^
2ms
Screening of differential gene expression patterns through survival analysis for diagnosis, prognosis and therapies of clear cell renal cell carcinoma. (PubMed, PLoS One)
Then we detected 10 repurposable drug molecules (Irinotecan, Imatinib, Telaglenastat, Olaparib, RG-4733, Sorafenib, Sitravatinib, Cabozantinib, Abemaciclib, and Dovitinib.) by molecular docking with KGs-mediated receptor proteins. Their ADME/T analysis and cross-validation with the independent receptors, also supported their potent against ccRCC. Therefore, these outputs might be useful inputs/resources to the wet-lab researchers and clinicians for considering an effective treatment strategy against ccRCC.
Journal • PARP Biomarker
|
CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • SERPINA5 (Serpin Family A Member 5)
|
Lynparza (olaparib) • sorafenib • imatinib • Verzenio (abemaciclib) • Cabometyx (cabozantinib tablet) • irinotecan • dovitinib (TKI258) • telaglenastat (CB-839) • sitravatinib (MGCD516) • RG4733
2ms
SAFFRON-104: a phase Ib/II study of sitravatinib alone or with tislelizumab in advanced hepatocellular carcinoma and gastric cancer/gastroesophageal junction cancer. (PubMed, Cancer Immunol Immunother)
Sitravatinib with/without tislelizumab was generally well tolerated and showed preliminary antitumor activity in patients with advanced HCC and GC/GEJC.
P1/2 data • Journal • Metastases
|
AXL (AXL Receptor Tyrosine Kinase) • KDR (Kinase insert domain receptor)
|
Tevimbra (tislelizumab-jsgr) • sitravatinib (MGCD516)
3ms
Targeting multiple receptor tyrosine kinases with sitravatinib: A Phase 1b study in advanced renal cell carcinoma and castrate-resistant prostate cancer. (PubMed, Invest New Drugs)
Strong indicators for clinical activity were not seen in patients with CRPC and bone metastases. Clinical trial registration:ClinicalTrials.gov NCT02219711.
P1 data • Journal • Metastases
|
AXL (AXL Receptor Tyrosine Kinase) • KDR (Kinase insert domain receptor)
|
sitravatinib (MGCD516)
4ms
AAAQ8661: Sitravatinib in Advanced Liposarcoma and Other Soft Tissue Sarcomas (clinicaltrials.gov)
P2, N=29, Completed, Columbia University | Active, not recruiting --> Completed
Trial completion • Metastases
|
sitravatinib (MGCD516)
5ms
Targeting Tyro3, Axl, and MerTK Receptor Tyrosine Kinases Significantly Sensitizes Triple-Negative Breast Cancer to CDK4/6 Inhibition. (PubMed, Cancers (Basel))
Given the roles of the TAM receptors in promoting the creation of an immunosuppressive tumor microenvironment (TME), we further demonstrate that the combination of CDK4/6 inhibitor abemaciclib and sitravatinib modifies the immune landscape of TNBC to favor immune checkpoint blockade. Overall, our study offers a novel and highly effective combination therapy against TNBC and potentially treatment-resistant HER2+ breast cancer that can be rapidly moved to the clinic.
