{
  "abstract": "Introduction: Pancreatic ductal adenocarcinoma (PDAC) is associated with a poor prognosis, and RAS gene mutations are present in more than 90% of cases. For this reason, direct RAS inhibition is a promising, but thus far difficult to achieve, therapeutic strategy. Daraxonrasib (RMC-6236) is a first-in-class, oral, non-covalent, multiselective inhibitor of the active form of RAS. It forms an intracellular trimeric complex with cyclophilin A, blocking both mutant and wild-type variants of the KRAS, NRAS, and HRAS genes. The aim of this systematic review was to evaluate the efficacy and safety of daraxonrasib in previously treated patients with RAS-mutated PDAC. Methods: This review was conducted in accordance with the PRISMA 2020 guidelines. A systematic search was conducted in PubMed, Web of Science, and ClinicalTrials.gov for studies published between January 2020 and July 2026. Two studies met the inclusion criteria and were analyzed: the Phase 1-2 RMC-6236-001 (n = 168) and the Phase 3 RASolute 302 trial (n = 500), involving a total of 668 patients. The risk of bias was assessed using the Cochrane RoB 2.0 tool for the randomized trial and the Methodological Index for Non-Randomized Studies (MINORS) tool. Results: In the RASolute 302 trial, daraxonrasib out performed investigator-selected chemotherapy in a population of patients with the RAS G12 mutation, improving median overall survival (13.2 vs. 6.6 months; HR 0.40), progression-free survival (7.3 vs. 3.5 months; HR 0.45), and objective response rate (33.2% vs. 11.8%; all p < 0.001), and also delayed the onset of pain and deterioration in quality of life. These results were consistent with the earlier RMC-6236-001 study (objective response rate [ORR] 35%, median overall survival [OS] 13.1 months in patients with RAS G12 mutation treated in the second-line setting). Daraxonrasib exhibited a predictable toxicity profile, consisting mainly of Grade 1-2 dermatologic and gastrointestinal symptoms, with lower rates of hematologic toxicity and treatment discontinuation than with chemotherapy. Conclusions: Daraxonrasib demonstrates clinically relevant and statistically significant efficacy with an acceptable safety profile in previously treated patients with metastatic RAS G12-mutated PDAC, the population for which the strongest randomized evidence is currently available. These findings support its potential as a promising new treatment option in this setting. Further studies are needed regarding rare RAS gene variants and forms of the disease with wild-type RAS.",
  "abstract_shown": true,
  "affiliations": [
    "Student Scientific Society, Department of Clinical Oncology and Chemotherapy, Medical University of Lublin, 20-059 Lublin, Poland.",
    "Department of Clinical Oncology and Chemotherapy, Medical University of Lublin, 20-059 Lublin, Poland."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Natalia Gierulska",
      "orcid": "0009-0005-8136-9997"
    },
    {
      "affs": [
        0
      ],
      "name": "Nina Jankowska"
    },
    {
      "affs": [
        0
      ],
      "name": "Zuzanna Dąbrowska",
      "orcid": "0009-0000-6632-4938"
    },
    {
      "affs": [
        0
      ],
      "name": "Julia Piekarz",
      "orcid": "0009-0007-2211-1413"
    },
    {
      "affs": [
        1
      ],
      "name": "Magdalena Skórzewska"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/82z1gkhy4f4mz.bib",
  "cited_by": 0,
  "doi": "10.3390/cancers18193112",
  "fulltext_url": "https://europepmc.org/articles/PMC13664388",
  "id": "82z1gkhy4f4mz",
  "issns": [
    "2072-6694"
  ],
  "landing_url": "https://europepmc.org/article/MED/42882807",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|Pancreatic and Hepatic Oncology Research"
    ]
  ],
  "openalex": "W7214380417",
  "pdf_url": "https://europepmc.org/articles/PMC13664388?pdf=render",
  "pmcid": "PMC13664388",
  "pmid": "42882807",
  "published": "2026-09-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/82z1gkhy4f4mz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:16Z",
      "native_id": "MED:42882807",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42882807"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Pancreatic and Hepatic Oncology Research",
      "subfield": "oncology"
    }
  ],
  "title": "Efficacy and Safety of Daraxonrasib (RMC-6236) in Previously Treated Metastatic RAS-Mutated Pancreatic Ductal Adenocarcinoma: A Systematic Review.",
  "title_text": "Efficacy and Safety of Daraxonrasib (RMC-6236) in Previously Treated Metastatic RAS-Mutated Pancreatic Ductal Adenocarcinoma: A Systematic Review.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:16Z",
  "url": "https://research.draconitic.com/paper/82z1gkhy4f4mz",
  "venue": "Cancers",
  "versions": []
}