Selective ALK inhibitor shows NSCLC promise
medwireNews: Preliminary trial results suggest that a novel, highly selective ALK inhibitor may be effective for the treatment of advanced non-small-cell lung cancer (NSCLC) in Japanese patients with the ALK rearrangement.
As reported in The Lancet Oncology, phase I findings from 24 Japanese patients show that an oral dose of the agent CH5424802 up to 300 mg twice daily was well tolerated without any dose-limiting toxicity or grade 4 adverse events over at least two 21-day cycles.
Moreover, phase II results for CH5424802 at 300 mg twice daily reveal an objective response in 43 (93.5%) of 46 Japanese patients, including a complete response in two (4.3%) patients and a partial response in 41 (89.1%) patients. Of the other three patients, one (2.2%) had stable disease and two (4.3%) had an unknown response due to early withdrawal but there were no reports of disease progression.
Tumor response occurred early in treatment, with 65% achieving a partial response within the first cycle and 87% within two cycles of treatment.
In all, 87% of patients were still receiving treatment at time of data cutoff, after a median of 7.1 months of treatment and a median follow up of 7.6 months.
Fifteen (33%) patients had known brain metastases, seven of whom achieved disease control for more than 6 months, and there were no reports of central nervous system progression at time of data cutoff.
There was no significant correlation between disease response and age, gender, performance status, body mass index, prior chemotherapy for metastasis, prior use of pemetrexed, type of ALK test, or brain metastasis status, add Tomohide Tamura (National Cancer Center Hospital, Tokyo, Japan) and co-authors.
As ALK expression is extremely low in adult tissues, the researchers believe that the high selectivity of CH5424802 may minimize side effects.
All patients reported treatment side effects, with 17 (37%) patients experiencing grade 3 events, but there were no reports of grade 4 events, and no deaths. Serious events occurred in five (11%) patients and four (9%) patients discontinued treatment due to brain edema, tumor bleeding, interstitial lung disease, or sclerosing cholangitis, with all but edema thought to be related to CH5424802 use.
"The high proportion of patients achieving an objective response and the favourable effects on brain metastases suggest that CH5424802 is a promising ALK inhibitor," the researchers conclude.
Further investigation is now undergoing to determine whether CH5424802 is as effective in other patient populations, including non-Asian patients and those who are resistant to the ALK inhibitor crizotinib.
medwireNews (www.medwirenews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013
By Lynda Williams, Senior medwireNews Reporter