Clovis set for showdown with AZ in lung cancer

Clovis Oncology has reported positive phase II results with lung cancer drug rociletinib that sets up a filing in mid-2015 – around the same time as AstraZeneca’s rival drug AZD9291.

Interim data from the US company’s study reported this week show that rociletinib (CO-1686) achieved a 67 per cent objective response rate (ORR) in heavily pre-treated patients with non-small cell lung cancer (NSCLC), with a median progression-free survival (PFS) of more than 10 months.

For comparison, NSCLC patients who have failed targeted therapies and are then treated with chemotherapy typically have a PFS of 2.8 months and an overall response rate of around 13 per cent. The data are due to be presented at the ENA medical symposium in Barcelona later this week.

Like AZD9291, rociletinib combines epidermal growth factor receptor (EGFR) inhibition with activity against the T790M mutation, which accounts for more than half of all cases of resistance to EGFR inhibitors.

While current EGFR tyrosine kinase inhibitors such as AZ’s Iressa (gefitinib) and Genentech/Astellas’ Tarceva (erlotinib) can achieve good responses in EGFR-positive tumours, once resistance develops patients have few treatment options available.

The unmet need in this group of patients has resulted in lofty sales expectations for drugs that can address the problem. AZ has said it expects AZD9291 to eventually grow into a $3 billion-a-year product and at its latest strategic update indicated it would file for approval of the drug in the US in the first half of 2015.

Interestingly, Clovis’ trial suggests that rociletinib also seems to have activity in patients without the T790M mutation, with a 36 per cent ORR and median PFS of 7.5 months in this group, which could support the use of the drug in first-line NSCLC treatment, according to trial investigator Jonathan Goldman of UCLA.

That finding “is surprising and may address a remaining unmet medical need for this additional group of patients who have also progressed on initial … therapy,” he added.

Clovis also has a phase II/III trial called TIGER-1 comparing rociletinib to Tarceva as a front-line therapy in newly-diagnosed, EGFR-positive NSCLC patients, according to chief executive Patrick Mahaffy.

Meanwhile the company is currently recruiting patients into TIGER-2 – which involves T790M-positive patients who have received just one prior EGFR inhibitor – and will shortly start an ‘all-comer’ trial in NSCLC that will compare rociletinib to chemotherapy in both T790M-positive and negative patients.

An extension phase of the ongoing phase II trial – called TIGER-X – will be combined with data from TIGER-2 and form the basis of regulatory submissions in the US and EU.

Image: Shutterstock / decade3d

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