Stivarga (regorafenib)

P2, N=21, Completed, First Affiliated Hospital, Sun Yat-Sen University | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=39, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027

P=N/A, N=121, Completed, Bayer | Active, not recruiting --> Completed | N=200 --> 121

High positive rates of CD3+, CD3+CD8+, CD3+CD8-, and PD-1+CD3+ T cells in the stroma area correlated with prolonged progression-free survival and favorable disease control; however, neither the positive rate of PD-L1 cells nor the density of it in the tumor area was associated with survival and response. In this combination-therapy-focused multi-omics analysis integrating tissue genomics, ctDNA features/dynamics and TME profiling, we identified ctDNA maxAF, HAF-bTMB, bITH, HAF-bITH, mutational status of SMAD4 or PIK3CA and TME markers as predictive or prognostic biomarkers for regorafenib plus toripalimab in refractory mCRC.

Patients with liver metastases exhibited T cell senescence and metabolic hyperactivation, correlating with therapeutic resistance. These findings highlight that pre-existing tumor immunogenicity and T cell functional capacity are associated with response to RIN therapy, and that RIN treatment may facilitate both systemic T cell activation and local TME modulation.

By blocking the mechanisms that lead to angiogenesis and tumor growth, first-line systemic treatments, such the multi-tyrosine kinase inhibitors (TKIs) lenvatinib and sorafenib, have shown moderate improvements in survival. However, their long-term efficacy is significantly reduced by intrinsic and acquired resistance, which is why second-line medications like regorafenib, cabozantinib, and ramucirumab are being studied. When combined with anti-VEGF treatments, parallel developments in immunotherapy, in particular immune checkpoint inhibitors (ICIs) such as atezolizumab and nivolumab, have shown promising outcomes...In the end, the review promotes the combination of dynamic molecular profiling and biomarker-driven precision medicine to enhance patient stratification, improve treatment decision-making, and provide long-lasting clinical effects. A strategic foundation for future advancements and individualized treatment of hepatocellular carcinoma is provided by this comprehensive synthesis.

P2/3, N=437, Active, not recruiting, Children's Oncology Group | Trial completion date: Jul 2032 --> Dec 2027 | Trial primary completion date: Jul 2032 --> Dec 2027

P2, N=16, Suspended, M.D. Anderson Cancer Center | Not yet recruiting --> Suspended

In vivo, H22 tumor‑bearing mice treated with the combination exhibited suppressed tumor growth without systemic toxicity, along with changes in apoptotic proteins, enhanced tumor‑infiltrating immune cells and improved systemic immune responses. These findings indicated that the combination exerts enhanced suppression of HCC by inhibiting STAT3 and remodeling anti‑tumor immunity, providing preclinical evidence for a safe and effective strategy.

Consistent with the longer doubling time, PDES were more resistant to doxorubicin, etoposide and vincristine and ionising radiation (p < 0.0001) than cell lines. PDES were sensitive to mTKIs (cabozantinib, lenvatinib, and regorafenib), and trabectedin. The response of PDES to drugs in vitro reflects the clinical experience of patients. Models incorporating PDES cells may positively contribute to the preclinical pipeline.

Drug sensitivity analysis revealed that the high-risk group was more sensitive to fluorouracil and gemcitabine (P<0.001), whereas the low-risk group showed better responses to regorafenib (P=0.007). This study establishes a novel prognostic model for COAD based on cofactor and vitamin metabolism, enabling precise survival prediction and guiding personalized therapeutic strategies. The model underscores the interplay between metabolic-immune crosstalk and chemotherapy response heterogeneity, providing a framework for developing targeted metabolic therapies combined with immune modulation.