AstraZeneca dumps phase 3 renal cell carcinoma program

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AstraZeneca CEO Pascal Soriot (AstraZeneca)

AstraZeneca has scrapped development of savolitinib as a monotherapy treatment for papillary renal cell carcinoma (PRCC). The phase 3 program was one of five projects removed from AstraZeneca’s pipeline (PDF) in conjunction with its second-quarter results.

Working with partner Hutchison China MediTech (Chi-Med), AstraZeneca began comparing the MET inhibitor to Pfizer’s Sutent in a phase 3 PRCC trial in 2017. The trial reached its primary completion date in August, but by then hopes for a positive outcome had already wilted in light of data generated in another study.

Late last year, Chi-Med said savolitinib was unlikely to beat Sutent in first-line MET positive PRCC, the target population of the Savoir phase 3. Chi-Med based that prediction on the findings of a molecular epidemiology study that found Sutent was effective in first-line PRCC regardless of MET status. The analysis showed Sutent is heavily used as a first-line treatment and rarely later in the pathway.

AstraZeneca and Chi-Med responded by stopping enrollment in the trial at 60 patients, well short of the 180 subjects they originally planned to recruit. The drastic action reflected the reduced chances of success in the first-line setting and the conclusion that the minimal use of Sutent as a second-line treatment would make it operationally impractical to target a different patient population. 

Today, AstraZeneca confirmed savolitinib has reached the end of the line as a monotherapy treatment for PRCC by removing the phase 3 from its pipeline. AstraZeneca and Chi-Med continue to test the drug in other settings, both as a monotherapy and in combination with other medicines. 

The savolitinib phase 3 was one of five programs removed from AstraZeneca’s clinical pipeline in its latest cleanup. Neptune, the failed Imfinzi-tremelimumab phase 3, also landed on the scrapheap, as did two phase 2 programs and one phase 1 study.

AstraZeneca’s Dynavax-partnered TLR9 agonist AZD1419 was one of the phase 2 programs to get the chop. A phase 2a trial of the drug in asthma missed its primary endpoint late last year. The other culled phase 2 is MEDI8852, an anti-influenza A monoclonal antibody. 

Finally, AstraZeneca gave MEDI0700 the boot. The bispecific originated at Amgen and moved into the clinic as a treatment for systemic lupus erythematosus. However, like some other drugs stemming from the AstraZeneca-Amgen deal, it has failed to make it through the clinic.