Zanzalintinib

Zanzalintinib
Clinical data
Other names	XL092
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name 1-N′-(4-Fluorophenyl)-1-N-[4-[7-methoxy-6-(methylcarbamoyl)quinolin-4-yl]oxyphenyl]cyclopropane-1,1-dicarboxamide;
CAS Number	2367004-54-2;
PubChem CID	139350422;
ChemSpider	114641993;
UNII	KC2JC2ZA04;
Chemical and physical data
Formula	C29H25FN4O5
Molar mass	528.540 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CNC(=O)C1=CC2=C(C=CN=C2C=C1OC)OC3=CC=C(C=C3)NC(=O)C4(CC4)C(=O)NC5=CC=C(C=C5)F;
	InChI InChI=1S/C29H25FN4O5/c1-31-26(35)22-15-21-23(16-25(22)38-2)32-14-11-24(21)39-20-9-7-19(8-10-20)34-28(37)29(12-13-29)27(36)33-18-5-3-17(30)4-6-18/h3-11,14-16H,12-13H2,1-2H3,(H,31,35)(H,33,36)(H,34,37); Key:JSPCKALGNNVYOO-UHFFFAOYSA-N;

Zanzalintinib (also known as XL092) is an inhibitor of several receptor tyrosine kinases, including VEGFR2, MET, and the TAM kinases AXL and MERTK. It could potentially be used to treat colorectal cancer and renal cell carcinoma (RCC). It is being developed by Exelixis.^[1]^[2]

STELLAR-303 is a phase 3, randomized trial of zanzalintinib in combination with atezolizumab versus regorafenib in previously treated metastatic colorectal cancer.^[3] The trial found that the combination of zanzalintinib and atezolizumab improved overall survival compared to regorafenib.^[4]

STELLAR-304 (NCT05678673) is a phase 3, randomized trial of zanzalintinib in combination with nivolumab versus sunitinib in patients with advanced or metastatic non-clear cell renal cell carcinoma (nccRCC).^[5]

References

^ Sharma MR, Subbiah V, Shapiro G, Pal SK, Agarwal N, Wentzel K, et al. (September 2022). "481P A phase I first-in-human study of XL092 in patients (pts) with locally advanced or metastatic solid tumors: Results from dose-escalation of XL092 alone and in combination with atezolizumab". Annals of Oncology. 33: S760. doi:10.1016/j.annonc.2022.07.609. ISSN 0923-7534.
^ "Stellar 002". STELLAR Clinical Trials Program (Exelixis). Official US HCP Website. Retrieved 2024-01-09.
^ "Stellar 303". STELLAR Clinical Trials Program (Exelixis). Official US HCP Website. Retrieved 2024-01-09.
^ Hecht JR, Park YS, Tabernero J, Lee MA, Lee S, Virgili AC, et al. (November 2025). "Zanzalintinib plus atezolizumab versus regorafenib in refractory colorectal cancer (STELLAR-303): a randomised, open-label, phase 3 trial". Lancet. 406 (10517): 2360–2370. doi:10.1016/S0140-6736(25)02025-2. hdl:2078.1/311863. PMID 41130252.
^ "Stellar 304". STELLAR Clinical Trials Program (Exelixis). Official US HCP Website. Retrieved 2024-01-09.

[1] Sharma MR, Subbiah V, Shapiro G, Pal SK, Agarwal N, Wentzel K, et al. (September 2022). "481P A phase I first-in-human study of XL092 in patients (pts) with locally advanced or metastatic solid tumors: Results from dose-escalation of XL092 alone and in combination with atezolizumab". Annals of Oncology. 33: S760. doi:10.1016/j.annonc.2022.07.609. ISSN 0923-7534.

[2] "Stellar 002". STELLAR Clinical Trials Program (Exelixis). Official US HCP Website. Retrieved 2024-01-09.

[3] "Stellar 303". STELLAR Clinical Trials Program (Exelixis). Official US HCP Website. Retrieved 2024-01-09.

[4] Hecht JR, Park YS, Tabernero J, Lee MA, Lee S, Virgili AC, et al. (November 2025). "Zanzalintinib plus atezolizumab versus regorafenib in refractory colorectal cancer (STELLAR-303): a randomised, open-label, phase 3 trial". Lancet. 406 (10517): 2360–2370. doi:10.1016/S0140-6736(25)02025-2. hdl:2078.1/311863. PMID 41130252.

[5] "Stellar 304". STELLAR Clinical Trials Program (Exelixis). Official US HCP Website. Retrieved 2024-01-09.

[1]

[2]

[3]

[4]

[5]