^
2d
Trial completion date • Trial primary completion date
|
Stivarga (regorafenib)
2d
New P1/2 trial
|
cisplatin • carboplatin • paclitaxel • everolimus • Stivarga (regorafenib) • etoposide IV • SYHA1813
3d
Regorafenib in Patients with Progressive, Recurrent/Metastatic Adenoid Cystic Carcinoma (clinicaltrials.gov)
P2, N=38, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Mar 2025 --> Nov 2024 | Trial primary completion date: Mar 2025 --> Nov 2024
Trial completion • Trial completion date • Trial primary completion date • Metastases
|
Stivarga (regorafenib)
10d
Osteosarcoma cells depend on MCL-1 for survival, and osteosarcoma metastases respond to MCL-1 antagonism plus regorafenib in vivo. (PubMed, BMC Cancer)
Chemotherapy, consisting of doxorubicin, cisplatin and methotrexate (MAP) increased the 5-year osteosarcoma survival rate from 20% to approximately 60% by the 1980s...Patients whose disease fails to respond to MAP receive second-line treatments such as etoposide and, in more recent years, the kinase inhibitor regorafenib...Importantly, we found that inhibition of MCL-1 with the BH3-mimetic S63845 combined with regorafenib significantly prolonged the survival of mice bearing pulmonary osteosarcoma metastases. Together, our results highlight the importance of MCL-1 in osteosarcoma cell survival and present a potential therapeutic avenue that may improve metastatic osteosarcoma patient outcomes.
Preclinical • Journal
|
BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1)
|
cisplatin • doxorubicin hydrochloride • Stivarga (regorafenib) • etoposide IV • methotrexate • S63845
15d
Clinical significance of upregulated Rho GTPase activating protein 12 causing resistance to tyrosine kinase inhibitors in hepatocellular carcinoma. (PubMed, World J Gastrointest Oncol)
ARHGAP12 expression is elevated in HCC and TKI-resistant HCC, and its regulatory role in FA may underlie the TKI-resistant phenotype.
Journal • IO biomarker
|
ITGA6 (Integrin, alpha 6) • ITGB1 (Integrin Subunit Beta 1)
|
sorafenib • Cabometyx (cabozantinib tablet) • Stivarga (regorafenib)
16d
Trial completion date • Metastases
|
Keytruda (pembrolizumab) • Stivarga (regorafenib) • Lonsurf (trifluridine/tipiracil) • favezelimab/pembrolizumab (MK-4280A)
16d
Trial completion date • Metastases
|
Keytruda (pembrolizumab) • Stivarga (regorafenib) • Lonsurf (trifluridine/tipiracil) • favezelimab/pembrolizumab (MK-4280A)
17d
Trial completion • Combination therapy • Metastases
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability)
|
BRAF V600E • MSI-H/dMMR • BRAF V600 • KRAS wild-type • RAS wild-type • NRAS wild-type
|
Keytruda (pembrolizumab) • Lenvima (lenvatinib) • Stivarga (regorafenib) • Lonsurf (trifluridine/tipiracil)
23d
Regorafenib promotes antitumor progression in melanoma by reducing RRM2. (PubMed, iScience)
Ultimately, regorafenib significantly inhibits tumor growth in vivo. In conclusion, our finding demonstrated that regorafenib promotes antitumor progression in melanoma by reducing RRM2.
Journal • PARP Biomarker
|
BAX (BCL2-associated X protein) • RRM2 (Ribonucleotide Reductase Regulatory Subunit M2) • E2F3 (E2F transcription factor 3)
|
Stivarga (regorafenib)
29d
The correlation between cellular O-GlcNAcylation and sensitivity to O-GlcNAc inhibitor in colorectal cancer cells. (PubMed, PLoS One)
Furthermore, we demonstrated that Os exhibited a synergistic relationship with regorafenib (Re)...Finally, we showed that the Os:Re combination suppressed the growth of NCI-H508 tumor spheroids. Overall, our findings highlighted OGTi as a potential anticancer agent that could be used in combination with other molecules to enhance the efficacy while minimizing adverse effects, and identified total cellular O-GlcNAcylation as a potential predictive marker for OGTi sensitivity.
