Novel ALK TKI shows promise in NSCLC

CHICAGO — A novel anaplastic lymphoma kinase tyrosine kinase inhibitor was associated with encouraging response and safety outcomes in a cohort of patients with non–small cell lung cancer, according to study results presented at the ASCO Annual Meeting.

The multicenter study evaluated LDK378 (Novartis) in 131 patients with advanced NSCLC harboring a genetic alteration in ALK.

The cohort included 123 patients who had ALK-rearranged NSCLC as determined by FISH. More than 20 of the patients had progressed during or after treatment with crizotinib (Xalkori, Pfizer).

LDK378 was administered orally once daily at doses of 50 to 750 mg. There were 59 patients in whom the maximum tolerated daily dose of 750 mg was established, and 72 patients were included in an expanded cohort at this dose. 

The researchers assessed patients for pharmacokinetics, response to therapy and adverse events.

The current report includes data through Nov. 8,  2012.

The overall response rate was 70% among 88 evaluable patients with NSCLC who received the study drug at a dose of 400 mg to 750 mg daily. There were 40 confirmed responses and 22 unconfirmed responses in this group.

Researchers reported a 73% overall response rate in the crizotinib-resistant subset (n=64). Thirty-one confirmed responses and 16 unconfirmed responses were reported in this group.

Fifty percent of unconfirmed responses were ongoing through November 2012.

Patients with and without crizotinib resistance experienced responses, as did patients with untreated metastases in the central nervous system.

The median duration of response was 7.4 months (95% CI, 6.7-not reached) in the confirmed response group of patients with NSCLC. Seventy-eight percent of those patients demonstrated a duration of response ≥6 months.

A median PFS of 8.6 months (95% CI, 4.3-19.3) was reported among the 123 NSCLC patients.

The most frequent adverse events were nausea (72%), diarrhea (69%), vomiting (50%) and fatigue (31%).

ALT was the most common grade 3/4 event (12%). Grade 3/4 diarrhea occurred in 7% of patients, and AST elevation occurred in 6%.

“These results confirm that LDK378 has activity in patients with ALK-positive NSCLC, including those who have progressed on crizotinib, as well as those who haven’t taken crizotinib,” lead investigator Alice T. Shaw, MD, PhD, of Massachusetts General Hospital Cancer Center in Boston, said in a press release. “LDK378 may become another standard targeted therapy for these ALK-positive patients.”

For more information:

Shaw AT. #8010. Presented at: ASCO Annual Meeting; May 31-June 4, 2013; Chicago.

Disclosure: The researchers report research funding and employment relationships with Novartis, as well as consultant or advisory roles with ARIAD, Boehringer Ingelheim, Chugai Pharma, Lilly, Novartis, Pfizer and Roche.