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AZ pushes immuno-oncology duo into phase III

MEDI4736 and tremelimumab achieved disease control in 48% of NSCLC patients

AstraZeneca AZ headquarters London UK 

AstraZeneca (AZ) has reported positive results from a phase Ib clinical trial of MEDI4736 and tremelimumab in lung cancer at ASCO and says it will now take the immuno-oncology combination into pivotal testing.

The combination of PD-L1 inhibitor MEDI4736 and tremelimumab - a CTLA4 inhibitor - showed clinical activity in patients with advanced non-small cell lung cancer (NSCLC), achieving disease control in 48% of patients.

MEDI4736 and tremelimumab both target mechanisms by which tumour cells evade detection by the immune system and work via a similar mechanism to the combination of Bristol-Myers Squibb Opdivo (nivolumab) and Yervoy (ipilimumab), which was shown to have a high level of efficacy in melanoma at ASCO.

Importantly, the data showed that the combination was effective not only in advanced NSCLC patients who expressed PD-L1 - around a third of all NSCLC patients - but also in PD-L1-negative cases who are less likely to respond to monotherapy with PD1/PD-L1-targeting drugs.

All told, MEDI4736 and tremelimumab achieved a 27% overall response rate in PD-L1-negative patients, which AZ indicated was a good result given that a range of doses was being tested to identify the best regimen to take forward into phase III trials.

AZ has already decided on the design of the MEDI4736/tremelimumab study in NSCLC, which will be called ARCTIC and focus exclusively in PD-L1-negative patients, who are "in need of better treatments," according to Ed Bradley, head of oncology at AZ's Medimmune unit.

Links with Lilly

Meanwhile, in amongst the clinical data coming out of the ASCO conference, AZ and Eli Lilly unveiled a joint research programme in solid tumours that will see MEDI4736 tested alongside Cyramza (ramucirumab), Lilly's fast-growing VEGFR2 antagonist.

Cyramza works by blocking the development of the blood supply that helps fuel tumour growth and is already approved to treat NSCLC as well as colorectal and gastric/gastroesophageal junction cancer. 

AZ and Lilly have not revealed which solid tumours will be the focus of their collaboration, or the financial terms of the alliance, but said Lilly would be responsible for an initial phase I trial of the combination to establish safety and dosing.

Lilly also has an agreement in place with Merck & Co to test Cyramza alongside its PD-1 inhibitor Keytruda (pembrolizumab).

Meanwhile, AZ has been chalking up multiple alliances on MEDI4736 with other cancer drug developers - including Celgene, Immunocore, Johnson & Johnson (J&J)  - amid a growing recognition that cocktails of the immuno-oncology drugs with other cancer therapeutics provide better efficacy.

"We believe the most powerful combinations will likely target multiple mechanisms in the immune system where cancer wages its battles – T-cell activation, antigen presentation and innate immunity, and the tumour microenvironment," commented Medimmune executive vice president Bahija Jallal.

Article by
Phil Taylor

1st June 2015

From: Research



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