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NOW APPROVED

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A ship breaks through icebergs that reflect the many challenges in treating mPDAC and targeting RAS.

RASONQUE mechanism of action

RASONQUE is a RAS(ON) multi-selective inhibitor that targets the key driver of oncogenesis in metastatic pancreatic adenocarcinoma with a novel inhibitory tri-complex approach.1-3

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RASONQUE is the first and only approved RAS(ON) multi-selective inhibitor1*

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See the novel inhibitory tri-complex in action.
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In pancreatic cancer cells, RAS(ON) is the dominant oncogenic driver, making it an ideal therapeutic target2,3
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  • Preclinical studies demonstrated that RASONQUE can bind to both wild-type† and mutant RAS(ON) proteins1‡
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RASONQUE drives the formation of a novel inhibitory tri-complex with a chaperone protein and RAS(ON)1,4
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PINCH & ZOOM
The tri-complex blocks downstream signaling proteins from binding to RAS(ON), inhibiting downstream growth and survival signaling, ultimately resulting in tumor cell death.
The tri-complex blocks downstream signaling proteins from binding to RAS(ON), inhibiting downstream growth and survival signaling, ultimately resulting in tumor cell death.
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RASONQUE is a first-in-class treatment designed to target all forms of RAS(ON)1
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*RASONQUE is an inhibitor of the RAS GTPase family. RASONQUE binds to cyclophilin A, resulting in a binary complex that binds to the active, GTP-bound state of RAS.1

†Wild-type RAS may also play a role in oncogenesis, as many cases of PDAC with wild-type RAS have alterations in other members of the RAS-MAPK pathway.2

‡Binds RAS(ON) across wild-type and mutant variants, including those with mutations at positions G12, G13, and Q61 in KRAS, NRAS, and HRAS.1,2

§Preclinical studies demonstrated that inhibiting oncogenic RAS signaling with RASONQUE induces tumor cell death.1

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RAS(ON) is the key oncogenic driver of pancreatic adenocarcinoma2

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See how RAS signaling plays a part in oncogenesis.
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RAS proteins function as tightly regulated molecular switches that cycle between the inactive RAS(OFF) state and the active RAS(ON) state5-8
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In normal cells: tightly regulated RAS(ON) proteins control cell growth. In cancer cells, excessive RAS(ON) signaling promotes cell growth.
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In normal cells, RAS proteins primarily remain in the RAS(OFF) state.9
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RAS is transiently switched into the RAS(ON) state in response to growth signals before returning to the RAS(OFF) state.6,8,9
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RAS plays an integral role in regulating cell proliferation and survival5,6
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RAS mutations lead to an accumulation of RAS(ON) proteins, causing excessive RAS(ON) signaling3,5,6,8-11
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In normal cells: tightly regulated RAS(ON) proteins control cell growth. In cancer cells, excessive RAS(ON) signaling promotes cell growth.
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  • RAS(ON) activates cell signaling pathways, such as MAPK and PI3K, that promote cell growth, survival, and proliferation5,7,12
  • Excessive RAS(ON) signaling can cause uncontrolled cell proliferation and survival, which can drive cancer initiation and progression3,10,11
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RAS mutations can drive cancer initiation, progression, and survival3,10,11
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Unmet need in PDAC
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Trial design
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CYPA=cyclophilin A; HRAS=Harvey rat sarcoma; KRAS=Kirsten rat sarcoma; MAPK=mitogen-activated protein kinase; MOA=mechanism of action; NRAS=neuroblastoma rat sarcoma; PDAC=pancreatic adenocarcinoma; PI3K=phosphatidylinositol-4,5-bisphosphate 3-kinase; RAS=rat sarcoma.
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References: 1. RASONQUE. Prescribing information. Revolution Medicines, Inc.; 2026. 2. O’Reilly EM, Wainberg ZA, Hendifar AE, et al; RASolute 302 Trial Investigators. Daraxonrasib or chemotherapy in previously treated metastatic pancreatic cancer. N Engl J Med. Published online May 31, 2026. doi:10.1056/NEJMoa2605555 3. Jiang J, Jiang L, Maldonato BJ, et al. Translational and therapeutic evaluation of RAS-GTP inhibition by RMC-6236 in RAS-driven cancers. Cancer Discov. 2024;14(6):OF1-OF24. doi:10.1158/2159-8290.CD-24-0027 4. Wolpin BM, Wainberg ZA, Hendifar AE, et al; RASolute 302 investigators. Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated metastatic pancreatic adenocarcinoma (mPDAC): primary and final analysis from the phase 3 RASolute 302 study. Presented at: ASCO Annual Meeting; May 29-June 2, 2026; Chicago, IL. 5. Singhal A, Li BT, O’Reilly EM. Targeting KRAS in cancer. Nat Med. 2024;30(4):969-983. doi:10.1038/s41591-024-02903-0 6. Prior IA, Hood FE, Hartley JL. The frequency of Ras mutations in cancer. Cancer Res. 2020;80(14):2969-2974. doi:10.1158/0008-5472.CAN-19-3682 7. Moore AR, Rosenberg SC, McCormick F, Malek S. RAS-targeted therapies: is the undruggable drugged? Nat Rev Drug Discov. 2020;19(8):533-552. doi: 10.1038/s41573-020-0068-6 8. Zhou Y, Hancock JF. Ras nanoclusters: versatile lipid-based signaling platforms. Biochim Biophys Acta. 2015;1853(4):841-849. doi:10.1016/j.bbamcr.2014.09.008 9. Waters AM, Der CJ. KRAS: the critical driver and therapeutic target for pancreatic cancer. Cold Spring Harb Perspect Med. 2018;8(9):a031435. doi:10.1101/cshperspect.a031435 10. Bahar ME, Kim HJ, Kim DR. Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies. Signal Transduct Target Ther. 2023;8(1):455. doi:10.1038/s41392-023-01705-z 11. Cregg J, Edwards AV, Chang S, et al. Discovery of daraxonrasib (RMC-6236), a potent and orally bioavailable RAS(ON) multi-selective, noncovalent tri-complex inhibitor for the treatment of patients with multiple RAS-addicted cancers. J Med Chem. 2025;68(6):6064-6083. doi:10.1021/acs.jmedchem.4c02314 12. Oya Y, Imaizumi K, Mitsudomi T. The next-generation KRAS inhibitors...what comes after sotorasib and adagrasib? Lung Cancer. 2024;194(107886). doi:10.1016/j.lungcan.2024.107886
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