Stivarga (regorafenib)

P2, N=40, Completed, Asan Medical Center | Recruiting --> Completed

P2/3, N=2250, Recruiting, Global Coalition for Adaptive Research | N=1280 --> 2250

P1/2, N=48, Recruiting, Asan Medical Center | Not yet recruiting --> Recruiting

PRS was used to optimize GACC-metformin-regorafenib combinations...In zebrafish xenografts, GACC (50 µM) reduced Hep3B tumor fluorescence by ~90% without detectable hepatotoxicity, whereas sorafenib decreased liver size/fluorescence...PRS identified an off-grid triple combination that reduced PLC/PRF/5 viability to 19% while maintaining THLE-2 viability at 52% and preserving zebrafish development. GACC is a G4-active cobalt-glutamate scaffold with anti-HCC activity and favorable zebrafish safety, and a zebrafish-plus-PRS workflow enables rational, less toxic combination design.

Molecular docking further supported these findings, showing favorable binding energy (-7.98 kcal/mol) compared to regorafenib (-7.13 kcal/mol). Collectively, these results highlight PL-13 as a promising lead compound for further optimization toward CRC therapy.

P2, N=80, Recruiting, Sun Yat-sen University

AP4-43 demonstrates increased efficacy in the Drosophila model and greater potency than regorafenib in a mammalian CRC organoid growth assay. Functional analysis indicates AP4-43 acts as a multi-kinase inhibitor, with its enhanced activity associated with the inhibition of a network including CLK1 and NEK4. This work demonstrates the utility of a digital synthesis platform for generating and optimising lead compounds in a complex, preclinical drug discovery context.

In this large real-world cohort of patients with mCRC, FTD-TPI + bevacizumab was associated with improved PFS and DCR compared with FTD-TPI or regorafenib, with consistent benefit across most molecular subgroups, including KRASG12 mutations.

P2, N=146, Not yet recruiting, Asan Medical Center

P2, N=72, Active, not recruiting, Jules Bordet Institute | Recruiting --> Active, not recruiting | Trial completion date: Dec 2030 --> Dec 2032 | Trial primary completion date: Jan 2026 --> Dec 2026

P2, N=30, Recruiting, University of Miami | Trial completion date: Jan 2031 --> May 2031 | Trial primary completion date: Jan 2031 --> May 2031

Rectal cancer recurrence remains a major therapeutic challenge, particularly in patients unresponsive to conventional regimens. While previous studies have demonstrated limited benefit of immunotherapy in this tumor subtype, the present findings suggest an emerging therapeutic opportunity that warrants prospective evaluation to confirm efficacy, explore the mechanistic basis, and identify biomarkers predictive of durable response beyond the absence of liver metastases. More effective combinatorial regimens like zanzalintinib and atezolizumb (STELLAR-303) trial, as well as newer generation of CTLA-4 inhibitors like botensilimab, vilastobart, and muzastotug are showing more promise for patients with MSS colorectal cancers in particular who do not have liver metastases (NLM).