Journal
|
OGT (O-linked N-acetylglucosamine (GlcNAc) transferase)
|
Stivarga (regorafenib)
1m
COLONGER: An Observational Study to Learn More About the Long-Term Responses to Treatment With Regorafenib in Patients With Metastatic Colorectal Cancer in the United States (clinicaltrials.gov)
P=N/A, N=2326, Active, not recruiting, Bayer | Completed --> Active, not recruiting | Trial completion date: Oct 2023 --> Oct 2024 | Trial primary completion date: Oct 2023 --> Oct 2024
Enrollment closed • Trial completion date • Trial primary completion date • Real-world evidence • Real-world • Metastases
|
Stivarga (regorafenib)
1m
TAS-102 (trifluridine/tipiracil) plus bevacizumab versus TAS-102 alone as salvage treatment options for metastatic colorectal cancer in routine clinical practice. (PubMed, Front Oncol)
The number of patients with prior regorafenib treatment was 14 in the TAS-102 with bevacizumab group and 5 in the TAS-102 alone group. The combination of TAS-102 and bevacizumab resulted in a better survival outcome than TAS-102 monotherapy, consistent with previous studies. This analysis supports the use of the combination of TAS-102 and bevacizumab as the best therapeutic option for patients with refractory metastatic colorectal cancer in clinical practice.
Journal • Metastases
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • RAS mutation • KRAS G12
|
Avastin (bevacizumab) • Stivarga (regorafenib) • Lonsurf (trifluridine/tipiracil)
1m
TRIM21 induces selective autophagic degradation of c-Myc and sensitizes regorafenib therapy in colorectal cancer. (PubMed, Proc Natl Acad Sci U S A)
Targeting TRIM21 to disrupt KRAS/MT-driven phosphorylation using the antidepressant vilazodone shows potential for enhancing the efficacy of regorafenib in treating KRAS-mutant CRC in preclinical models. These findings are instrumental for KRAS-mutant CRC treatment aiming at activating TRIM21-mediated selective autophagic degradation of c-Myc.
Journal
|
KRAS (KRAS proto-oncogene GTPase) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • TRIM21 (Tripartite Motif Containing 21)
|
KRAS mutation
|
Stivarga (regorafenib)
1m
Pan-Canadian consensus recommendations for GIST management in high- and low-throughput centres across Canada. (PubMed, Ther Adv Med Oncol)
This literature review, along with clinical expertise and opinion, was used to develop this concise and clinically relevant consensus paper to harmonize the knowledge and clinical practice on GIST management across Canada. The content presented here will help guide healthcare providers, especially in Canada, in terms of approaching and managing GIST.
Review • Journal
|
PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
|
PDGFRA mutation
|
imatinib • sunitinib • Stivarga (regorafenib) • Ayvakit (avapritinib) • Qinlock (ripretinib)
1m
Regorafenib and Pembrolizumab in Treating Participants With Advanced or Metastatic Colorectal Cancer (clinicaltrials.gov)
P1/2, N=75, Active, not recruiting, University of Southern California | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2024 --> Jun 2025
Trial completion date • Trial primary completion date
|
Keytruda (pembrolizumab) • Stivarga (regorafenib)
1m
An Investigational Immunotherapy Study of BMS-986288 Alone and in Combination With Nivolumab in Advanced Solid Cancers (clinicaltrials.gov)
P1/2, N=219, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed | N=494 --> 219 | Trial completion date: May 2025 --> Aug 2024
Trial completion • Enrollment change • Trial completion date • Combination therapy • Metastases
|
Opdivo (nivolumab) • Stivarga (regorafenib) • BMS-986288
1m
[18F]FLT-PET as a Predictive Imaging Biomaker of Treatment Responses to Regorafenib (clinicaltrials.gov)
P=N/A, N=68, Completed, Asan Medical Center | Unknown status --> Completed
Trial completion
|
Stivarga (regorafenib)
1m
Phase 2 trial of regorafenib in recurrent or metastatic adenoid cystic carcinoma. (PubMed, Clin Cancer Res)
The trial failed to meet the pre-specified 6-month PFS and BOR targets. We hypothesize that TKI efficacy may be reliant upon an interplay between kinase inhibition and the ACC immune microenvironment, while programs promoting cell cycle progression may contribute to TKI resistance. These observations suggest that trials evaluating CDK4/6 inhibition plus a VEGFR-TKI should be considered.
