FDA Grants Zykadia Breakthrough Designation for Lung Cancer

The FDA recently accepted a supplemental new drug application for the expanded use of ceritinib (Zykadia) to treat lung cancer, and also granted the application priority review.

Novartis is seeking regulatory approval for ceritinib as a first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC), whose tumors are anaplastic lymphoma kinase (ALK)-positive, according to a press release.

The drug was also granted breakthrough therapy for patients with ALK+ metastatic NSCLC with metastases in the brain.

The new submission for ceritinib was based on positive results from the phase 3 ASCEND-4 clinical trial, which explored the safety and efficacy of the drug compared with platinum-based chemotherapy. Included in the clinical trial were 376 patients with stage 3B or 4 ALK+ NSCLC.

Patients were randomized to receive daily treatment with ceritinib 750 mg or standard chemotherapy for 4 cycles followed by pemetrexed maintenance therapy. Novartis reported that 60% of patients with brain metastases did not receive prior treatment with radiation therapy.

The investigators found that patients treated with ceritinib had a median progression-free survival (PFS) of 16.6 months, compared with 8.1 months for first-line treatment with pemetrexed-platinum chemotherapy with pemetrexed maintenance, according to Novartis. There was also a 45% risk reduction in PFS associated with ceritinib treatment.

A PFS of 26.3 months was observed with ceritinib treatment in patients without brain metastases, compared with 8.3 months among these patients treated with chemotherapy.

In patients with brain metastases, the investigators found a PFS of 10.7 months in the ceritinib cohort, compared with 6.7 months in the chemotherapy cohort. Intracranial overall response rate (ORR) was discovered to be in line with whole body ORR, according to the press release.

Common adverse events associated with ceritinib were diarrhea, nausea, vomiting, alanine aminotransferase increase, aspartate aminotransferase increase, gamma-glutamyltransferase increase, decreased appetite, blood alkaline phosphate increase, and fatigue, Novartis reported.

Breakthrough therapy designation is granted if a treatment has shown promise to offer significant benefits over current treatments. The latest breakthrough therapy designation for ceritinib as a first-line therapy for patients with ALK+ NSCLC with brain metastasis marks the second time the drug has received the designation.

Currently, ceritinib is approved to treat patients with ALK+ metastatic NSCLC who have progressed on, or are tolerant to crizotinib.

"We are committed to advancing our understanding of mutation-driven lung cancer, where there continues to be significant unmet need," said Vas Narasimhan, global head Drug Development and chief medical officer, Novartis. "Today's Priority Review of [ceritinib] for newly diagnosed patients with ALK+ metastatic NSCLC, including Breakthrough Therapy designation for those with brain metastases, brings us closer to delivering the right treatment to the right patient at the right time."