GlaxoSmithKline (GSK) and Clovis Oncology, Inc., a biopharmaceutical company based in Boulder, Colorado, have entered into a clinical trial collaboration to evaluate a combination therapy targeting mutant epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC). The Phase I/IItrial of Clovis’ rociletinib given in combination with GSK’s trametinib is planned to start in the first half of 2015.

The trial is designed to assess the safety and activity of the combination in patients with EGFR mutant NSCLC who were previously treated with an EGFR tyrosine kinase inhibitor (TKI). Rociletinib is an oral, potent, mutant-selective inhibitor of EGFR under investigation for the treatment of EGFR-mutated NSCLC. Rociletinib targets the activating mutations to EGFR (L858R and Del19), while also inhibiting the primary resistance mutation, T790M, which develops in 60% of patients treated with first- and second-generation EGFR inhibitors. In May of 2014, the US Food and Drug Administration granted Breakthrough Therapy designation for rociletinib as treatment for mutant NSCLC in patients with the T790M mutation after progression on EGFR-directed therapy.

Trametinib is a MEK inhibitor which blocks the activity of a protein kinase called MEK. This protein is present in the MAPK pathway, which regulates the normal growth and death of cells and plays a role in metastatic melanoma development. Some mutations in the BRAF gene can cause the MEK protein to stimulate cancer cell growth and survival, therefore, inhibiting MEK can potentially slow down the growth of tumors in BRAF-mutant metastatic melanoma.

Source: Clovis Oncology