Therapy Detail

Therapy Name Savolitinib
Synonyms
Therapy Description

Savolitinib (AZD6094) is a selective MET inhibitor, which inhibits MET kinase activity, resulting in decreased downstream signaling, and may inhibit growth of MET-expressing tumors (PMID: 25248999).

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Drug Name Trade Name Synonyms Drug Classes Drug Description
Savolitinib HMPL-504|AZD6094|Volitinib MET Inhibitor 51 Savolitinib (AZD6094) is a selective MET inhibitor, which inhibits MET kinase activity, resulting in decreased downstream signaling, and may inhibit growth of MET-expressing tumors (PMID: 25248999).

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
MET act mut papillary renal cell carcinoma predicted - sensitive Savolitinib Phase II Actionable In a Phase II trial, treatment with Savolitinib (AZD6094) resulted in an overall response rate (ORR) of 18% (8/44, all partial responses) in the subgroup of patients with MET-driven papillary renal cell carcinoma (PRCC), which included patients with MET kinase domain mutations, compared to an ORR of 0% (0/46) in patients with MET-independent PRCC (PMID: 28644771; NCT02127710). 28644771
MET amp papillary renal cell carcinoma sensitive Savolitinib Phase II Actionable In a Phase II trial, treatment with Savolitinib (AZD6094) resulted in an overall response rate (ORR) of 18% (8/44, all partial responses) in the subgroup of patients with MET-driven papillary renal cell carcinoma (PRCC), which included patients with MET amplification, compared to an ORR of 0% (0/46) in patients with MET-independent PRCC (PMID: 28644771; NCT02127710). 28644771
MET amp papillary renal cell carcinoma sensitive Savolitinib Preclinical - Pdx Actionable In a preclinical study, Savolitinib (AZD6094) demonstrated antitumor activity in patient-derived papillary renal cell carcinoma xenograft models harboring MET amplification (PMID: 25779944). 25779944
MET amp papillary renal cell carcinoma sensitive Savolitinib Case Reports/Case Series Actionable In a Phase I trial, treatment with Savolitinib (AZD6094) was well-tolerated and resulted in partial response in 8% (3/39) of patients with advanced solid tumors, with all 3 responses in patients with papillary renal cell carcinoma, 1 with MET amplification and 2 with chromosome 7 gain (PMID: 30952639; NCT01773018). 30952639
MET D1228N Advanced Solid Tumor predicted - resistant Savolitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing mouse MET D1226N (corresponds to MET D1228N in humans) were resistant to treatment with Savolitinib (AZD6094), demonstrating sustained cell growth in culture (PMID: 28396313). 28396313
MET Y1230H Advanced Solid Tumor predicted - resistant Savolitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing mouse MET Y1228H (corresponds to MET Y1230H in humans) were resistant to treatment with Savolitinib (AZD6094), demonstrating sustained cell growth in culture (PMID: 28396313). 28396313
MET del exon14 lung non-small cell carcinoma predicted - sensitive Savolitinib Phase II Actionable In a Phase II trial, Savolitinib (AZD6094) treatmetn resulted in partial response in 51.6% (16/31) and stable disease in 32.3% (10/31) of patients with pulmonary sarcomatoid carcinoma (n=14) or other types of non-small cell lung cancer (n=20) harboring MET exon 14 skipping mutations (AACR Annual Meeting 2019, Abstract CT301; NCT02897479). detail...
MET D1228V Advanced Solid Tumor resistant Savolitinib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells expressing MET D1228V demonstrated resistance to treatment with Savolitinib (AZD6094) in culture, resulting in sustained Met phosphorylation (PMID: 27694386). 27694386

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Clinical Trial Phase Therapies Title Recruitment Status
NCT03592641 Phase II Savolitinib Volitinib in Treating Participants With MET Amplified Metastatic or Unresectable Colorectal Cancer Recruiting
NCT03598244 Phase I Savolitinib Volitinib in Treating Participants With Recurrent or Refractory Primary CNS Tumors Recruiting
NCT02761057 Phase II Savolitinib Cabozantinib Crizotinib Sunitinib Cabozantinib-S-Malate, Crizotinib, Volitinib, or Sunitinib Malate in Treating Patients With Locally Advanced or Metastatic Kidney Cancer Recruiting
NCT03385655 Phase II Savolitinib Darolutamide Adavosertib Prostate Cancer Biomarker Enrichment and Treatment Selection Recruiting
NCT02143466 Phase I Osimertinib + Savolitinib Savolitinib Osimertinib + Selumetinib Durvalumab + Osimertinib AZD9291 in Combination With Ascending Doses of Novel Therapeutics Active, not recruiting
NCT03091192 Phase III Sunitinib Savolitinib Savolitinib vs. Sunitinib in MET-driven PRCC Active, not recruiting
NCT02127710 Phase II Savolitinib A Phase II Trial to Evaluate the Efficacy of AZD6094 (HMPL-504) in Patients With Papillary Renal Cell Carcinoma (PRCC) Active, not recruiting


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