Journal
|
RB1 (RB Transcriptional Corepressor 1) • AXL (AXL Receptor Tyrosine Kinase) • MERTK (MER Proto-Oncogene, Tyrosine Kinase)
|
Verzenio (abemaciclib) • sitravatinib (MGCD516)
5ms
SAPPHIRE: Phase 3 Study of Sitravatinib Plus Nivolumab vs Docetaxel in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer (clinicaltrials.gov)
P3, N=577, Active, not recruiting, Mirati Therapeutics Inc. | Trial completion date: Apr 2024 --> Dec 2024
Trial completion date • Combination therapy • Checkpoint inhibition • Metastases
|
PD-L1 (Programmed death ligand 1)
|
Opdivo (nivolumab) • docetaxel • sitravatinib (MGCD516)
5ms
Phase classification • Combination therapy • Metastases
|
Tevimbra (tislelizumab-jsgr) • sitravatinib (MGCD516)
5ms
Study of Sitravatinib, Nivolumab and Ipilimumab in Advanced or Metastatic Clear-Cell Renal Cell Carcinoma or Other Solid Malignancies (clinicaltrials.gov)
P1, N=22, Completed, Mirati Therapeutics Inc. | Active, not recruiting --> Completed | N=92 --> 22 | Trial completion date: Feb 2024 --> Jun 2023
Trial completion • Enrollment change • Trial completion date • Combination therapy • Metastases
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • sitravatinib (MGCD516)
6ms
H-43432: Sitravatinib in Metastatic Breast Cancer (clinicaltrials.gov)
P2, N=3, Terminated, Xiang Zhang | Withdrawn --> Terminated; Terminated by sponsor due to lack of interest
Trial termination • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • PGR (Progesterone receptor) • PTPN12 (Protein Tyrosine Phosphatase Non-Receptor Type 12)
|
sitravatinib (MGCD516)
6ms
BGB-A317-290-LTE1: Study of Tislelizumab, Pamiparib, and Other Investigational Agents in Participants With Advanced Malignancies (clinicaltrials.gov)
P3, N=300, Enrolling by invitation, BeiGene | Trial completion date: Aug 2024 --> Dec 2026 | Trial primary completion date: Aug 2024 --> Dec 2026
Trial completion date • Trial primary completion date • Metastases
|
temozolomide • Lenvima (lenvatinib) • Tevimbra (tislelizumab-jsgr) • Fruzaqla (fruquintinib) • Partruvix (pamiparib) • zanidatamab (ZW25) • Avzivi (bevacizumab-tnjn) • ociperlimab (BGB-A1217) • sitravatinib (MGCD516) • BGB-15025 • BGB-A445 • LBL-007 • surzebiclimab (BGB-A425)
6ms
National Lung Matrix Trial: Multi-drug Phase II Trial in Non-Small Cell Lung Cancer (clinicaltrials.gov)
P2, N=423, Active, not recruiting, University of Birmingham | Trial completion date: Sep 2023 --> Sep 2024 | Trial primary completion date: Sep 2023 --> Sep 2024
Trial completion date • Trial primary completion date • IO biomarker
|
NKX2-1 (NK2 Homeobox 1) • TP63 (Tumor protein 63)
|
Xalkori (crizotinib) • Tagrisso (osimertinib) • Ibrance (palbociclib) • Imfinzi (durvalumab) • docetaxel • Koselugo (selumetinib) • Truqap (capivasertib) • fexagratinib (ABSK091) • ceralasertib (AZD6738) • sitravatinib (MGCD516) • vistusertib (AZD2014)
6ms
Study of Sitravatinib With or Without Other Anticancer Therapies Receiving Clinical Benefit From Parent Study (clinicaltrials.gov)
P2/3, N=55, Active, not recruiting, Mirati Therapeutics Inc. | Enrolling by invitation --> Active, not recruiting | N=200 --> 55 | Trial completion date: Apr 2024 --> Apr 2025 | Trial primary completion date: Apr 2024 --> Apr 2025
Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
Keytruda (pembrolizumab) • Opdivo (nivolumab) • Yervoy (ipilimumab) • Padcev (enfortumab vedotin-ejfv) • sitravatinib (MGCD516)
7ms
Blockade of Discoidin Domain Receptor Signaling with Sitravatinib Reveals DDR2 as a Mediator of Neuroblastoma Pathogenesis and Metastasis. (PubMed, Mol Cancer Ther)
Analysis of single cell sequencing data demonstrated that DDR2 is restricted to mesenchymal-type tumor subpopulations and is enriched in Schwann Cell Precursor (SCP) subpopulations found in high-risk disease. These data define an unsuspected role for sitravatinib as a therapeutic agent in neuroblastoma and reveal a novel function for DDR2 as a driver of tumor growth and metastasis.
Journal
|
ALK (Anaplastic lymphoma kinase) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • DDR2 (Discoidin domain receptor 2)
|
sitravatinib (MGCD516)
7ms
MRTX-500: Phase 2 Study of Glesatinib, Sitravatinib or Mocetinostat in Combination With Nivolumab in Non-Small Cell Lung Cancer (clinicaltrials.gov)
P2, N=161, Terminated, Mirati Therapeutics Inc. | Completed --> Terminated; This study was terminated as a result of Sponsor portfolio reprioritization.
