By Turna Ray
Almac and Lilly UK are developing a companion diagnostic to gauge which patients with non-squamous non-small cell lung cancer will benefit from treatment with Alimta and cisplatin combination therapy.
The collaboration partners will conduct a Phase II study to evaluate whether the biomarker thymidylate synthase can predict which lung cancer patients will benefit when treated with the Alimta/cisplatin regimen.
The large, multi-center, single-arm Phase II study will involve patients diagnosed at stage IIIB/IV non-squamous NSCLC. "The final endpoint will be the development of a companion diagnostic test that will select patients likely to benefit from treatment with Alimta," Almac said in a statement.
In the US, Alimta (pemetrexed) is approved by the Food and Drug Administration in combination with cisplatin for the initial treatment of advanced non-squamous NSCLC. The combination regimen is not indicated for patients with squamous cell NSCLC.
Alimta's label notes that the drug inhibits folate-dependent enzymes, such as thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. Once Alimta reaches human cells, the drug is "converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase," the label notes. According to the label, the polyglutamate forms are retained more readily in tumor cells and are inhibitors of TS and GARFT.
"Polyglutamated metabolites are thought to have an increased intracellular half-life resulting in prolonged drug action in malignant cells," the label states.
During the Phase II study, Almac will perform global gene-expression profiling, microRNA profiling, SNP genotyping, and qPCR validation as well as perform the data analysis for the study. The company also plans to conduct parallel exploratory analyses to develop alternate strategies for personalizing Alimta treatment using novel predictive biomarkers.
Gene expression profiling in Lilly's study will be done on formalin-fixed paraffin-embedded samples using Almac's Diagnostics Lung Cancer Disease-Specific Array research tool.
The Lung Cancer DSA combines Almac's in-house sequencing and data mining technologies. Almac claims the product "is the first microarray based on the transcriptome of an individual disease," and will allow Lilly to get more targeted gene expression data than previously available on generic arrays.
Like the lung cancer research tool, Almac has a line of cancer research tools under the DSA brand, all using high-density transcriptome-based microarrays, as well as FFPE and frozen samples, which it uses to help drug companies gather additional information in clinical trials for prostate, lung, ovarian, breast, and colorectal cancers.
This is Almac's second research collaboration with a large pharmaceutical company in the last six months using its Cancer DSA research tool.
In May, Almac announced that Pfizer and the PETACC3 Translational Research Working Party were using its Colorectal Cancer DSA platform to identify molecular subtypes in colorectal cancer and to identify new drug targets in treatment-resistant patients [see PGx Reporter 05-20-2009].
The platform is being used to conduct gene expression profiling on FFPE tumor samples from the Pan-European Trials in Adjuvant Colon Cancer (PETACC 3) trial. Pfizer, which manufactures the colorectal cancer drug irinotecan under the brand name Camptosar, will use the resulting research and data from the Almac collaboration for drug development purposes, a spokesperson for Almac told Pharmacogenomics Reporter at the time.
With regard to the collaboration with Lilly UK, it is not immediately clear whether the deal is only for the European market, and whether Almac intends to seek marketing approval for a potential companion diagnostic from the US Food and Drug Administration.
Almac refused to provide additional information on its companion diagnostics collaboration with Lilly.