, disease control rate and time to response.

Zykadia is an oral, selective inhibitor of anaplastic lymphoma kinase (ALK), a gene that can fuse with others to form an abnormal "fusion protein" that promotes the development and growth of certain tumors in cancers including non-small cell lung cancer (NSCLC). Zykadia was granted conditional approval in the EU for the treatment of adult patients with ALK-positive advanced NSCLC previously treated with crizotinib. In the US, Zykadia was granted accelerated approval for the treatment of patients with ALK-positive metastatic NSCLC who have progressed on or are intolerant to crizotinib. Zykadia is currently approved in over 55 countries worldwide.

The most common adverse reactions with an incidence of >=10% were diarrhea, nausea, vomiting, tiredness (fatigue), liver laboratory test abnormalities (requires blood test monitoring), abdominal pain, decreased appetite, constipation, rash, kidney laboratory test abnormalities (requires blood test monitoring), heartburn and anemia. Grade 3-4 adverse reactions with an incidence of >=5% were liver laboratory test abnormalities, tiredness (fatigue), diarrhea, nausea and hyperglycemia (requires blood test monitoring).