zanzalintinib (XL092)

P2, N=20, Suspended, M.D. Anderson Cancer Center | Not yet recruiting --> Suspended

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).

P3, N=758, Not yet recruiting, Merck Sharp & Dohme LLC

P2, N=26, Not yet recruiting, UNC Lineberger Comprehensive Cancer Center

P3, N=904, Recruiting, Merck Sharp & Dohme LLC

P2, N=12, Not yet recruiting, M.D. Anderson Cancer Center

P3, N=904, Recruiting, Merck Sharp & Dohme LLC

P2, N=70, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting

P2, N=100, Not yet recruiting, Exelixis

P2/3, N=398, Recruiting, Merck Sharp & Dohme LLC

P2/3, N=172, Not yet recruiting, Exelixis Inc.

Emerging clinical and translational data indicate that disrupting this axis can sensitize MSS-CRC to ICIs: for example, Zanzalintinib combined with Atezolizumab reported survival benefit in the STELLAR-303 trial, and dual blockade of novel checkpoints with PD-(L)1 has been associated with enhanced immune activation in solid tumors. Targeting the MDSC-Treg axis therefore represents a promising strategy to overcome immunotherapy resistance in MSS/pMMR CRC.