Stivarga (regorafenib)

P3, N=700, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: May 2028 --> Jul 2025 | Trial primary completion date: Jan 2025 --> Jul 2025

P2, N=72, Recruiting, Jules Bordet Institute | Trial completion date: Jan 2030 --> Dec 2030 | Trial primary completion date: Jan 2025 --> Jan 2026

P1/2, N=42, Active, not recruiting, Syndax Pharmaceuticals | Recruiting --> Active, not recruiting | N=158 --> 42

P=N/A, N=2326, Active, not recruiting, Bayer | Trial completion date: Oct 2024 --> Jan 2025 | Trial primary completion date: Oct 2024 --> Jan 2025

"The abstract will be released to the public on January 21, 2025 at 10:00 PM UTC"

P2, N=78, Completed, Australasian Gastro-Intestinal Trials Group | Active, not recruiting --> Completed

P1/2, N=325, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed

P1/2, N=2, Terminated, ImmunityBio, Inc. | Phase classification: P1b/2 --> P1/2 | N=332 --> 2 | Active, not recruiting --> Terminated; low enrollment

P2, N=31, Recruiting, Sarah K. Lynam MD | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

P2, N=127, Completed, Centre Oscar Lambret | Active, not recruiting --> Completed | Trial completion date: Mar 2025 --> Sep 2024

P2, N=14, Active, not recruiting, Case Comprehensive Cancer Center | Trial completion date: Oct 2024 --> Apr 2025 | Trial primary completion date: Oct 2024 --> Apr 2025

P2, N=163, Active, not recruiting, UNICANCER | Recruiting --> Active, not recruiting | Trial completion date: Mar 2026 --> Jun 2025 | Trial primary completion date: Sep 2025 --> Oct 2024

Combination treatment of regorafenib and oral methotrexate in patients with KRAS-mutant NSCLC was limited due to toxicity, and the study did not meet its primary end point. Computational modeling may aid in repurposing therapeutic options though caution must be exercised with tolerability.

Both patients were included in the REGOMUNE clinical trial, a phase I/II trial evaluating the combination of regorafenib with avelumab. HLH is a rare adverse effect of regorafenib that can be life-threatening. Therefore, clinicians should promptly consider this diagnosis when encountering manifestations consistent with HLH to ensure timely and appropriate management.

Inhibition of EGFR restores sensitivity to regorafenib, and the combination of gefitinib and regorafenib demonstrates significant antitumor efficacy both in vivo and in vitro. These findings suggest that this combination could be a potential strategy for patients with advanced HCC.

Postoperative treatment included radiotherapy and temozolomide...The recurrence was managed with regorafenib and bevacizumab, though complications like hand-foot syndrome and radiation necrosis arose...The novel FGFR3-FASN fusion suggests potential implications for GBM recurrence and lipid metabolism. Further studies are warranted to explore FGFR3-FASN's role in GBM and its therapeutic targeting.

In HCC cells, knockdown of DHFR or treatment with pralatrexate enhanced the sensitivity of HCC cells to molecularly targeted agents, such as sorafenib, regorafenib, lenvatinib, cabozantinib, or anlotinib...Therefore, pralatrexate upregulates the sensitivity of HCC cells to molecularly targeted drugs. These results expand our understanding of folate metabolism and HCC and can help provide more options for HCC treatment.

This review provides a comprehensive overview of the current state of BRAF-targeted therapies in melanoma, highlighting the efficacy and limitations of FDA-approved combinations of BRAF and MEK inhibitors such as vemurafenib, dabrafenib, trametinib, and cobimetinib...Recent studies on regorafenib, ERK5 signaling, and CD73 inhibition are highlighted as novel strategies to overcome resistance and improve treatment outcomes. The review also delves into the role of advanced therapeutic tools, such as mRNA vaccines and CRISPR-Cas9, in revolutionizing personalized oncology by targeting specific genetic mutations and enhancing immune responses against melanoma. The ongoing synergy between advancing research, targeted interventions, strategic treatment combinations, and cost-effectiveness evaluations offers a promising pathway to elevate patient outcomes in the persistent battle against melanoma significantly.

regorafenib is a multi-kinase inhibitor, and gastrointestinal perforation has been reported as a serious adverse event, although it is rare. We report a case of upper gastrointestinal perforation during regorafenib administration, with some discussion of the literature.

P2, N=0, Withdrawn, City of Hope Medical Center | N=84 --> 0 | Not yet recruiting --> Withdrawn

Over the past decade, regorafenib and trifluridine-tipiracil were the only available drugs and often provided limited clinical benefit compared to best supportive care. Results from subsequent practice-changing trials opened several novel therapeutic avenues, both for unselected patients (such as trifluridine-tipiracil plus bevacizumab or fruquintinib) and for subgroups defined by the presence of actionable alterations in their tumours (such as HER2-targeted therapies or KRASG12C inhibitors) or with no acquired mechanisms of resistance to the previously received targeted agents in circulating tumour DNA (such as retreatment with anti-EGFR antibodies). In this Review, we provide a comprehensive overview of advances in the field over the past few years and offer a practical perspective on translation of the most relevant results into the daily management of patients with metastatic colorectal cancer using an evidence-based algorithm. Finally, we discuss some of the most appealing ongoing areas of research and highlight approaches with the potential to further expand the therapeutic armamentarium.

P1/2, N=227, Active, not recruiting, Arcus Biosciences, Inc. | Trial completion date: Oct 2024 --> Jul 2025 | Trial primary completion date: Oct 2024 --> Jul 2025

Nitrosoureas (NS) such as lomustine and fotemustine and antiangiogenic drugs such as regorafenib(Reg) and bevacizumab (Bev) are all treatment options for rGBM. We concluded that pathogenic PTEN alteration may be a predictor of poor efficacy of regorafenib and lomustine in rGBM patients. However, a prospective study with a larger population is needed to better define the role of pTEN in these patient populations.

Background : Nitrosoureas (lomustine/fotemustine) and antiangiogenic drugs (bevacizumab or regorafenib) are second-line treatment options for patients with recurrent IDHwt-glioblastoma (rGBM). The multi-classification ML model developed in this study was able to identify clinical and molecular signatures of recurrent glioblastoma patients responding to specific second-line treatment with bevacizumab or regorafenib or nitrosoureas.

In conclusion, this study provides a novel, real-world reference for survival outcomes in patients with metastatic GIST.

P4, N=110, Active, not recruiting, Rennes University Hospital | Trial primary completion date: Sep 2024 --> Jun 2025

P2, N=8, Active, not recruiting, Dana-Farber Cancer Institute

P1/2, N=380, Not yet recruiting, Shanghai Runshi Pharmaceutical Technology Co., Ltd

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

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.

ARHGAP12 expression is elevated in HCC and TKI-resistant HCC, and its regulatory role in FA may underlie the TKI-resistant phenotype.

P3, N=94, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Nov 2025 --> Feb 2025

P3, N=505, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Nov 2025 --> Feb 2025

P3, N=480, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

Ultimately, regorafenib significantly inhibits tumor growth in vivo. In conclusion, our finding demonstrated that regorafenib promotes antitumor progression in melanoma by reducing RRM2.

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.

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

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.

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.

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.

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

P1/2, N=219, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed | N=494 --> 219 | Trial completion date: May 2025 --> Aug 2024