AstraZeneca builds case for adding savolitinib to Iressa, Tagrisso

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AstraZeneca has posted preliminary phase 1b/2 data on the use of savolitinib in combination with Iressa or Tagrisso. Adding the MET tyrosine kinase inhibitor (TKI) to the approved drugs triggered partial responses in a significant minority of NSCLC patients who had progressed after treatment with an EGFR-TKI.

Across two separate trials, AstraZeneca and Hutchison China MediTech (Chi-Med) are giving 600 mg of savolitinib to patients with EGFR-mutant, MET-amplified NSCLC. The rationale is that savolitinib, as an inhibitor of MET, may improve outcomes in patients who develop resistance to, or are innately resistant to, EGFR-TKIs as a result of MET amplification. 

One study had enrolled and treated 45 patients as of the mid-April cutoff. These patients received the daily dose of savolitinib on top of AstraZeneca’s Tagrisso. Of the 25 subjects who had already been treated with a third-generation EGFR-TKI, such as Tagrisso, five had partial responses. 

That 20% response rate was bested by the cohort that had not been treated with third-generation EGFR-TKIs. In this group, more than 40% of patients had partial responses. The response rate was unaffected by whether the patients had EGFR T790M resistance mutations.

The other study is giving savolitinib in combination with Iressa, a first-generation EGFR-TKI. That trial had treated 44 NSCLC patients by the March cut-off point. Eleven patients experienced confirmed partial responses. The study team is awaiting confirmation of response in a further four patients. That means the partial response rate could ultimately hit 34%.

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Collectively, the data have encouraged people involved in the trial that savolitinib can play a role in tackling drug-resistant lung cancer. 

“Secondary resistance mechanisms often emerge during treatment with mutation-targeted medicines, leading to disease progression. The data presented at WCLC demonstrate the potential of utilizing savolitinib in c-MET-driven lung cancers to address resistance challenges,” Samsung Medical Center’s Myung-Ju Ahn, M.D. said in a statement. 

AstraZeneca needs savolitinib to live up to that potential to bolster a key franchise. Iressa took years to find its market but AstraZeneca understood the genetics of NSCLC better by the time it came to develop Tagrisso. AstraZeneca is hoping that will lead the drug to sales of $3 billion a year. 

If savolitinib can corner another step in the NSCLC treatment pathway, the overall franchise could ease past that figure, giving succor to AstraZeneca following the faltering of its immuno-oncology plans.