Regorafenib
- Generic Name
- Regorafenib
- Brand Names
- Stivarga
- Drug Type
- Small Molecule
- Chemical Formula
- C21H15ClF4N4O3
- CAS Number
- 755037-03-7
- Unique Ingredient Identifier
- 24T2A1DOYB
- Background
Regorafenib is an orally-administered inhibitor of multiple kinases. It is used for the treatment of metastatic colorectal cancer, advanced gastrointestinal stromal tumours, and hepatocellular carcinoma. FDA approved on September 27, 2012. Approved use of Regorafenib was expanded to treat Hepatocellular Carcinoma in April 2017.
- Indication
Regorafenib is indicated for the treatment of patients with metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy. Regorafenib is also indicated for the treatment of patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumour (GIST) who have been previously treated with imatinib mesylate and sunitinib malate. Regorafenib is also indicated for the treatment of patients with hepatocellular carcinoma (HCC) previously treated with sorafenib.
- Associated Conditions
- Hepatocellular Carcinoma, Metastatic Colorectal Cancer (CRC), Metastatic Gastrointestinal Stromal Tumor (GIST), Locally advanced Gastrointestinal stromal tumor, Unresectable Gastrointestinal stromal tumor
CytomX's CX-2051 Shows Promising 28% Response Rate in Advanced Colorectal Cancer Phase 1 Trial
• CytomX's EpCAM-targeting antibody-drug conjugate CX-2051 demonstrated a 28% confirmed response rate in late-line colorectal cancer patients, significantly outperforming current standard therapies with single-digit response rates.
• The novel PROBODY® masking technology appears to successfully target EpCAM, a previously "undruggable" tumor antigen, with manageable safety profile and no dose-limiting toxicities observed in the Phase 1 study.
• Median progression-free survival reached 5.8 months with 43% response rate at the highest dose level (10 mg/kg), supporting plans to advance to Phase 2 trials in first half of 2026.
SUNLIGHT Trial Highlights Importance of Sequential Therapies in Refractory Colorectal Cancer
• The SUNLIGHT trial demonstrated significant survival benefits when adding bevacizumab to trifluridine/tipiracil in refractory metastatic colorectal cancer, showing a 39% improvement in overall survival.
• Despite having three FDA-approved regimens for refractory colorectal cancer (trifluridine/tipiracil plus bevacizumab, fruquintinib, and regorafenib), many patients don't receive all available treatment options.
• Dr. John Marshall of Georgetown Lombardi Comprehensive Cancer Center emphasizes the need for personalized sequencing strategies and warns against non-medical factors influencing treatment decisions.
Study Reveals Factors Influencing Immune Checkpoint Inhibitor Efficacy in Metastatic Colorectal Cancer
• Cleveland Clinic and Moffitt Cancer Center researchers analyzed data from nearly 19,000 metastatic colorectal cancer patients, confirming immune checkpoint inhibitors significantly improve survival in MSI-H tumors compared to chemotherapy alone.
• The study identified specific factors that may enhance immune checkpoint inhibitor efficacy in traditionally unresponsive MSS tumors, including high albumin levels and recent antibiotic use, potentially expanding treatment options.
• Approximately 12.3% of patients with MSS tumors achieved durable responses to immune checkpoint inhibitors, suggesting the need for further research to identify biomarkers that could predict treatment success in this population.
Balstilimab Plus Botensilimab Shows Enhanced Response in MSS mCRC Without Liver Metastases
• Preliminary phase 2 data shows balstilimab combined with botensilimab yields a higher objective response rate in MSS mCRC patients without liver metastases.
• The combination of botensilimab 75 mg Q6W plus balstilimab showed a confirmed ORR of 19% and a disease control rate of 55%.
• The median duration of response has not been reached, with 70% of responses ongoing, indicating durable efficacy of the combination therapy.
• A phase 3 trial is planned using botensilimab 75 mg with balstilimab 240 mg, based on the favorable safety and efficacy profile observed.
FDA Approves Sotorasib Plus Panitumumab for KRAS G12C-Mutated Metastatic Colorectal Cancer
• The FDA has approved sotorasib (Lumakras) in combination with panitumumab (Vectibix) for treating KRAS G12C-mutated metastatic colorectal cancer in adults who have received prior chemotherapy.
• This approval is based on the Phase 3 CodeBreaK 300 trial, which demonstrated a significant improvement in progression-free survival compared to standard of care.