P2 data • Journal • Metastases
|
NOTCH1 (Notch 1) • KDM6A (Lysine Demethylase 6A)
|
Stivarga (regorafenib)
2ms
Schisandrin C prevents Regorafenib-Induced cardiotoxicity by recovering EPHA2 expression in cardiomyocytes. (PubMed, Toxicol Sci)
In addition, we showed that recovering EPHA2 expression via plasmid-induced overexpression of EPHA2 or schisandrin C, a natural product, could prevent regorafenib-induced cardiotoxicity. These findings demonstrated that regorafenib causes cardiomyocyte apoptosis and cardiac injury by reducing the expression of EPHA2 and schisandrin C could prevent regorafenib-induced cardiotoxicity by recovering EPHA2 expression, which provides a potential management strategy for regorafenib-induced cardiotoxicity and will benefit the safe application of regorafenib in clinic.
Journal
|
EPHA2 (EPH receptor A2)
|
EPHA2 overexpression
|
Stivarga (regorafenib)
2ms
Regorafenib for Recurrent Grade 2 and 3 Meningioma (MIRAGE Trial) (clinicaltrials.gov)
P2, N=104, Recruiting, Istituto Oncologico Veneto IRCCS | Not yet recruiting --> Recruiting
Enrollment open
|
BRAF (B-raf proto-oncogene)
|
Stivarga (regorafenib)
2ms
Enrollment closed • Enrollment change • Metastases
|
PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene)
|
BRAF wild-type
|
Stivarga (regorafenib) • balstilimab (AGEN2034) • botensilimab (AGEN1181)
2ms
Enrollment change
|
Stivarga (regorafenib)
2ms
Study Of Intrabucally Administered Electromagnetic Fields and Regorafenib (clinicaltrials.gov)
P2, N=2, Terminated, Wake Forest University Health Sciences | N=25 --> 2 | Trial completion date: Nov 2025 --> May 2024 | Suspended --> Terminated | Trial primary completion date: May 2025 --> May 2024; Slow accruals
Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Metastases
|
Stivarga (regorafenib)
2ms
Trial primary completion date • Combination therapy • Metastases
|
Loqtorzi (toripalimab-tpzi) • Stivarga (regorafenib)
2ms
NEXT-REGIRI: Assessing a Regorafenib-irinotecan Combination Versus Regorafenib Alone in Metastatic Colorectal Cancer Patients (clinicaltrials.gov)
P3, N=66, Active, not recruiting, Institut du Cancer de Montpellier - Val d'Aurelle | Recruiting --> Active, not recruiting
Enrollment closed • Metastases
|
CCND1 (Cyclin D1)
|
RAS wild-type
|
Stivarga (regorafenib) • irinotecan
2ms
New P2 trial
|
Avastin (bevacizumab) • Tecentriq (atezolizumab) • Tyvyt (sintilimab) • Stivarga (regorafenib)
2ms
TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer (clinicaltrials.gov)
P2, N=3791, Recruiting, American Society of Clinical Oncology | Trial completion date: Dec 2025 --> Jun 2027 | Trial primary completion date: Dec 2024 --> Jun 2026
Trial completion date • Trial primary completion date • Tumor mutational burden • Metastases
|
BRAF (B-raf proto-oncogene)
|
FoundationOne® CDx
|
Keytruda (pembrolizumab) • Opdivo (nivolumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Yervoy (ipilimumab) • Ibrance (palbociclib) • Zelboraf (vemurafenib) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • sunitinib • Perjeta (pertuzumab) • Cotellic (cobimetinib) • Talzenna (talazoparib) • Verzenio (abemaciclib) • Stivarga (regorafenib) • Lytgobi (futibatinib) • Tukysa (tucatinib) • Torisel (temsirolimus) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
2ms
Fibroblast Growth Factor 2 (FGF2) Activates Vascular Endothelial Growth Factor (VEGF) Signaling in Gastrointestinal Stromal Tumors (GIST): An Autocrine Mechanism Contributing to Imatinib Mesylate (IM) Resistance. (PubMed, Cancers (Basel))
This also resulted in significant synergy between BGJ 398 and VEGFR inhibitors (i.e., sunitinib and regorafenib) by enhancing their pro-apoptotic and anti-proliferative activities. Mechanistically, the FGF2-induced activation of the FGFR pathway turns on VEGFR signaling via the overproduction of VEGF-A, induces the interaction between FGFR1/2 and VEGFR1, and thereby renders cancer cells highly sensitive to the dual inhibition of the aforementioned RTKs. Thus, our data uncovers the novel mechanism of the cross-talk between the aforementioned RTKs in IM-resistant GISTs lacking secondary KIT mutations and suggests that the dual blockade of FGFR and VEGFR signaling might be an effective treatment strategy for patients with GIST-acquired IM resistance via KIT-independent mechanisms.
