SAVANNAH Trial Evaluates Adding Savolitinib to Osimertinib After Progression of NSCLC

By Cecilia Brown - Last Updated: March 27, 2025

Savolitinib plus osimertinib “demonstrated clinically meaningful and durable” responses in patients with EGFR-mutated advanced non–small cell lung cancer (NSCLC) and MET overexpression who had disease progression during first-line treatment with osimertinib, according to results from the SAVANNAH trial.

Myung-Ju Ahn, MD, PhD, of the Sungkyunkwan University School of Medicine, presented primary results from the trial during the European Lung Cancer Congress 2025 in Paris, France. The trial evaluated the combination of savolitinib, which is an oral, potent, and highly selective MET tyrosine kinase inhibitor, and osimertinib, an oral, third-generation EGFR tyrosine kinase inhibitor. The combination was studied because it “may overcome acquired MET-driven resistance” in patients with EGFR-mutated advanced NSCLC who experienced progression during treatment with osimertinib.

The study included patients with EGFR-mutated advanced NSCLC and MET overexpression and/or amplification after progressive disease during treatment with osimertinib. MET thresholds were initially defined as MET immunohistochemistry results showing 3-plus intensity in at least 50% of tumor cells or fluorescence in situ hybridization (FISH) results showing at least 5 MET gene copies or a MET-to-centromere of chromosome 7 ratio of at least 2. These thresholds were then refined to MET immunohistochemistry results showing 3-plus intensity in at least 90% of tumor cells or FISH results showing at least 10 MET gene copies.

Patients in the study (n=101) received savolitinib 300 mg twice daily plus osimertinib 80 mg once daily. The primary efficacy population (n=80) was defined as patients with progressive disease during first-line treatment with osimertinib who had either immunohistochemistry results showing 3-plus intensity in at least 90% of tumor cells or FISH results showing at least 10 MET gene copies. Among the primary efficacy population, the median age was 66 years; 70% were female and 71% were White. Most patients (60%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 1, and 39% had brain metastases at study entry.

The primary end point of the SAVANNAH study was the investigator-assessed objective response rate (ORR), with secondary end points including ORR by blinded independent central review (BICR) and duration of response and progression-free survival (PFS) by investigators and BICR. Safety was also evaluated and was reported for all patients who received savolitinib 300 mg twice daily plus osimertinib.

The investigator-assessed ORR was 56% (95% CI, 45%-67%), with a median PFS of 7.4 months (95% CI, 5.5-7.6). The median duration of response was 7.1 months (95% CI, 5.6-9.6).

Grade 3 or higher adverse events (AEs) occurred in 57% of patients, with grade 3 or higher treatment-related AEs occurring in 32% and serious AEs occurring in 31%. Adverse events leading to discontinuation of savolitinib occurred in 16%, and AEs leading to discontinuation of osimertinib occurred in 12%.

The most common all-grade AEs, occurring in at least 20% of patients, were:

Peripheral edema, 58%
Nausea, 45%
Diarrhea, 33%
Vomiting, 21%

The study investigators noted that “no new safety concerns emerged” with the combination regimen. Based on these results, Dr. Ahn and colleagues concluded that the “combination offers a potential treatment option in this setting,” noting that savolitinib plus osimertinib is under further investigation in the ongoing phase 3 SAFFRON study.

Reference

Ahn MJ, Bonanno L, Cheng S, et al. SAVANNAH: Savolitinib (savo) + osimertinib (osi) in patients (pts) with EGFRm advanced NSCLC and MET overexpression (OverExp) and/or amplification (Amp) following progressive disease (PD) on osi. Abstract #2O. Presented at European Lung Cancer Congress 2025, March 26-29; Paris, France.

In the photo at top, Myung-Ju Ahn, MD, PhD, of the Sungkyunkwan University School of Medicine, presents primary results from the SAVANNAH trial during the European Lung Cancer Congress 2025 in Paris, France. (Photo courtesy of the European Society for Medical Oncology)