• The combination therapy led to a median progression-free survival of 5.6 months, a substantial increase compared to the 2 months observed with standard treatments.
• The FDA also approved the therascreen KRAS RGQ PCR Kit as a companion diagnostic to identify patients eligible for this targeted treatment approach.
Cytokinetics and Pyxis Oncology Announce Key Milestones for 2025; CytomX Prioritizes Pipeline
• Cytokinetics anticipates a pivotal year in 2025, focusing on the potential FDA approval and commercial launch of aficamten for obstructive hypertrophic cardiomyopathy (HCM) in the U.S.
• Pyxis Oncology is prioritizing the advancement of PYX-201, a novel antibody-drug conjugate (ADC), with data readouts expected in the second half of 2025 and the first half of 2026.
• CytomX Therapeutics is focusing on its lead program, CX-2051, an EpCAM-targeting PROBODY ADC for advanced metastatic colorectal cancer, with initial Phase 1a data expected in 1H 2025.
CSPC Pharma's Leuprorelin Injection and Regorafenib Tablets Approved for Clinical Trials and Treatment in China
• CSPC Pharmaceutical Group's Leuprorelin Extended-Release Injection has been approved for clinical trials in China for solid tumors, marking a significant advancement in long-acting GnRH agonists.
• The Leuprorelin injection offers potential benefits over existing treatments, including easier administration, reduced pain, and improved patient compliance due to its long-acting delivery technology.
• Regorafenib Tablets developed by CSPC have received drug registration approval in China for treating metastatic colorectal cancer, gastrointestinal stromal tumors, and hepatocellular carcinoma.
• The approval of Regorafenib Tablets enriches CSPC's oncology product portfolio and has passed the consistency evaluation of quality and efficacy of generic drugs.
Biomarker-Guided Therapies Transform Treatment Landscape Across Multiple Cancers
• Recent advances in targeted therapies including KRAS, BRAF, and CLDN18.2 inhibitors are revolutionizing treatment approaches for pancreatic, colorectal, lung and gastric cancers through molecular profiling-guided precision medicine.
• Zolbetuximab plus chemotherapy demonstrated significant survival benefits in CLDN18.2-positive gastric cancer, while KRAS inhibitors showed promising response rates of 20-45% in pancreatic cancer patients with specific mutations.
• Multiple biomarker-targeted approaches including HER2, PD-L1, and FGFR2 are expanding treatment options across gastrointestinal cancers, though optimal sequencing strategies are still being determined.
FDA Approves Bizengri for NRG1 Fusion-Positive Lung and Pancreatic Cancers
• The FDA has granted accelerated approval to Bizengri (zenocutuzumab-zbco) for advanced pancreatic adenocarcinoma and non-small cell lung cancer with NRG1 gene fusions.
• Bizengri is the first systemic therapy approved by the FDA specifically targeting NRG1 gene fusions in these cancers after prior systemic therapy.
• Clinical trial data showed overall response rates of 40% in pancreatic cancer and 33% in NSCLC, with manageable side effects, supporting the approval.
• This approval highlights the importance of biomarker testing to identify NRG1 fusions, enabling personalized treatment for these difficult-to-treat cancers.
Cyramza Plus Lonsurf Fails to Improve Overall Survival in Metastatic Colorectal Cancer
• The phase 3 IKF-AIO-RAMTAS trial showed that adding Cyramza to Lonsurf did not significantly improve overall survival in heavily pretreated metastatic colorectal cancer patients.
• Subgroup analysis revealed potential benefits in female patients and those with left-sided tumors, who experienced improved survival outcomes with the Cyramza/Lonsurf combination.
• While overall survival was not significantly extended, the combination of Cyramza and Lonsurf did demonstrate a significant improvement in progression-free survival.
• The combination therapy showed a manageable safety profile, though with a higher incidence of treatment-related side effects, particularly those associated with Cyramza.
ASCO 2024 Highlights: Key Updates in Cancer Therapies
• Bristol Myers Squibb's Opdivo/Yervoy combo demonstrated superior overall survival in first-line unresectable hepatocellular carcinoma compared to Lenvima or Nexavar.
• Sanofi's Sarclisa combination reduced the risk of death or disease progression by 40% in transplant-ineligible multiple myeloma patients.
• AstraZeneca and Daiichi Sankyo's Enhertu showed significant progression-free survival improvement versus chemotherapy in HER2-low breast cancer.
Drug Development Updates
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