Stivarga (regorafenib)

We present a 57-year-old man with KRAS G13D-mutant, liver-dominant metastatic rectal adenocarcinoma and recurrent fluoropyrimidine-associated coronary vasospasm precluding 5-fluorouracil and capecitabine. After multimodal first-line therapy and regorafenib, trifluridine/tipiracil (TAS-102) plus bevacizumab was initiated and integrated with liver-directed treatments for oligoprogressive disease. This combined strategy achieved approximately 16.6 months of disease control, substantially exceeding the median progression-free survival reported in the SUNLIGHT trial, with manageable hematological toxicity and preserved performance status. This case highlights the value of TAS-102 plus bevacizumab combined with focal liver-directed therapy as a feasible long-term strategy for selected patients with oligoprogressive mCRC when fluoropyrimidines cannot be used.

P1/2, N=73, Active, not recruiting, University of Southern California | Trial completion date: Jun 2026 --> Dec 2027

P2, N=0, Withdrawn, University of Miami | N=30 --> 0 | Recruiting --> Withdrawn

Temozolomide (TMZ) is the only approved first-line therapy, but frequent resistance limits its efficacy, highlighting the urgent need for alternative treatments...Using GBO-DST, FDA-approved drug screening identifies regorafenib and lazertinib as effective treatment alternatives. Additionally, lazertinib demonstrated superior efficacy to standard therapies in GBO transplantation mouse model. These findings underscore the potential of GBO-DST as a robust platform for precision oncology in glioblastoma.

P=N/A, N=715, Completed, Tongji Hospital

P1/2, N=36, Completed, Sun Yat-sen University | Trial completion date: Feb 2025 --> Mar 2026 | Trial primary completion date: Feb 2024 --> Mar 2026 | Active, not recruiting --> Completed

P2/3, N=60, Suspended, Centre Leon Berard | Recruiting --> Suspended

P2/3, N=255, Recruiting, Ningbo Newbay Technology Development Co., Ltd | Not yet recruiting --> Recruiting

P3, N=462, Completed, Australasian Gastro-Intestinal Trials Group | Active, not recruiting --> Completed

We confirmed that Regorafenib disrupts this entire axis and, in combination with anti-PD-1 therapy in ATC, overcomes immunosuppression to elicit potent anti-tumor immunity. Our studies revealed the GPI/O-GlcNAcylation/THBS1 signal as a master regulator of myeloid cell crosstalk and established a novel therapeutic strategy for targeting this metabolic checkpoint to potentiate ATC immunotherapy.

In zebrafish MASLD-HCC, PRS-OPT-nominated dosing reduced hepatic macrophage accumulation and improved disease-relevant transcriptional and morphological readouts. PRS-OPT enables interpretable, multi-objective dose nomination for MASLD-relevant HCC contexts, and establishes PRS-OPT as an interpretable, multi-objective framework for regimen nomination that is directly extensible to additional phenotypic endpoints for preclinical evaluation.

P2, N=31, Completed, The First Affiliated Hospital of Zhengzhou University