AstraZeneca Discontinues Phase 3 Monotherapy Trial of Savolitinib in Papillary Renal Cell Carcinoma

Compiled by Keke

AstraZeneca Discontinues Late-Stage Clinical Trial of Savolitinib (Volitinib) as a Monotherapy for Papillary Renal Cell Carcinoma (PRCC) in Collaboration with HUTCHMED. This Phase 3 clinical study is one of five projects being discontinued as part of AstraZeneca’s strategy to streamline its R&D pipeline, initiated in the second quarter of this year.

According to a report by FierceBiotech, on October 24, AstraZeneca confirmed that the clinical trial of savolitinib as a monotherapy for PRCC had reached its endpoint. Although the drug has been removed from the company’s Phase III clinical development pipeline, AstraZeneca and HUTCHMED will continue to study it, both as a monotherapy and in combination with other drugs.

According to HUTCHMED’s official website, as of September 30, the CALYPSO study evaluating savolitinib in combination with AstraZeneca’s PD-L1 immunotherapy Imfinzi for patients with all types of papillary renal cell carcinoma (PRCC) is still ongoing. In addition to monotherapy studies, HUTCHMED is also conducting multiple Phase Ib and II clinical trials of savolitinib, both as a single agent and in combination regimens, for the treatment of renal cell carcinoma, lung cancer, and gastric cancer.

HUTCHMED's Pipeline in Development

Savolitinib is a selective inhibitor of the mesenchymal-epithelial transition factor (MET) receptor tyrosine kinase, an enzyme that has been demonstrated to exhibit aberrant activity in various types of solid tumors. The drug was designed through chemical structure modifications specifically to address renal toxicity, which remains a major concern with several other existing selective MET inhibitors. To date, clinical trials involving more than 900 patients worldwide have shown that savolitinib has an acceptable safety profile and has demonstrated promising signs of clinical efficacy in patients with lung, kidney, gastric, and prostate cancers harboring MET gene alterations.

In 2017, AstraZeneca and HUTCHMED collaborated to initiate the SAVOIR Phase 3 clinical trial, comparing savolitinib with Pfizer’s Sutent for the treatment of papillary renal cell carcinoma (PRCC). This study was the first pivotal clinical trial conducted in patients with c-MET–expressing PRCC and was initially completed in August this year. However, data from a previous analysis suggest that the likelihood of the SAVOIR trial ultimately meeting its positive expectations is very slim.

In late 2018, HUTCHMED stated that savolitinib was unlikely to outperform Sutent in a first-line treatment trial for patients with MET-positive papillary renal cell carcinoma (PRCC). AstraZeneca and HUTCHMED subsequently halted enrollment in the trial after 60 patients had been enrolled, resulting in a sample size far below the initially planned 180 participants. This change reflected the diminished likelihood of success for savolitinib as a first-line therapy, given that restricting Sutent to second-line treatment alone is not clinically practical.

Savolitinib monotherapy study has become one of the projects in AstraZeneca's latest clinical pipeline cleanup, and the failed Phase 3 Neptune trial of Imfinzi combined with tremelimumab as first-line treatment for non-small cell lung cancer has also been removed from the current pipeline.

AstraZeneca’s TLR9 agonist AZD1419, developed in partnership with Dynavax, was one of two Phase II clinical studies discontinued after the drug failed to meet its primary endpoint in a Phase IIa asthma trial at the end of 2018; the other discontinued program was the anti-influenza A monoclonal antibody MEDI8852. The bispecific antibody MEDI0700, originally from Amgen, for the treatment of systemic lupus erythematosus, was the only Phase I clinical project divested.

AstraZeneca Updates Changes to Research Projects Starting in Q2 This Year

This change in collaboration is only part of AstraZeneca’s R&D adjustments. According to the company’s third-quarter financial report released on October 24, its overall performance remained robust. The report showed that AstraZeneca’s total sales in the third quarter reached $6.132 billion, a year-on-year increase of 16%. The new anti-cancer drugs Tagrisso, Lynparza, and Imfinzi, together with the Chinese market, once again drove growth.

Notably, sales of Tagrisso, the EGFR-targeted lung cancer drug, increased by 13.6% year-over-year to reach $891 million, exceeding expectations by 4% and making it AstraZeneca’s best-selling drug. The immuno-oncology therapy Imfinzi generated third-quarter sales of $412 million. Revenue from the PARP inhibitor Lynparza amounted to $327 million in the third quarter, surpassing expectations by 8%. Furthermore, despite expectations that China’s economic growth would slow in the second half of the year, turnover in the Chinese market still achieved a robust 40% growth in the third quarter.

Reference source: AstraZeneca dumps phase 3 renal cell carcinoma program