Phase 3 study launches of savolitinib/durvalumab combo in papillary renal cell carcinoma

The first patient has been treated in the global phase 3 SAMETA trial evaluating the combination of the investigational MET inhibitor savolitinib and PD-L1 inhibitor durvalumab (Imfinzi) in patients with MET-driven advanced papillary renal cell carcinoma (PRCC).1

The open-label, multicenter study (NCT05043090) is randomizing patients in a 2:1:1 ratio to the MET/PD-L1 inhibitor combination, monotherapy with the tyrosine kinase inhibitor (TKI) sunitinib (Sutent), or single-agent durvalumab.2

“Savolitinib is an oral, potent, and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations) or gene amplification,” wrote HUTCHMED, the codeveloper of savolitinib, in a recent news release.1

Patients are eligible to enroll in the SAMETA trial if they have confirmed MET-driven PRCC that is both unresectable and either locally advanced or metastatic. They are unable to enroll if they were previously treated in the metastatic setting or were exposed to a MET inhibitor, durvalumab, or sunitinib in any setting.

The trial is taking place is many countries, including Argentina, Australia, Brazil, Czechia, France, Italy, the Republic of Korea, Mexico, Poland, Spain, Taiwan, Turkey, and the United Kingdom. Global enrollment for this study continues. The investigators of this study plan to assess about 200 patients.

Patients in the experimental arm will receive 600 mg of savolitinib orally once a day plus 1500 mg of durvalumab intravenously every 4 weeks. In the sunitinib control arm, treatment will comprise 50 mg of sunitinib orally once a day for 4 consecutive weeks along with a 2-week sunitinib-free interval (ie, 6-week cycles). In the immunotherapy control arm, patients will receive 1500 mg of durvalumab monotherapy intravenously every 4 weeks.

Participants will continue with treatment until radiological progression (PD; RECIST 1.1), unacceptable toxicity, or withdrawal of consent. Cross over to the combination arm is allowed for patients with radiological PD in the durvalumab control arm.

The primary end point of this study is median progression free survival (PFS). Secondary end points include overall survival (OS), objective response rate (ORR), duration of response (DOR), disease control rate at 6 and 12 months, and quality of life. The estimated primary completion date is March 8, 2024.

Savolitinib in prior kidney cancer trials

The SAMETA trial was launched after previously studies were conducted demonstrating the efficacy of savolitinib in patients with RCC. For example, results from the trial (NCT03091192) showed ORRs of 27% versus 7% with single-agent savolitinib versus sunitinib, respectively, in patients with MET-driven PRCC. The results also showed that at the data cutoff, no savolitinib responders had disease progression and the OS hazard ratio was “encouraging” at 0.51, although the data were still maturing.1

Another study, the phase 2 CALPYSO trial (NCT02819596), showed early promise for the savolitinib/durvalumab combination in kidney cancer. Among a cohort of 41 patients with PRCC showed that 8 (57%) of 14 patients with MET-driven disease achieved a confirmed response. The median DOR was 9.4 months. The efficacy data also showed a median OS of 27.4 months and a median PFS of 10.5 months.1

References

1. HUTCHMED and AstraZeneca initiate SAMETA global phase III trial of savolitinib in combination with PD-L1 inhibitor IMFINZI in patients with MET-driven advanced papillary renal cell carcinoma. Published online November 1, 2021. Accessed November 1, 2021. https://bit.ly/3CF4vr4.

2. National Institutes of Health US National Library of Medicine ClinicalTrials.gov. Savolitinib plus durvalumab versus sunitinib and durvalumab monotherapy in MET-driven, unresectable and locally advanced or metastatic PRCC (SAMETA). Updated September 13, 2021. Accessed November 1, 2021. https://clinicaltrials.gov/ct2/show/NCT05043090.