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Trial results show treatment-resistant advanced non-small cell lung cancer responds to new drug, rociletinib

A new drug that targets not only common cancer-causing genetic mutations in patients with non-small cell lung cancer (NSCLC), but also a form of the mutation that causes resistance to treatment, has shown promising results in patients in a phase I/II clinical trial. The research will be presented at the 26th EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain.

Approximately 10-15% of Caucasian and 30-35% of Asian patients with NSCLC have a mutation in the epidermal growth factor receptor (), which can be successfully targeted with inhibitors called tyrosine kinase inhibitors (TKI), such as erlotinib, gefitinib and afatinib [2]. However, these patients will eventually develop resistance to EGFR TKI therapy and a further EGFR mutation called T790M accounts for 60% of this acquired resistance.

Professor Jean-Charles Soria, Chairman of the Drug Development Department at Gustave Roussy Cancer campus, France, will tell the Symposium: “Currently, there are no approved targeted therapies for mutant EGFR lung cancer patients who develop the T790M mutation, which means their disease inevitably will get worse. Rociletinib (CO-1686) is a new and potent oral designed to selectively target both the initial activating EGFR mutations as well as the T790M resistance mutation. This compound spares normal (wild-type) EGFR and this means that it causes far fewer toxic side-effects than other EGFR inhibitors. Therefore, it may benefit patients both as a first-line and second- or later-line treatment, by producing a durable clinical benefit and with a reduced toxicity profile compared to current therapies. Current TKIs inhibit the normal EGFR as well as the mutant EGFR, causing acne-like skin rashes and paronychia – an inflammation of the folds of tissue around finger and toe nails – both of which can be very troublesome for patients.”

Patients with advanced NSCLC with the EGFR mutation, with or without the T790M resistance mutation, were enrolled in the phase I/II clinical trial in centres in Europe, Australia and the USA; enrolment of patients for the phase I part of the study began in March 2012, and for the phase II part in August 2013. The phase I portion of the study examined two formulations and multiple doses and schedules of rociletinib; 625mg twice a day continuously of hydrobromide (HBr) salt tablet form of rociletinib was identified as the pivotal dose, schedule and formulation for the phase II part of the study.

By October 2014, 179 patients had been treated at therapeutic doses (either 900mg twice a day of freebase formulation, or 500mg or more twice a day of HBr salt tablet). Preliminary results for all of these patients (those with and without the T790M and T790M resistance mutation) include an overall response rate of 46% and a disease control rate of 84%.