Trial termination • Combination therapy • Metastases
|
Opdivo (nivolumab) • sitravatinib (MGCD516) • glesatinib (MGCD265) • mocetinostat (MGCD0103)
7ms
BTC-BGB: Phase II Study of Sitravatinib in Combination With Tislelizumab in Patients With Advanced Biliary Tract Cancer (clinicaltrials.gov)
P2, N=43, Active, not recruiting, Seoul National University Hospital | Trial completion date: Jun 2024 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Jul 2023
Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
Tevimbra (tislelizumab-jsgr) • sitravatinib (MGCD516)
8ms
H-43432: Sitravatinib in Metastatic Breast Cancer (clinicaltrials.gov)
P2, N=0, Withdrawn, C. Kent Osborne, MD | Terminated --> Withdrawn
Trial withdrawal • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • PGR (Progesterone receptor) • PTPN12 (Protein Tyrosine Phosphatase Non-Receptor Type 12)
|
sitravatinib (MGCD516)
8ms
SITISVEAL: Sitravatinib and Tislelizumab in Patients With Metastatic Uveal Melanoma With Liver Metastases. (clinicaltrials.gov)
P2, N=16, Active, not recruiting, Grupo Español Multidisciplinar de Melanoma | Recruiting --> Active, not recruiting | N=34 --> 16 | Trial completion date: Aug 2024 --> May 2024
Enrollment closed • Enrollment change • Trial completion date • Combination therapy • Metastases
|
Tevimbra (tislelizumab-jsgr) • sitravatinib (MGCD516)
9ms
Trial completion date • Trial termination • Trial primary completion date • Combination therapy • Metastases
|
docetaxel • Tevimbra (tislelizumab-jsgr) • irinotecan • sitravatinib (MGCD516)
9ms
BGB-A317-Sitra-301: Tislelizumab in Combination With Sitravatinib in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov)
P3, N=377, Terminated, BeiGene | Completed --> Terminated; Due to safety risks and unfavorable risk-benefit assessment results, the sponsor has decided to voluntarily terminate the study.
Trial termination • Combination therapy • Metastases
|
ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
PD-L1 expression • ALK rearrangement
|
docetaxel • Tevimbra (tislelizumab-jsgr) • sitravatinib (MGCD516)
9ms
Disruption of MerTK increases the efficacy of checkpoint inhibitor by enhancing ferroptosis and immune response in hepatocellular carcinoma. (PubMed, Cell Rep Med)
Sitravatinib, an inhibitor of MerTK, sensitizes resistant HCC to anti-PD-L1 therapy by promoting tumor ferroptosis and decreasing MDSC infiltration into the TME. In conclusion, we find that MerTK could serve as a predictive biomarker for patient stratification and as a promising target to overcome anti-PD-1/PD-L1 resistance in HCC.
Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
|
MERTK (MER Proto-Oncogene, Tyrosine Kinase) • SLC7A11 (Solute Carrier Family 7 Member 11)
|
MERTK expression
|
sitravatinib (MGCD516)
9ms
Sitravatinib Plus Pembrolizumab in Patients With Advanced Treatment-Naïve PD-L1+ Non-Squamous NSCLC (clinicaltrials.gov)
P2, N=9, Terminated, Sarah Goldberg | Trial completion date: Feb 2025 --> Oct 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Feb 2025 --> Jun 2023; Sponsor decision based on data from other clinical trials
Trial completion date • Trial termination • Trial primary completion date • Metastases
|
PD-L1 (Programmed death ligand 1)
|
Keytruda (pembrolizumab) • sitravatinib (MGCD516)
10ms
STELLAR: Tislelizumab Combined With Sitravatinib as Consolidation Treatment Following Concurrent Chemoradiation in Patients With Locally Advanced, Unresectable NSCLC (clinicaltrials.gov)
P2, N=5, Terminated, Fudan University | N=36 --> 5 | Recruiting --> Terminated; The trial was terminated per sponsor recommendation
Enrollment change • Trial termination • Metastases
|
Tevimbra (tislelizumab-jsgr) • sitravatinib (MGCD516)
10ms
BGB-A317-Sitra-301: Tislelizumab in Combination With Sitravatinib in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov)
P3, N=377, Completed, BeiGene | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Dec 2023 | Trial primary completion date: Jun 2024 --> Dec 2023
Trial completion • Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
PD-L1 expression • ALK rearrangement
|
docetaxel • Tevimbra (tislelizumab-jsgr) • sitravatinib (MGCD516)
11ms
A Phase 2 Study of Sitravatinib in Combination with Nivolumab in Patients with Advanced or Metastatic Urothelial Carcinoma. (PubMed, Eur Urol Oncol)
Sitravatinib plus nivolumab demonstrated a manageable safety profile but did not result in clinically meaningful ORRs in patients with advanced/metastatic UC in the eight cohorts studied.
