Trial reportThe New England journal of medicine2023
Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated
3 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase IClinical Trial, Phase II
In one paragraph
Trial report in The New England journal of medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 327 papers, 4 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
327citing papers in PubMed, 4 pooled it
44.1field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1
NCT07294261 phase2not yet recruitingnot on this mapstarted 2025, after this paper: background citation
A Multicenter, Prospective Clinical Study Evaluating Goselasib Combination Therapy for First-Line Treatment of KRAS G12C Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Neoadjuvant Treatment of Fulzerasib Plus Cetuximab N01 in KRAS G12C Mutated Locally Advanced Colorectal Cancer With or Without Resectable Metastases
Who cites it
327 citing papers in PubMed, 4 syntheses or guidelines pooled it, 447 citations in OpenAlex.
- Prognostic significance of KRAS G12C versus non-G12C RAS mutations in metastatic colorectal cancer: a systematic review and meta-analysis.The oncologist · 2026Pooled it
- KRAS G12C inhibitors in KRASFrontiers in immunology · 2026Pooled it
- Efficacy and safety of KRAS -G12C inhibitors in colorectal cancer: a systematic review of clinical trials.Medical oncology (Northwood, London, England) · 2025Pooled it
- KEAP1 mutations as key crucial prognostic biomarkers for resistance to KRAS-G12C inhibitors.Journal of translational medicine · 2025Pooled it
- Safety and efficacy of lapatinib, binimetinib, and vinorelbine for RAS mutant metastatic colorectal cancer: results of the RASTRIC Phase I/II trial.British journal of cancer · 2026Trial
- D3S-001 in advanced solid tumors with KRASNature medicine · 2025Trial
- Garsorasib, a KRAS G12C inhibitor, with or without cetuximab, an EGFR antibody, in colorectal cancer cohorts of a phase II trial in advanced solid tumors with KRAS G12C mutation.Signal transduction and targeted therapy · 2025Trial
- Ligand-activated EGFR/MAPK signaling but not PI3K, are key resistance mechanisms to EGFR-therapy in colorectal cancer.Nature communications · 2025Trial
- First-line treatment of anti-EGFR monoclonal antibody cetuximab β plus FOLFIRI versus FOLFIRI alone in Chinese patients with RAS/BRAF wild-type metastatic colorectal cancer: a randomized, phase 3 trial.Signal transduction and targeted therapy · 2025Trial
- Onvansertib in Combination With Chemotherapy and Bevacizumab in Second-Line Treatment ofJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Targeting molecular and genetic pathways driving tumorigenesis for precision therapy in colorectal cancer.Cancer biology & therapy · 2026Review
- RAF1 scaffold integrity shapes chemogenetic degradation outcomes in KRAS-driven lung cancer models.Life science alliance · 2026Article
- Next-generation sequencing using a targeted gene panel in advanced solid tumors: five years of experience from an Italian referral institution.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Oncogenic RAS as an adaptive signaling ecosystem: context-dependent vulnerabilities and resistance-informed therapeutic design.Experimental hematology & oncology · 2026Review
- Resistance Phenotypes and Treatment Sequencing After Immune Checkpoint Blockade in MSI-H/dMMR Metastatic Colorectal Cancer: A Review.Journal of gastrointestinal cancer · 2026Review
- Pancreatic Cancer KRAS Breakthrough: Drug Graveyard No More.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Targeting adaptive EGFR feedback enhances the therapeutic efficacy of RMC-6236 in cholangiocarcinoma.Experimental hematology & oncology · 2026Article
- Review
- External Validation of the ARCAD Nomogram in a Real-World Cohort with Stage 4 Colorectal Cancer.Cancers · 2026Article
- Beyond KRASG12C: emerging therapeutic strategies, patent landscape, and clinical progress in targeting KRAS-mutant cancers.Medical oncology (Northwood, London, England) · 2026Review
267 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
15 authors at 11 institutions in 3 countries.
Rona YaegerFrom the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.Y.); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill (J.W.); Sarah Cannon Research Institute, Tennessee Oncology, Nashville (M.S.P.); Virginia Cancer Specialists, NEXT Oncology-Virginia, Fairfax (A.I.S.); US Oncology Research, the Woodlands (A.I.S.), and Mary Crowley Cancer Research, Dallas (M.B.) - both in Texas; the University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange (S.-H.I.O.), and Mirati Therapeutics, San Diego (J.G.C., K.V., T.K., H.D.-T.) - all in California; the Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta (T.A.L.); Medical Oncology, Mayo Clinic, Phoenix, Arizona (T.S.B.-S.); Belfer Center for Applied Cancer Science and the Department of Medical Oncology, Dana-Farber Cancer Institute (C.P.P., G.A.H.), and the Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital (S.J.K.) - both in Boston.
