Orpathys (savolitinib)

Savolitinib plus osimertinib demonstrated numerically higher clinical activity versus savolitinib plus placebo in all patients and patients with higher MET biomarker cutoffs.

LR group had lower TIDE scores and lower IC50 values (Alpelisib, Ibrutinib, Sapitinib, and Savolitinib). Patients in LR group had potential advantages in survival, immune response, and drug sensitivity. In summary, the results offered new insights into prognosis prediction, immunotherapy, and personalized treatment of LUSC.

Splice site mutations around or within exon 14 of MET (METex14+) are rare, but are one of the common actionable driver mutations in elderly patients with non-small cell lung cancer (NSCLC). On June 30, 2025, vebreltinib has been approved for NSCLC with MET amplification while combination of savoltinib and osimertinib has been approved for EGFR+ post EGFR TKINSCLC with MET amplification post EGFR TKI based on the SACHI trial (NCT05015608). We discuss the current unmet clinical need (need to develop Type II MET TKI to overcome acquired resistance MET mutations at D1228 and Y1230) and future optimal treatment approaches.

Osimertinib plus savolitinib demonstrated encouraging clinical benefit in patients with EGFR-mutated advanced NSCLC and MET amplification following PD on first-line osimertinib. Safety was consistent with profiles of the individual drugs.

The combined treatment of savolitinib and gefitinib effectively controlled the disease, resulting in a favorable long-term clinical outcome. ctDNA monitoring enabled precise dose modulation that balanced therapeutic efficacy with toxicity management. This case establishes a paradigm for chronic cancer management, demonstrating that integrating molecular diagnostics with dynamic treatment optimization can effectively convert aggressive malignancies into manageable chronic conditions while preserving the quality of life of patients.

Second, it examines clinical progress in targeting classical oncogenic drivers, exemplified by the fourth-generation tyrosine kinase inhibitor amivantamab against epidermal growth factor receptor (EGFR), and explores mechanisms of drug resistance, such as T790M and C797S mutations, along with emerging strategies like synthetic lethality-based interventions. Third, it discusses combination regimens-such as osimertinib co-administered with savolitinib-that mitigate resistance by synergistically inhibiting compensatory signaling pathways, thereby enhancing clinical outcomes. Future research priorities include the design of multi-target therapeutics and the refinement of AI-driven target discovery frameworks. This review addresses current limitations in targeted NSCLC therapy and offers insights to guide future therapeutic development.

P3, N=320, Active, not recruiting, Hutchison Medipharma Limited | Recruiting --> Active, not recruiting | Trial completion date: Jan 2025 --> Aug 2026 | Trial primary completion date: Nov 2024 --> Aug 2026

The receptor tyrosine kinase mesenchymal-epithelial transition factor inhibitor savolitinib is currently being evaluated as a treatment in non-small cell lung cancer (NSCLC) in combination with osimertinib. This study demonstrates blood-brain barrier penetrance and exposure of the mesenchymal-epithelial transition inhibitor savolitinib in the nonhuman primate brain. If a similar penetrance in humans is observed, it may help to prevent and/or treat brain metastasis in non-small cell lung cancer patients.

P2, N=200, Active, not recruiting, Canadian Cancer Trials Group | Trial primary completion date: Jun 2025 --> Oct 2024

Finally, we found that hyper-immunogenicity may be sensitive to immunotherapy and certain drugs (AZD5991, Ibrutinib, Osimertinib, AGI-5198, Savolitinib, Sapitinib, AZ960, AZD3759 and Ruxolitinib), while PCI-34051 and Vorinostat showed sensitivity in patients with hypo-immunogenicity. Our results demonstrate that ICD plays an important role in UCEC progression, suggesting that ICD-related markers could serve as potential targets for prognosis and treatment.

In summary, both CID_134565115 and CID_153611202 demonstrated favorable binding energies and distinctive interaction patterns, surpassing the established Savolitinib. Although our computational study highlights the promising potential of these lead-like candidates in obstructing oncogenic c-MET signaling, further experimental investigations are necessary to verify and establish their preclinical relevance.

To date, the MET tyrosine-kinase inhibitors (TKIs) capmatinib, tepotinib and savolitinib have been approved for the treatment of advanced-stage METex14-mutant NSCLC...Indeed, in May 2025, the MET-directed ADC telisotuzumab vedotin was approved by the FDA for patients with previously treated advanced-stage nonsquamous NSCLC overexpressing MET (≥50% of tumour cells with 3+ staining on immunohistochemistry). Understanding the unique MET-related adverse events will be crucial when incorporating these agents into daily clinical practice. In this Review, we highlight the rationale for targeting MET alterations across various solid tumour types and provide a summary of the clinical efficacy and toxicity profiles of the approved and emerging MET-targeted TKIs, monoclonal or bispecific antibodies and ADCs.