FDA Approves Alecensa for Subset of Patients With NSCLC


The agent was approved as a treatment for patients with metastatic ALK-positive non-small cell lung cancer (NSCLC).

The FDA has granted an accelerated approval to Alecensa (alectinib) as a treatment for patients with metastatic ALK-positive non—small cell lung cancer (NSCLC) following progression on Xalkori (crizotinib), based on objective response rates (ORR) in two phase 2 clinical trials.

In the first study, labeled NP28761, the ORR with Alecensa was 38 percent by independent review and 46 percent by investigator assessment. The duration of response was 7.5 months. For the second trial, known as NP28673, the ORR was 44 percent by independent review, 48 percent by investigator assessment, and the duration of response was 11.2 months.

“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, director of the Office of Hematology and Oncology Products in the FDA’s 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.”

NP28761 was an open-label single-arm multicenter trial that included 87 patients with ALK-positive NSCLC who progressed on Xalkori. In this study, which was conducted in North America, patients received Alecensa at 600 mg orally twice daily until progression.

In data presented during the 2015 American Society of Clinical Oncology Annual Meeting,1 patients with central nervous system (CNS) metastases treated with Alecensa experience an ORR of 68.8 percent by independent review with Alecensa. Additionally, median progression-free survival (PFS), although not yet mature, was 6.3 months.

In second pivotal phase 2 study, NP28673, Xalkori-pretreated patients received Alecensa at 600 mg orally twice daily until progression. One hundred thirty-eight patients were evaluable for response. The median age of patients was 51.6 years and 60 percent had baseline CNS metastases. Most patients (80 percent) received prior chemotherapy.

In data published in the Journal of Clinical Oncology,2 the median independently-reviewed PFS was 8.9 months. In 35 patients with CNS disease, the ORR was 57 percent and the duration of response was 10.3 months.

A pooled analysis of the two studies was conducted for 51 patients with CNS metastases. Across the studies, 69 percent of patients had received prior brain radiation, with nearly half of patients completing radiation (49 percent) at least six months prior to receiving Alecensa.

In this analysis, the ORR in patients with CNS metastases was 61 percent. In this same group, the CNS complete response rate was 18 percent and the duration of response was 9.1 months. The most common adverse events (AEs) associated with Alecensa across the two studies were fatigue, constipation, edema and myalgia. Serious AEs included liver problems, severe or life-threatening inflammation of the lungs, very slow heartbeats and severe muscle problems. Additionally, the FDA noted that Alecensa was associated with photosensitivity and an increased risk of sunburn.

The most frequently observed AEs of at least grade 3 were increased creatine phosphokinase (4.6 percent), dyspnea (3.6 percent), increased aspartate transaminase (3.6 percent), increased alanine transaminase (4.8 percent), hyperbilirubinemia (2.4 percent), hyperglycemia (2 percent), hypokalemia (4 percent), hypophosphatemia (2.8 percent), hyponatremia (2 percent), anemia (2 percent) and lymphopenia (4.6 percent).

“Alecensa is now approved as a new option for people with ALK-positive NSCLC who progress on or are intolerant to [Xalkori],” Sandra Horning, 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, which the phase 3 ALEX study is meant to provide. In this trial, Alecensa is being compared with Xalkori for chemotherapy-naive patients with ALK-positive NSCLC. The study hopes to enroll 286 patients, with early results expected in 2018.

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


  1. Gandhi L, Shaw AT, Gadgeel SM, et al. A phase II, open-label, multicenter study of the ALK inhibitor alectinib in an ALK+ non-small-cell lung cancer (NSCLC) U.S./Canadian population who had progressed on crizotinib (NP28761). J Clin Oncol. 2015;33 (suppl; abstr 8019).
  2. Ou S-HI, Ahn JS, Petris LD, et al. Alectinib in Crizotinib-Refractory ALK-Rearranged Non—Small-Cell Lung Cancer: A Phase II Global Study [Published online November 23, 2015]. J Clin Oncol. doi: 10.1200/JCO.2015.63.9443
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