Pfizer has made a splash at the 46th Annual American Society of Clinical Oncology (ASCO) meeting in Chicago with early but impressive data on its targeted ALK inhibitor crizotinib in non-small cell ling cancer (NSCLC).

Results to date from an expansion cohort of a Phase I/II trial evaluating crizotinib (PF-02341066) in patients with advanced NSCLC carrying the ALK (anaplastic lymphoma kinase) fusion gene showed that at eight weeks, 87% of patients given crizotinib had responded to treatment, with 57% of those experiencing tumour shrinkage.

“Many of these patients had received three or more prior treatments, and we would expect only about 10% to respond,” commented lead study author Dr Yung-Jue Bang, professor in the Department of Internal Medicine at Seoul National University College of Medicine in Seoul, Korea.

“These results are quite dramatic and represent an important improvement over what we would see with standard chemotherapy for patients with metastatic disease,” he added.

Taken orally, crizotinib is a selective small-molecule inhibitor of the ALK and MET/HGF receptor tyrosine kinases.

In patients with the ALK gene alteration targeted in the Pfizer study, the fusion of ALK and another gene, echinoderm microtubule-associated protein like-4 (EML4), promotes lung cancer cell growth by encoding the production of anaplastic lymphoma kinase, a tumour-specific protein.

Alterations in the ALK gene have been identified as an important factor in cancers such as NSCLC, neuroblastomas and rare sarcomas, Pfizer notes. EMLA-ALK fusion oncogenes are reported in around 4% of NSCLC cases. Worldwide, around 45,000 newly diagnosed NSCLC patients per year are estimated to be ALK-positive.

Pfizer has already started an open-label, randomised Phase III trial (PROFILE 1007) comparing crizotinib with standard-of-care chemotherapy in the treatment of ALK-positive recurrent NSCLC. Also underway is a Phase II open-label, single-arm trial (PROFILE 1005) of crizotinib in similar patients who have received more than one line of prior chemotherapy.

This is an area of significant unmet medical need. The current five-year survival rate for NSCLC patients in the advanced setting is less than 10%, Pfizer points out.

The company has partnered with Abbott Molecular to develop a diagnostic test that can screen patients with NSCLC for the presence of ALK gene alterations.