BACK

MET inhibition

CompoundSavolitinib

Area under investigation

Advanced solid tumors, EGFRm NSCLC, Gastric cancer, MET-driven NSCLC, RCC

Scientific PillarTumor Drivers & Resistance Mechanisms

Target Overview

Aberrant activation of the MET receptor tyrosine kinase pathway through mutation, protein overexpression or gene amplification has been implicated in oncogenesis and tumor cell growth.1,2

Alterations in MET signaling are associated with lung cancer, papillary renal cell carcinoma, gastric cancer, and colorectal cancer.3-6

MET overexpression and/or amplification is an acquired resistance mechanism to early generation EGFR-TKIs and osimertinib in EGFRm NSCLC.7,8

 

Compound Overview

Savolitiniba is an investigational potent and selective MET inhibitor that is being clinically evaluated as a potential treatment for NSCLC cancer and other cancers.

aSavolitinib, partnered with HUTCHMED.

Mechanism of Action

  • Mechanism of Action

Figure adapted from Eder JP, Vande Woude GF, Boerner SA, et al. Clin Cancer Res. 2009;15(7):2207-2214.

References

1. Organ SL, Tsao MS. Ther Adv Med Oncol. 2011;3(1 suppl):S7-S19. 2. Maroun CR, Rowlands T. Pharmacol Ther. 2014;142(3):316-338. 3. Olivero M, Valente G, Bardelli A, et al. Int J Cancer. 1999;82(5):640-643. 4. Schmidt L, Junker K, Nakaigawa N, et al. Oncogene. 1999;18(14):2343-2350. 5. Sierra JR, Tsao MS. Ther Adv Med Oncol. 2011;3(1 suppl):S21-S35. 6. Bardelli A, Corso S, Bertotti A, et al. Cancer Discov. 2013;3(6):658-673. 7. Piotrowska Z, Thress K, Mooradian M, et al. Poster presented at: American Society of Clinical Oncology 2017; June 2-6, 2017; Chicago, IL. Abs 9020. 8. Yu HA, Arcila ME, Rekhtman N, et al. Clin Cancer Res. 2013;19(8):2240-2247.

Target Overview

Aberrant activation of the MET receptor tyrosine kinase pathway through mutation, protein overexpression or gene amplification has been implicated in oncogenesis and tumor cell growth.1,2

Alterations in MET signaling are associated with lung cancer, papillary renal cell carcinoma, gastric cancer, and colorectal cancer.3-6

MET overexpression and/or amplification is an acquired resistance mechanism to early generation EGFR-TKIs and osimertinib in EGFRm NSCLC.7,8

 

Compound Overview

Savolitiniba is an investigational potent and selective MET inhibitor that is being clinically evaluated as a potential treatment for NSCLC cancer and other cancers.

aSavolitinib, partnered with HUTCHMED.

Mechanism of Action

  • Mechanism of Action

Figure adapted from Eder JP, Vande Woude GF, Boerner SA, et al. Clin Cancer Res. 2009;15(7):2207-2214.

References

1. Organ SL, Tsao MS. Ther Adv Med Oncol. 2011;3(1 suppl):S7-S19. 2. Maroun CR, Rowlands T. Pharmacol Ther. 2014;142(3):316-338. 3. Olivero M, Valente G, Bardelli A, et al. Int J Cancer. 1999;82(5):640-643. 4. Schmidt L, Junker K, Nakaigawa N, et al. Oncogene. 1999;18(14):2343-2350. 5. Sierra JR, Tsao MS. Ther Adv Med Oncol. 2011;3(1 suppl):S21-S35. 6. Bardelli A, Corso S, Bertotti A, et al. Cancer Discov. 2013;3(6):658-673. 7. Piotrowska Z, Thress K, Mooradian M, et al. Poster presented at: American Society of Clinical Oncology 2017; June 2-6, 2017; Chicago, IL. Abs 9020. 8. Yu HA, Arcila ME, Rekhtman N, et al. Clin Cancer Res. 2013;19(8):2240-2247.