Journal • Stroma
|
FGFR1 (Fibroblast growth factor receptor 1) • FLT1 (Fms-related tyrosine kinase 1) • FGF2 (Fibroblast Growth Factor 2)
|
KIT mutation • FGFR1 expression • FLT1 expression
|
imatinib • sunitinib • Stivarga (regorafenib) • Truseltiq (infigratinib)
2ms
Identification of microenvironment features associated with primary resistance to anti-PD-1/PD-L1 + antiangiogenesis in gastric cancer through spatial transcriptomics and plasma proteomics. (PubMed, Mol Cancer)
We report the results of the REGOMUNE phase II study, in which Caucasian patients were administered regorafenib, a multi-tyrosine kinase inhibitor, in combination with avelumab, a PD-L1-targeting monoclonal antibody. Additionally, peripheral biomarker assessments identified elevated levels of cytokines, including CSF-1, IL-4, IL-8, and TWEAK, correlating with adverse clinical outcomes, thereby accentuating the role of macrophage infiltration in mediating resistance. These insights furnish an invaluable foundation for elucidating, and potentially circumventing, resistance mechanisms in current AGC therapeutic paradigms, emphasizing the integral role of tumor microenvironmental dynamics and immune modulation.
Journal • PD(L)-1 Biomarker • IO biomarker
|
CXCL8 (Chemokine (C-X-C motif) ligand 8) • CSF1 (Colony stimulating factor 1) • IL4 (Interleukin 4)
|
CXCL8 elevation • S100A10 overexpression
|
Bavencio (avelumab) • Stivarga (regorafenib)
2ms
Small HBV surface antigen drives regorafenib resistance in HCC via KIAA1429-dependent m6A modification of CCR9. (PubMed, J Med Virol)
A substantial body of literature, including our own, points to a connection between hepatitis B virus (HBV) infection and the development of drug resistance in hepatocellular carcinoma (HCC), particularly against sorafenib. In conclusion, SHBs promoted HCC progression and regorafenib resistance via KIAA1429-mediated m6A modification of CCR9. Our findings suggested that CCR9 could be a potential prognostic biomarker and a valuable molecular therapeutic target of regorafenib resistance in HBV-related HCC.
Journal
|
ABCB1 (ATP Binding Cassette Subfamily B Member 1) • ABCC1 (ATP Binding Cassette Subfamily C Member 1) • VIRMA (Vir Like M6A Methyltransferase Associated)
|
sorafenib • Stivarga (regorafenib)
2ms
Exploratory Study Identifies Matrix Metalloproteinase-14 and -9 as Potential Biomarkers of Regorafenib Efficacy in Metastatic Colorectal Cancer. (PubMed, Cancers (Basel))
These findings were not observed in the control cohort. Our study suggests MMP-14 and MMP-9 may serve as prognostic markers for regorafenib and provide insights into novel combination therapies with anti-MMP-9 agents or FTD/TPI.
Journal • Metastases
|
MMP9 (Matrix metallopeptidase 9) • MMP14 (Matrix Metallopeptidase 14)
|
Stivarga (regorafenib) • Lonsurf (trifluridine/tipiracil)
3ms
New P2 trial • Metastases
|
Stivarga (regorafenib) • balstilimab (AGEN2034) • botensilimab (AGEN1181)
3ms
Regorafenib Enhances the Efficacy of Photodynamic Therapy in Hepatocellular carcinoma through MAPK Signaling Pathway Suppression. (PubMed, Photodiagnosis Photodyn Ther)
The body weight and HE staining of normal organs primarily indicated the safety of this combined strategy. These results indicate that the combination of Regorafenib and Lipo-Ce6 can significantly enhance the anti-tumor efficiency of PDT for HCC and exhibits good biosafety.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • BAX (BCL2-associated X protein) • CASP3 (Caspase 3)
|
Stivarga (regorafenib)
3ms
Recent advancements in the small-molecule drugs for hepatocellular carcinoma (HCC): Structure-activity relationships, pharmacological activities, and the clinical trials. (PubMed, Biomed Pharmacother)
By revealing their structure-activity relationships, pharmacological actions, and clinical trials, small-molecule drugs can offer broad prospects for the development of new medications.