Jared WeissFrom the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.Y.); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill (J.W.); Sarah Cannon Research Institute, Tennessee Oncology, Nashville (M.S.P.); Virginia Cancer Specialists, NEXT Oncology-Virginia, Fairfax (A.I.S.); US Oncology Research, the Woodlands (A.I.S.), and Mary Crowley Cancer Research, Dallas (M.B.) - both in Texas; the University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange (S.-H.I.O.), and Mirati Therapeutics, San Diego (J.G.C., K.V., T.K., H.D.-T.) - all in California; the Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta (T.A.L.); Medical Oncology, Mayo Clinic, Phoenix, Arizona (T.S.B.-S.); Belfer Center for Applied Cancer Science and the Department of Medical Oncology, Dana-Farber Cancer Institute (C.P.P., G.A.H.), and the Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital (S.J.K.) - both in Boston.
Meredith S PelsterFrom the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.Y.); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill (J.W.); Sarah Cannon Research Institute, Tennessee Oncology, Nashville (M.S.P.); Virginia Cancer Specialists, NEXT Oncology-Virginia, Fairfax (A.I.S.); US Oncology Research, the Woodlands (A.I.S.), and Mary Crowley Cancer Research, Dallas (M.B.) - both in Texas; the University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange (S.-H.I.O.), and Mirati Therapeutics, San Diego (J.G.C., K.V., T.K., H.D.-T.) - all in California; the Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta (T.A.L.); Medical Oncology, Mayo Clinic, Phoenix, Arizona (T.S.B.-S.); Belfer Center for Applied Cancer Science and the Department of Medical Oncology, Dana-Farber Cancer Institute (C.P.P., G.A.H.), and the Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital (S.J.K.) - both in Boston.
Alexander I SpiraFrom the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.Y.); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill (J.W.); Sarah Cannon Research Institute, Tennessee Oncology, Nashville (M.S.P.); Virginia Cancer Specialists, NEXT Oncology-Virginia, Fairfax (A.I.S.); US Oncology Research, the Woodlands (A.I.S.), and Mary Crowley Cancer Research, Dallas (M.B.) - both in Texas; the University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange (S.-H.I.O.), and Mirati Therapeutics, San Diego (J.G.C., K.V., T.K., H.D.-T.) - all in California; the Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta (T.A.L.); Medical Oncology, Mayo Clinic, Phoenix, Arizona (T.S.B.-S.); Belfer Center for Applied Cancer Science and the Department of Medical Oncology, Dana-Farber Cancer Institute (C.P.P., G.A.H.), and the Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital (S.J.K.) - both in Boston.
Minal BarveFrom the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.Y.); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill (J.W.); Sarah Cannon Research Institute, Tennessee Oncology, Nashville (M.S.P.); Virginia Cancer Specialists, NEXT Oncology-Virginia, Fairfax (A.I.S.); US Oncology Research, the Woodlands (A.I.S.), and Mary Crowley Cancer Research, Dallas (M.B.) - both in Texas; the University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange (S.-H.I.O.), and Mirati Therapeutics, San Diego (J.G.C., K.V., T.K., H.D.-T.) - all in California; the Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta (T.A.L.); Medical Oncology, Mayo Clinic, Phoenix, Arizona (T.S.B.-S.); Belfer Center for Applied Cancer Science and the Department of Medical Oncology, Dana-Farber Cancer Institute (C.P.P., G.A.H.), and the Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital (S.J.K.) - both in Boston.
Sai-Hong I OuFrom the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.Y.); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill (J.W.); Sarah Cannon Research Institute, Tennessee Oncology, Nashville (M.S.P.); Virginia Cancer Specialists, NEXT Oncology-Virginia, Fairfax (A.I.S.); US Oncology Research, the Woodlands (A.I.S.), and Mary Crowley Cancer Research, Dallas (M.B.) - both in Texas; the University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange (S.-H.I.O.), and Mirati Therapeutics, San Diego (J.G.C., K.V., T.K., H.D.-T.) - all in California; the Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta (T.A.L.); Medical Oncology, Mayo Clinic, Phoenix, Arizona (T.S.B.-S.); Belfer Center for Applied Cancer Science and the Department of Medical Oncology, Dana-Farber Cancer Institute (C.P.P., G.A.H.), and the Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital (S.J.K.) - both in Boston.
Ticiana A LealFrom the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.Y.); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill (J.W.); Sarah Cannon Research Institute, Tennessee Oncology, Nashville (M.S.P.); Virginia Cancer Specialists, NEXT Oncology-Virginia, Fairfax (A.I.S.); US Oncology Research, the Woodlands (A.I.S.), and Mary Crowley Cancer Research, Dallas (M.B.) - both in Texas; the University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange (S.-H.I.O.), and Mirati Therapeutics, San Diego (J.G.C., K.V., T.K., H.D.-T.) - all in California; the Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta (T.A.L.); Medical Oncology, Mayo Clinic, Phoenix, Arizona (T.S.B.-S.); Belfer Center for Applied Cancer Science and the Department of Medical Oncology, Dana-Farber Cancer Institute (C.P.P., G.A.H.), and the Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital (S.J.K.) - both in Boston.