P2 data • Journal • Combination therapy • Metastases
|
AXL (AXL Receptor Tyrosine Kinase) • KDR (Kinase insert domain receptor) • MERTK (MER Proto-Oncogene, Tyrosine Kinase)
|
Opdivo (nivolumab) • sitravatinib (MGCD516)
12ms
Sitravatinib combined with PD1 blockade enhances cytotoxic T-Cell infiltration by M2 to M1 tumor macrophage repolarization in esophageal adenocarcinoma. (PubMed, Carcinogenesis)
Additionally, pre-treatment gene expression of TAM receptors and PD-L1 were significantly higher in major responders compared to the non-responders, in animals that received sitravatinib and AUNP-12 (P < 0.02), confirming that TAM suppression enhances the efficacy of PD-1 blockade. In conclusion, this study proposes a promising immunomodulatory strategy using a multi-gene TKI to overcome developed resistance to an ICI in EAC, establishing rationale for future clinical development.
Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • CD8 (cluster of differentiation 8) • CASP3 (Caspase 3)
|
sitravatinib (MGCD516) • AUNP-12
12ms
BTC-BGB: Phase II Study of Sitravatinib in Combination With Tislelizumab in Patients With Advanced Biliary Tract Cancer (clinicaltrials.gov)
P2, N=43, Active, not recruiting, Seoul National University Hospital | Trial completion date: Dec 2023 --> Jun 2024 | Trial primary completion date: Jun 2023 --> Dec 2023
Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
Tevimbra (tislelizumab-jsgr) • sitravatinib (MGCD516)
12ms
BGB-900-2001-IIT: A Phase II Study to Explore the Safety, Tolerability, and Preliminary Antitumor Activity of Sitravatinib Plus Tislelizumab or Combination With Nab-paclitaxel in Patients With Locally Recurrent or Metastatic Triple Negative Breast Cancer (TNBC) (clinicaltrials.gov)
P2, N=98, Active, not recruiting, Fudan University | Completed --> Active, not recruiting | Trial completion date: Jun 2023 --> Jun 2024 | Trial primary completion date: Jun 2023 --> Jun 2024
Enrollment closed • Trial completion date • Trial primary completion date • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
|
ER negative • PGR negative
|
Tevimbra (tislelizumab-jsgr) • albumin-bound paclitaxel • sitravatinib (MGCD516)
1year
Trial completion • Trial primary completion date • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
|
ER negative • PGR negative
|
Tevimbra (tislelizumab-jsgr) • albumin-bound paclitaxel • sitravatinib (MGCD516)
1year
Enrollment open • Combination therapy
|
docetaxel • Tevimbra (tislelizumab-jsgr) • Cyramza (ramucirumab) • sitravatinib (MGCD516) • BGB-15025 • BGB-A445
1year
Enrollment open • Combination therapy • Metastases
|
docetaxel • Tevimbra (tislelizumab-jsgr) • irinotecan • sitravatinib (MGCD516)
1year
SAPPHIRE: Phase 3 Study of Sitravatinib Plus Nivolumab vs Docetaxel in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer (clinicaltrials.gov)
P3, N=532, Active, not recruiting, Mirati Therapeutics Inc. | Trial completion date: Jul 2023 --> Apr 2024 | Trial primary completion date: Sep 2022 --> Mar 2023
Trial completion date • Trial primary completion date • Combination therapy • Checkpoint inhibition • Metastases
|
PD-L1 (Programmed death ligand 1)
|
Opdivo (nivolumab) • docetaxel • sitravatinib (MGCD516)
1year
Study of Sitravatinib, Nivolumab and Ipilimumab in Advanced or Metastatic Clear-Cell Renal Cell Carcinoma or Other Solid Malignancies (clinicaltrials.gov)
P1, N=92, Active, not recruiting, Mirati Therapeutics Inc. | Trial completion date: Jun 2023 --> Feb 2024 | Trial primary completion date: Mar 2023 --> Jun 2023
Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • sitravatinib (MGCD516)
1year
Trial completion
|
sitravatinib (MGCD516)
1year
