Roche announced positive results from two pivotal studies (NP28673 and NP28761) that showed alectinib, its oral investigational anaplastic lymphoma kinase inhibitor (ALKi), shrank tumours (overall response rate; ORR: 50% and 47.8%, respectively) in people with advanced ALK-positive (ALK+) non-small cell lung cancer (NSCLC) whose disease had progressed following treatment with crizotinib.

In addition, alectinib was shown to shrink tumours in people whose cancer had spread to the central nervous system (CNS) (CNS ORR: 57.1% and 68.8%, respectively). Additionally, people whose tumours shrank in response to alectinib continued to respond for a median of 11.2 and 7.5 months, respectively (duration of response; DOR).

Alectinib demonstrated a safety profile consistent with that observed in previous studies. The most common adverse events (Grade 3 or higher occurring in at least 2% of people) were an increase in muscle enzymes (increased blood levels of creatine phosphokinase), increased liver enzymes and shortness of breath (dyspnea).

“Cancer spreads to the brain in about half of people with ALK-positive lung cancer, and these studies suggest that alectinib can shrink tumours in people with this difficult-to-treat disease,” said Sandra Horning, MD, chief medical officer and head of global product development. “We plan to submit these data to the FDA this year to support alectinib as a potential new option for people whose advanced ALK-positive lung cancer progressed on crizotinib.”

Results from both studies will be presented at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO).

Alectinib was granted Breakthrough Therapy Designation by the US Food and Drug Administration (FDA) in June 2013 for people with ALK+ NSCLC whose disease progressed on crizotinib. Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious diseases and to help ensure patients have access to them through FDA approval as soon as possible. Alectinib was made available in to patients in Japan in September 2014 and is marketed in Japan by Chugai Pharmaceutical, a member of the Roche Group.

ALEX, a global randomised phase III study, is ongoing, comparing alectinib to crizotinib as an initial (first-line) treatment for people with advanced NSCLC whose tumours were characterised as ALK+ by an investigational companion immunohistochemistry (IHC) test being developed by Roche.

NP28673 is a phase I/II global, single arm, open-label, multicentre trial evaluating the safety and efficacy of alectinib in 138 people with ALK+ NSCLC whose disease progressed on crizotinib.

The study showed by assessment of an independent review committee an ORR in 50.0% of people treated with alectinib, as measured by RECIST criteria.

An investigator assessment also showed tumours shrank in 47.8% of people who received alectinib.

CNS tumours shrank in response to alectinib in 57.1% of people whose disease had spread to the brain or other parts of the CNS.

In addition, the people whose tumours shrank in response to alectinib continued to respond for a median of 11.2 months (DOR, immature data).

The median progression-free survival (PFS) for people who received alectinib was 8.9 months.

Alectinib demonstrated a safety profile consistent with that observed in previous studies.

The most common (occurring in at least 2% of people) Grade 3 or higher adverse event was shortness of breath (dyspnea; 4%).

NP28761 is a phase I/II North American, single arm, open-label, multicentre trial evaluating the safety and efficacy of alectinib in 87 people with ALK+ NSCLC whose disease progressed on crizotinib.

The study showed by assessment of an independent review committee an ORR in 47.8% of people treated with alectinib, as measured by RECIST criteria.

An investigator assessment showed tumours shrank in 46.0% of people who received alectinib.

CNS tumours shrank in response to alectinib in 68.8% of people whose disease had spread to the brain or other parts of the CNS.

In addition, the people whose tumours shrank in response to alectinib continued to respond for a median of 7.5 months (DOR, immature data).

The immature median PFS was 6.3 months (95% confidence interval [CI] 5.5–not estimable).

Alectinib demonstrated a safety profile consistent with that observed in previous studies.

The most common (occurring in at least 2% of people) Grade 3 or higher adverse events were an increase in muscle enzymes (increased blood levels of creatine phosphokinase; 8%), increased liver enzymes (alanine aminotransferase; 6%, and aspartate aminotransferase; 5%) and shortness of breath (dyspnea; 3%).

Alectinib (RG7853/AF-802/RO5424802/CH5424802) is an investigational oral medicine created at Chugai Kamakura Research Laboratories and is being developed for people with NSCLC whose tumours are identified as ALK+. ALK+ NSCLC is often found in younger people who have a light or non-smoking history. It is almost always found in people with a specific type of NSCLC called adenocarcinoma.

Early studies with alectinib have shown activity on brain metastases, indicating that the drug may be taken up in the brain. The brain is protected by the Blood-Brain Barrier, a network of tightly joined cells that line the inside of the blood vessels in the brain and spinal cord. One of the ways the Blood-Brain Barrier prevents molecules from affecting the brain is to actively eject them from the barrier through a process known as ‘active efflux’. The active efflux system does not recognise alectinib, which means that it may travel into and throughout brain tissue.

The global phase 3 studies of alectinib include a companion test developed by Roche. Alectinib is marketed in Japan by Chugai Pharmaceutical, a member of the Roche Group.