Review • Journal
|
EGFR (Epidermal growth factor receptor) • FGFR (Fibroblast Growth Factor Receptor)
|
sorafenib • Lenvima (lenvatinib) • Cabometyx (cabozantinib tablet) • Stivarga (regorafenib)
3ms
Interaction of Purine and its Derivatives with A1, A2-Adenosine Receptors and Vascular Endothelial Growth Factor Receptor-1 (Vegf-R1) as a Therapeutic Alternative to Treat Cancer. (PubMed, Drug Res (Stuttg))
Besides, adenosine, cgs-15943, rolofylline, cvt-124, wrc-0571, luf-5834, cvt-6883, AZD-4635, cabozantinib, pazopanib, regorafenib, and sorafenib drugs were used as controls...Besides, the inhibition constants (Ki) values for purine and their derivatives 5: , 9: , 10: , 14: , 15: , 16: , and 20: were lower compared with the controls Theoretical data suggest that purine and their derivatives 5: , 9: , 10: , 14: , 15: , 16: , and 20: could produce changes in cancer cell growth through inhibition of A1, A2-adenosine receptors and VEGFR-1 inhibition. These data indicate that these purine derivatives could be a therapeutic alternative to treat some types of cancer.
Journal
|
VEGFA (Vascular endothelial growth factor A) • FLT1 (Fms-related tyrosine kinase 1)
|
sorafenib • pazopanib • Cabometyx (cabozantinib tablet) • Stivarga (regorafenib) • imaradenant (AZD4635)
3ms
Clinical predictive factors of the efficacy of immune checkpoint inhibitors and kinase inhibitors in advanced hepatocellular cancer. (PubMed, Clin Transl Oncol)
PLR and TC were potential clinical predictive factors for survival outcomes in patients with advanced HCC who received ICI/kinase inhibitor combination therapy. It is important to know the clinical characteristics of patients prior to treatment initiation to optimize outcomes.
Journal • Checkpoint inhibition • IO biomarker • Metastases
|
AFP (Alpha-fetoprotein)
|
Stivarga (regorafenib)
3ms
Enrollment change • Trial completion date • Combination therapy • Metastases
|
Opdivo (nivolumab) • Mekinist (trametinib) • Yervoy (ipilimumab) • Stivarga (regorafenib)
3ms
New P2 trial • Combination therapy • Checkpoint inhibition • IO biomarker • Metastases
|
CD8 (cluster of differentiation 8) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CD4 (CD4 Molecule) • IL2 (Interleukin 2)
|
Stivarga (regorafenib)
3ms
Regorafenib Attenuates Osteoclasts Differentiation by Inhibiting the NF-κB, NFAT, ERK, and p38 Signaling Pathways. (PubMed, ACS Omega)
These results indicate that regorafenib exerts its protective effects against osteoclast-related osteolytic disease by inhibiting the RANKL-induced NF-κB, NFAT, ERK, and p38 signaling pathways. This study proves that regorafenib may serve as a potential therapeutic agent for osteoclast-related osteolytic diseases.
Journal
|
CASP3 (Caspase 3) • MMP9 (Matrix metallopeptidase 9) • MAPK14 (Mitogen-Activated Protein Kinase 14) • MAPK3 (Mitogen-Activated Protein Kinase 3)
|
Stivarga (regorafenib)
3ms
ctDNA-guided Treatment of TKI Plus PD-1 Inhibitor for Advanced pMMR/MSS Colorectal Cancer (clinicaltrials.gov)
P2, N=68, Recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
New P2 trial • Circulating tumor DNA • Metastases
|
BRAF (B-raf proto-oncogene)
|
Tyvyt (sintilimab) • Stivarga (regorafenib) • Fruzaqla (fruquintinib)
3ms
Regorafenib for Recurrent Grade 2 and 3 Meningioma (MIRAGE Trial) (clinicaltrials.gov)
P2, N=104, Not yet recruiting, Istituto Oncologico Veneto IRCCS | Initiation date: Jun 2024 --> Sep 2024
Trial initiation date
|
BRAF (B-raf proto-oncogene)
|
Stivarga (regorafenib)
3ms
RePERSO: Evaluation of Treatment PERSOnalization Based on Its Therapeutic Monitoring in Patients With Metastatic Colorectal Cancer Treated With REgorafenib (clinicaltrials.gov)
P4, N=110, Active, not recruiting, Rennes University Hospital | Recruiting --> Active, not recruiting | Trial completion date: May 2025 --> Dec 2025
Enrollment closed • Trial completion date • Metastases
|
BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability)
|
Stivarga (regorafenib)