Orpathys (savolitinib)

Savolitinib monotherapy showed encouraging antitumor activities and a tolerable safety profile in heavily treated, later-line METamp G/GEJ cancers, supporting further investigation in randomized controlled trials. ClinicalTrials.gov identifier: NCT04923932 .

Following discontinuation of Savolitinib due to drug-induced liver injury, Tislelizumab, previously associated with resistance, was reintroduced as a "rechallenge" successfully re-establishing disease control. Coupled with a systematic review of pertinent literature, this article explores the clinical features, therapeutic challenges, potential resistance mechanisms, and management approaches for such patients. It also outlines future research avenues for combination or sequential therapies, aiming to furnish a more holistic reference for clinical decision-making.

P3, N=216, Completed, Hutchison Medipharma Limited | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Aug 2025 | Trial primary completion date: Dec 2025 --> Aug 2025

Drug sensitivity analysis indicated that tozasertib, savolitinib, AZD4547, IWP-2, and GSK591 may have potential therapeutic value. Multi-omics analyses revealed that these key genes are regulated by DNA methylation and transcription factor networks. The actin cytoskeleton-based gene signature serves as an independent indicator of poor prognosis and may support precise prognostic assessment and personalized therapeutic strategies for GBM.

This study provides a comprehensive characterization of METΔex14 in NSCLC, revealing its dual role as a primary driver of oncogenesis and a potential resistance mechanism to EGFR/ALK inhibitors. The identification of concurrent genetic alterations and potential resistance mechanisms enhances our molecular understanding of treatment responses. These findings highlight the need for further investigation into targeted therapies that consider the genomic complexity of METΔex14 to improve treatment efficacy and patient outcomes.

P3, N=148, Active, not recruiting, AstraZeneca | Trial completion date: Oct 2025 --> Feb 2027 | Trial primary completion date: Jun 2025 --> Dec 2025

OncoPredict suggested higher sensitivity in the high-risk group to 5-fluorouracil, PI3K-AKT-mTOR inhibitors (afuresertib, pictilisib, taselisib, dactolisib), and the MET inhibitor savolitinib. Multi-omic integration of PCD-related genes delineates PCD-driven heterogeneity in AML and yields a robust five-gene prognostic model with therapeutic implications. CORO1A emerges as a potential apoptosis-associated oncogene that promoting AML cell survival.

P2, N=110, Completed, Hutchison Medipharma Limited | Active, not recruiting --> Completed | N=75 --> 110 | Trial completion date: Dec 2026 --> Apr 2026 | Trial primary completion date: Dec 2026 --> Apr 2026

Savolitinib plus durvalumab shows OS in MET-driven PRC, supporting the ongoing SAMETA RIII trial (ClinicalTrials.gov identifier: NCT05043090). ctDNA may be a useful predictive biomarker.

The disease proved refractory to multiple lines of therapy, including platinum-based chemotherapy, immunotherapy, intrathoracic instillation and a subsequent individualized regimen comprising intraperitoneal cisplatin plus sintilimab for local disease control and potential immunomodulation synergized with oral anlotinib. It illustrates that rare but actionable genomic alterations, such as MET amplification, can be identified through liquid or tissue biopsy and can inform successful targeted treatment strategies, even in a tumor type where such alterations are uncommon. Histological classification combined with molecular profiling remains pivotal for personalized oncology.

P3, N=345, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting | Trial primary completion date: Jun 2025 --> Jun 2026

Savolitinib demonstrated robust and durable efficacy in patients with METex14-mutated, locally advanced NSCLC with manageable safety, supporting savolitinib as a treatment option in this disease setting. HUTCHMED, AstraZeneca.