Alectinib Approved by FDA for ALK-Positive NSCLC

December 11, 2015

Alectinib has been granted accelerated approval by the FDA in patients with metastatic ALK-positive non-small cell lung cancer (NSCLC) following progression on crizotinib.

Richard Pazdur, MD

Alectinib (Alecensa) has been granted accelerated approval by the FDA in patients with metastatic ALK-positive non—small cell lung cancer (NSCLC) following progression on crizotinib (Xalkori). The approval was based on objective response rates (ORR) seen in two phase II clinical trials.

“Today’s approval provides a new therapy for a group of patients who would have few treatment options once their disease no longer responds to treatment with Xalkori,” Richard Pazdur, MD, director, Office of Hematology and Oncology Products, FDA Center for Drug Evaluation and Research, said in a statement. “In addition to the primary effect on tumors in the lung, Alecensa clinical trials provide evidence of an effect on tumors that had spread to the brain, which is an important effect for clinicians to understand.”

In the first study, labeled NP28761, the ORR with alectinib was 38% by independent review and 46% by investigator assessment. The duration of response was 7.5 months.

In the second trial, known as NP28673, ORR was 44% by indendent review and 48% by investigator assessment. The duration of response was 11.2 months.

In NP28673, crizotinib-pretreated patients received alectinib at 600 mg orally twice daily until progression. One hundred twenty-two patients were evaluable for response. The median age of patients was 51.6 years and 60% had baseline CNS metastases. Most patients (80%) had received prior chemotherapy.

The second pivotal phase II study, NP28761, was an open-label, single-arm, multicenter trial that included 87 patients with ALK-positive NSCLC who progressed on crizotinib. As in NP28673, patients received alectinib at 600 mg orally twice daily until progression.

In a combined analysis of the two studies, the ORR in patients with CNS metastases was 61% (95% CI, 46-74). The CNS complete response rate was 18%. The duration of response in the CNS was 9.1 months.

“Alecensa is now approved as a new option for people with ALK-positive NSCLC who progress on or are intolerant to crizotinib,” Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech, the company developing the drug, said in a statement. “Sixty percent of people enrolled in our studies had tumors that had spread to their central nervous systems, and Alecensa shrank tumors in many people in a subset of patients with CNS disease.”

The accelerated approval is contingent upon results from a confirmatory analysis. The phase III ALEX study is meant to support this approva. In this trial, alectinib is being compared with crizotinib for chemotherapy-naive patients with ALK-positive NSCLC. The study hopes to enroll 286 patients, with early results expected in 2018.

In 2013, alectinib received a breakthrough therapy designation from the FDA as a treatment for patients with ALK-positive NSCLC following progression on crizotinib. Alectinib was approved in Japan in 2014, under the name Alecensa, for patients with ALK-positive NSCLC.