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Our RAS(ON) inhibitor clinical trials are intended to evaluate safety and efficacy in patients with RAS mutant cancers with unmet medical need

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Revolution Medicines’ Clinical Trial Program Is Evaluating Investigational Treatments for RAS Mutant Cancers

Our novel RAS(ON) inhibitors are under investigation for treating different types of RAS mutant cancers, including pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and other solid tumors

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Revolution Medicines’ RAS(ON) Inhibitor Clinical Trials Program

Daraxonrasib

RASolute 302
(Phase 3)

Previously treated metastatic PDAC

RASolute 304
(Phase 3)

Resected PDAC

RASolve 301
(Phase 3)

Previously treated, locally advanced or metastatic RAS mutant NSCLC

RMC-6236-001
(Phase 1/2)

Treatment naïve or previously treated advanced solid tumors haboring specific mutations in RAS

Elironrasib

RMC-6291-001
(Phase 1/1b)

Locally advanced or metastatic KRAS G12C mutant solid tumors

Zoldonrasib

RMC-9805-001
(Phase 1/1b)

Previously treated, locally advanced or metastatic KRAS G12D mutant solid tumors

RAS(ON) inhibitor combinations

RMC-GI-102
(Phase 1/2)

Previously treated and treatment-naïve solid tumors, particularly gastrointestinal tumors

RMC-LUNG-101
(Phase 1b/2)

Locally advanced or metastatic NSCLC or other advanced solid tumors

RMC-6291-101
(Phase 1b)

Previously treated advanced or metastatic KRAS G12C mutant solid tumors

The safety and efficacy of the agents and/or uses under investigation have not been established

aThis is not a complete list of eligibility criteria; for more information, please go to ClinicalTrials.gov. bThese criteria are for specific subprotocols within the clinical trial. Refer to the ClinicalTrials.gov record for more information.

RAS Protein Biology and RAS Mutant Cancers

RAS Proteins Play a Key Regulatory Role in Cell Growth and Development

This visual is for illustrative purposes only and does not represent all molecular components
of the RAS pathway.

RAS Mutations Are Common Across Multiple Tumor Types and Are Associated With Poor Survival Outcomes

RAS mutations

  • RAS mutations are present in approximately one-fifth of human cancers
  • In the presence of oncogenic mutations, such as G12X,a G13X,a and Q61X,a RAS proteins (i.e., KRAS, HRAS, or NRAS) are predominantly ON, which can drive cancer initiation and progression

RAS mutations in cancers

  • Cancers commonly driven by RAS mutations include PDAC (~92% RAS mutant), CRC (~50% RAS mutant), and NSCLC (~30% RAS mutant), all of which exhibit a wide array of RAS variants
  • Inhibiting RAS signaling could impede tumor growth, but there are limited therapeutic options that directly inhibit RAS

This visual is for illustrative purposes only and represents a high-level depiction of select RAS mutations.a

a“X” denotes any amino acid residue point mutation in a given codon (i.e., G12C, G12D, G12V, G13D, Q61H).

Please click on the pancreas, colon, or lungs to learn more about each disease state

The Tri-Complex Inhibitor Platform

RAS(ON) Tri-Complex Inhibitors Are Designed to Block RAS(ON) Activity

Click on the different components to see how RAS(ON) tri-complex inhibitors work

Revolution Medicines’ novel tri-complex inhibitor platform is intended to block RAS in its ON state
and reduce downstream oncogenic signaling

Investigational RAS(ON) Inhibitors

Three Investigational Revolution Medicines RAS(ON) Inhibitors Are in Clinical-Stage Trials for Treating RAS Mutant Cancers

Daraxonrasib (RMC-6236)

A RAS(ON) multi-selective
noncovalent inhibitor

Ongoing clinical trials in PDAC and NSCLC

Current Phase 3 or early phase clinical trials include RASolute 302, RASolve 301, and RMC‑6236‑001

Zoldonrasib (RMC-9805)

A RAS(ON) G12D-selective
covalent inhibitor

Ongoing clinical trials in advanced solid tumors

Current early phase clinical trials include RMC‑LUNG‑101, RMC‑9805‑001, and RMC‑GI‑102

Elironrasib (RMC-6291)

A RAS(ON) G12C-selective
covalent inhibitor

Ongoing clinical trials in advanced solid tumors

Current early phase clinical trials include RMC‑LUNG‑101, RMC‑6291‑101, and RMC‑6291‑001

Click here for more information about Revolution Medicines’ RAS(ON) inhibitor pipeline

Abbreviations

ACS, American Cancer Society; AKT, protein kinase B; CNS, central nervous system; CRC, colorectal cancer; CYPA, cyclophilin A; ERK, extracellular signal-regulated kinase; GAP, GTPase-activating protein; GDP, guanine diphosphate; GEF, guanine nucleotide exchange factor; GTP, guanine triphosphate; HRAS, Harvey rat sarcoma viral oncogene homolog; KRAS, Kirsten rat sarcoma; MEK, mitogen-activated protein kinase kinase; mTOR, mammalian target of rapamycin; NCI/SEER, National Cancer Institute/Surveillance, Epidemiology, and End Results; NRAS, neuroblastoma RAS viral oncogene homolog; NSCLC, non-small cell lung cancer; PDAC, pancreatic ductal adenocarcinoma; PI3K, phosphatidylinositol-4,5-bisphosphate 3-kinase; RAF, rapidly accelerated fibrosarcoma; RAS, rat sarcoma.

References

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