November 18, 2014
By Riley McDermid, BioSpace.com Breaking News Editor
Biotech giant GlaxoSmithKline LLC will partner with scrappy Clovis Oncology, Inc. on a new Phase 1/2 trial of an experimental oral combination therapy targeting mutant epidermal growth factor receptor (EGFR) in non-small cell lung cancer, the companies said Tuesday.
The trial to test the combo of rociletinib and trametinib is planned for the first half of 2015. It will primarily test the safety and activity of the combination in patients with EGFR mutant NSCLC who were previously treated with an EGFR tyrosine kinase inhibitor (TKI).
“We have seen significant activity in EGFR mutant NSCLC patients treated with rociletinib monotherapy, and so an important next step in our research is to examine rociletinib in combination with other targeted therapies that may also impact acquired resistance to EGFR inhibitors,” said Lecia Sequist, the lead investigator for the study and medical doctor at Massachusetts General Hospital Cancer Center and associate professor of Medicine at Harvard Medical School.
All patients with EGFR mutant NSCLC eventually develop resistance to EGFR TKI therapy, said Boulder, Colo.-based Clovis, with the T790M gene usually the primary resistant mutation, cropping up in 60 percent of patients treated with first- and second-generation EGFR inhibitors.
Rociletinib is designed to target the T790M and the activating mutations of EGFR (L858R and Del19). So far, it has shown some success in clinical activity and tolerability in Phase 1/2 studies of patients with EGFR mutant NSCLC. Trametinib inhibits mitogen-activated protein kinase (MEK), which determines MAPK pathway signaling, thus inhibiting growth factor-mediated signaling and cellular proliferation.
Combining the two shows an enormous amount of potential, said executives at Clovis on Tuesday.
“As we continue to see compelling activity for rociletinib single-agent therapy at our selected dose, we look forward to exploring combination trials in both T790M-positive and T790M-negative patients,” said Patrick Mahaffy, president and CEO of Clovis Oncology. “We believe that given the tolerability profile of rociletinib, particularly its lack of cutaneous toxicity, it may be a good candidate for combination therapy with trametinib, and other relevant targeted therapies. We intend to announce additional combination studies over the next few months.”
Trametinib has been approved by the U.S. Food and Drug Administration as a single agent for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations.
