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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
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.
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Abbreviations
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
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
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
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Selected Filter(s)
Abbreviations
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