PK Study to Assess Drug-drug Interaction and QTc Between Sitravatinib and a Cocktail of Substrates (clinicaltrials.gov)
P1, N=40, Completed, Mirati Therapeutics Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Dec 2022 | Trial primary completion date: Jun 2023 --> Dec 2022
Trial completion • Trial completion date • Trial primary completion date • Metastases
|
Opdivo (nivolumab) • sitravatinib (MGCD516) • midazolam hydrochloride
1year
Enrollment closed • Combination therapy • Metastases
|
docetaxel • Tevimbra (tislelizumab-jsgr) • irinotecan • sitravatinib (MGCD516)
1year
Neoadjuvant Sitravatinib in Combination With Nivolumab in Patients With Clear Cell Renal Cell Carcinoma (clinicaltrials.gov)
P2, N=25, Completed, Mirati Therapeutics Inc. | Active, not recruiting --> Completed
Trial completion • Combination therapy • IO biomarker • Metastases
|
PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD4 (CD4 Molecule) • CD27 (CD27 Molecule)
|
PD-L1 expression
|
Opdivo (nivolumab) • sitravatinib (MGCD516)
1year
Sitravatinib is a potential EGFR inhibitor and induce a new death phenotype in Glioblastoma. (PubMed, Invest New Drugs)
Our study also revealed that Sitravatinib effectively inhibited GBM invasive and induced DNA damage and cellular senescence. Furthermore, we observed a novel cell death phenotype induced by Sitravatinib, which differed from previously reported programmed death patterns such as apoptosis, pyroptosis, ferroptosis, and necrosis.
Journal
|
sitravatinib (MGCD516)
over1year
SAPPHIRE: Phase III study of sitravatinib plus nivolumab versus docetaxel in patients with previously treated advanced non-squamous non-small cell lung cancer (NSCLC) (ESMO 2023)
Conclusions The primary endpoint of OS was not met in pts with previously treated adv nsq NSCLC. Safety profiles for sitra/nivo and doce were consistent with prior reports for each regimen.
Clinical • P3 data • Late-breaking abstract • Metastases
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
Opdivo (nivolumab) • docetaxel • sitravatinib (MGCD516)
over1year
BGB-900-2003-IIT: A Study to Investigate the Efficacy and Safety of Tislelizumab Combined With Sitravatinib as Maintenance Therapy for ES-SCLC (clinicaltrials.gov)
P2, N=21, Recruiting, Zhejiang Cancer Hospital | N=59 --> 21 | Trial primary completion date: Dec 2024 --> Jul 2023
Enrollment change • Trial primary completion date
|
Tevimbra (tislelizumab-jsgr) • sitravatinib (MGCD516)
over1year
ITTACC: Tislelizumab in Combination With Sitravatinib for Recurrent/Metastatic Cervical Cancer After Platinum-Based Chemotherapy (clinicaltrials.gov)
P2, N=0, Withdrawn, Australia New Zealand Gynaecological Oncology Group | N=57 --> 0 | Trial completion date: Dec 2025 --> Jun 2023 | Initiation date: Mar 2023 --> Jun 2023 | Not yet recruiting --> Withdrawn | Trial primary completion date: Dec 2025 --> Jun 2023
Enrollment change • Trial completion date • Trial initiation date • Trial withdrawal • Trial primary completion date • Combination therapy • Metastases
|
Tevimbra (tislelizumab-jsgr) • sitravatinib (MGCD516)
over1year
Sitravatinib Plus Pembrolizumab in Patients With Advanced Treatment-Naïve PD-L1+ Non-Squamous NSCLC (clinicaltrials.gov)
P2, N=9, Active, not recruiting, Sarah Goldberg | Recruiting --> Active, not recruiting | N=70 --> 9
Enrollment closed • Enrollment change • Metastases
|
PD-L1 (Programmed death ligand 1)
|
Keytruda (pembrolizumab) • sitravatinib (MGCD516)
over1year
Enrollment open • Combination therapy • Metastases
|
ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
PD-L1 expression • ALK rearrangement
|
docetaxel • Tevimbra (tislelizumab-jsgr) • sitravatinib (MGCD516)