Clinical trial information


Select trial for more information

Area under investigation=true,EGFRm NSCLC,MET-driven NSCLC

ORCHARD trial overview

Tumor

Advanced/metastatic EGFRm NSCLC with disease progression following 1L therapy with osimertinib

Trial Identifier

NCT03944772

Phase

II

Stage

Advanced/metastatic NSCLC

Regimen

Osimertinib + (savolitinib or gefitinib or necitumumab or alectinib or selpercatinib or pemetrexed + PtCh or selumetinib or Dato-DXd); durvalumab + pemetrexed + carboplatin; durvalumab + etoposide + PtCh

Visit ct.gov
Go

SAFFRON trial overview

Tumor

Locally advanced or metastatic EGFRm, MET overexpressed and/or amplified (IHC3+/≥90% and/or FISH10+) NSCLC that progressed on 1L or 2L osimertinib therapy

Trial Identifier

NCT05261399

Phase

III

Stage

Metastatic, ≥2L

Regimen

Osimertinib + savolitinib; pemetrexed + PtCh

Visit ct.gov

Savolitinib, partnered with HUTCHMED

Go

SAVANNAH trial overview

Tumor

EGFRm and MET overexpressed and/or amplified (IHC3+/≥90% and/or FISH10+), locally advanced or metastatic NSCLC that progressed following 1L osimertinib treatment

Trial Identifier

NCT03778229

Phase

II

Stage

Metastatic, ≥2L

Regimen

Osimertinib + savolitinib; placebo + savolitinib

Visit ct.gov

Savolitinib, partnered with HUTCHMED

Go

Abbreviations

View full glossary

  • 1L

    first line

  • 2L

    second line

  • 4EBP1

    eukaryotic translation initiation factor 4E binding protein 1

  • AKT

    protein kinase B/also known as PKB

  • DCR

    disease control rate

  • DoR

    duration of response

  • EGFR

    epidermal growth factor receptor

  • EGFRm

    epidermal growth factor receptor mutation

  • ERK

    extracellular signal-regulated kinase

  • FAK

    focal adhesion kinase

  • FH

    fumarate hydratase

  • FISH10+

    fluorescence in situ hybridization (MET copy ≥10)

  • GAB1

    GRB2-associated binding protein 1 of 40 kDa

  • GRB2

    growth factor receptor-bound protein 2

  • HGF

    hepatocyte growth factor

  • IHC3+/≥90%

    3+ immunohistochemistry overexpression in 90% of tumor cells

  • IV

    intravenous

  • MEK

    mitogen-activated protein kinase

  • MET

    hepatocyte growth factor receptor

  • mTORC

    mammalian target of rapamycin complex

  • NEC

    large cell neuroendocrine carcinoma

  • NSCLC

    non-small cell lung cancer

  • ORR

    overall or objective response rate

  • OS

    overall survival

  • PAK

    p21 activated kinase

  • PD

    progressive disease

  • PFS

    progression-free survival

  • PFS2

    time to second progression or death

  • PI3K

    phosphoinositide 3-kinase

  • pRCC

    papillary renal cell carcinoma

  • PtCh

    platinum-based chemotherapy

  • Q4W

    every 4 weeks

  • R

    randomization

  • RAC

    Ras-related c3 botulinum toxin substrate

  • RAF

    rapidly accelerated fibrosarcoma

  • RAS

    GTPase protein family that includes KRAS, HRAS, and NRAS

  • RECIST

    Response Evaluation Criteria in Solid Tumors

  • S6K

    S6 kinase

  • SoC

    standard of care

  • SOS

    son of sevenless

  • TKI

    tyrosine kinase inhibitor

  • tSCLC

    transformed small cell lung cancer

Some compounds herein refer to selected AstraZeneca pipeline products still under development. AstraZeneca pipeline products are investigational products and, as such, are not approved by the US Food & Drug Administration (FDA), the European Medicines Agency (EMA) or any other regulatory agency for the uses under investigation. Information regarding these investigational products should, under no circumstances, be regarded as a recommendation for their use or of their safety or efficacy.

This site is intended for US Healthcare Professionals.

Veeva ID: Z4-84958 US-109129 DE-92568 Last Updated October 20263/26
©2026 AstraZeneca. All rights reserved.