The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion for Novartis drug Zykadia (ceritinib) to treat adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) previously treated with crizotinib. If approved in the European Union (EU), Zykadia will be the first treatment option to address an unmet medical need for patients with ALK+ NSCLC previously treated with crizotinib.

"Patients with advanced ALK+ NSCLC have few options when their cancer does not respond to currently approved therapy," said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. "As a leader in the development of precision oncology medicines, Novartis is committed to developing and bringing to market new treatments for patients with ALK+ NSCLC. This positive CHMP opinion for Zykadia brings us one step closer to providing the lung cancer community with new hope in the fight against this terrible disease."

Each year, there are 1.6 million people diagnosed with lung cancer, the leading cause of cancer death worldwide. The most common type of lung cancer is NSCLC, accounting for 85-90% of all cases. Of those, 2-7% are driven by a rearrangement of the ALK gene, which increases the growth of cancer cells and can be identified by a molecular test of the cancer tumor. Despite significant treatment advances for patients with ALK+ NSCLC, disease progression is often inevitable and more treatment options are needed.

In the EU, the European Commission generally follows the recommendations of the CHMP and delivers its final decision within three months of the CHMP recommendation. The decision will be applicable to all 28 EU member states plus Iceland, Norway and Liechtenstein. Zykadia is currently approved in the United States, Mexico, Chile, South Korea, Guatemala and Ecuador. Additional regulatory reviews are underway in North America, South America, Central America and Asia.

The CHMP recommendation for Zykadia was based on results from two global, multicenter, open-label, single-arm studies (Study A and Study B). Comparative efficacy data from randomized clinical studies are not yet available. The primary efficacy endpoint for these studies was overall response rate (ORR), including complete response and partial response, for patients who were treated with a 750 mg dose of Zykadia, confirmed by repeat assessments performed not less than four weeks after the criteria for response was first met. Additional evaluations included duration of response (DOR) and progression-free survival (PFS) by investigator and blinded independent review committee (BIRC) assessment, and overall survival (OS). Tumor evaluations were performed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 in Study A and RECIST 1.1 in Study B.

Study A was a phase I study that included a dose-escalation phase and an expansion phase, at the recommended dose of 750 mg. The study evaluated a total of 246 ALK+ NSCLC patients who were treated with 750 mg of Zykadia: 163 had received prior treatment with an ALK inhibitor and 83 were ALK inhibitor-naïve. In patients who had previously received treatment with an ALK inhibitor, the ORR was 56.4% [95% CI, 48.5-64.2%], the median DOR was 8.3 months [95% CI, 6.8-9.7 months] and the median PFS was 6.9 months [95% CI, 5.6-8.7 months] based on investigator assessment.

Study B was a phase II study designed to evaluate the efficacy and safety of 750 mg Zykadia in patients with locally advanced or metastatic ALK+ NSCLC. Study B involved 140 patients who had been previously treated with one to three lines of chemotherapy followed by treatment with crizotinib, and who had then progressed on crizotinib.

In Studies A and B, brain metastases at baseline were seen in 60.1% and 71.4% of patients who had received prior treatment with an ALK inhibitor, respectively. The ORR, DOR and PFS (by BIRC assessment) for patients with brain metastases at baseline were similar with those reported for the overall population of these studies.

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

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 is currently approved in the United States, Mexico, Chile, South Korea, Guatemala and Ecuador to treat adult patients with ALK+ NSCLC. Additional regulatory reviews are underway in North America, South America, Central America and Asia.

In the European Union, Zykadia (ceritinib) is an investigational agent and has not been approved by regulatory authorities.