Tanios S Bekaii-SaabFrom the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.Y.); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill (J.W.); Sarah Cannon Research Institute, Tennessee Oncology, Nashville (M.S.P.); Virginia Cancer Specialists, NEXT Oncology-Virginia, Fairfax (A.I.S.); US Oncology Research, the Woodlands (A.I.S.), and Mary Crowley Cancer Research, Dallas (M.B.) - both in Texas; the University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange (S.-H.I.O.), and Mirati Therapeutics, San Diego (J.G.C., K.V., T.K., H.D.-T.) - all in California; the Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta (T.A.L.); Medical Oncology, Mayo Clinic, Phoenix, Arizona (T.S.B.-S.); Belfer Center for Applied Cancer Science and the Department of Medical Oncology, Dana-Farber Cancer Institute (C.P.P., G.A.H.), and the Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital (S.J.K.) - both in Boston.
Cloud P PaweletzFrom the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.Y.); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill (J.W.); Sarah Cannon Research Institute, Tennessee Oncology, Nashville (M.S.P.); Virginia Cancer Specialists, NEXT Oncology-Virginia, Fairfax (A.I.S.); US Oncology Research, the Woodlands (A.I.S.), and Mary Crowley Cancer Research, Dallas (M.B.) - both in Texas; the University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange (S.-H.I.O.), and Mirati Therapeutics, San Diego (J.G.C., K.V., T.K., H.D.-T.) - all in California; the Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta (T.A.L.); Medical Oncology, Mayo Clinic, Phoenix, Arizona (T.S.B.-S.); Belfer Center for Applied Cancer Science and the Department of Medical Oncology, Dana-Farber Cancer Institute (C.P.P., G.A.H.), and the Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital (S.J.K.) - both in Boston.
Grace A HeaveyFrom the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.Y.); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill (J.W.); Sarah Cannon Research Institute, Tennessee Oncology, Nashville (M.S.P.); Virginia Cancer Specialists, NEXT Oncology-Virginia, Fairfax (A.I.S.); US Oncology Research, the Woodlands (A.I.S.), and Mary Crowley Cancer Research, Dallas (M.B.) - both in Texas; the University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange (S.-H.I.O.), and Mirati Therapeutics, San Diego (J.G.C., K.V., T.K., H.D.-T.) - all in California; the Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta (T.A.L.); Medical Oncology, Mayo Clinic, Phoenix, Arizona (T.S.B.-S.); Belfer Center for Applied Cancer Science and the Department of Medical Oncology, Dana-Farber Cancer Institute (C.P.P., G.A.H.), and the Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital (S.J.K.) - both in Boston.
James G ChristensenFrom the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.Y.); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill (J.W.); Sarah Cannon Research Institute, Tennessee Oncology, Nashville (M.S.P.); Virginia Cancer Specialists, NEXT Oncology-Virginia, Fairfax (A.I.S.); US Oncology Research, the Woodlands (A.I.S.), and Mary Crowley Cancer Research, Dallas (M.B.) - both in Texas; the University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange (S.-H.I.O.), and Mirati Therapeutics, San Diego (J.G.C., K.V., T.K., H.D.-T.) - all in California; the Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta (T.A.L.); Medical Oncology, Mayo Clinic, Phoenix, Arizona (T.S.B.-S.); Belfer Center for Applied Cancer Science and the Department of Medical Oncology, Dana-Farber Cancer Institute (C.P.P., G.A.H.), and the Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital (S.J.K.) - both in Boston.
Karen VelasteguiFrom the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.Y.); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill (J.W.); Sarah Cannon Research Institute, Tennessee Oncology, Nashville (M.S.P.); Virginia Cancer Specialists, NEXT Oncology-Virginia, Fairfax (A.I.S.); US Oncology Research, the Woodlands (A.I.S.), and Mary Crowley Cancer Research, Dallas (M.B.) - both in Texas; the University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange (S.-H.I.O.), and Mirati Therapeutics, San Diego (J.G.C., K.V., T.K., H.D.-T.) - all in California; the Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta (T.A.L.); Medical Oncology, Mayo Clinic, Phoenix, Arizona (T.S.B.-S.); Belfer Center for Applied Cancer Science and the Department of Medical Oncology, Dana-Farber Cancer Institute (C.P.P., G.A.H.), and the Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital (S.J.K.) - both in Boston.
Thian KheohFrom the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.Y.); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill (J.W.); Sarah Cannon Research Institute, Tennessee Oncology, Nashville (M.S.P.); Virginia Cancer Specialists, NEXT Oncology-Virginia, Fairfax (A.I.S.); US Oncology Research, the Woodlands (A.I.S.), and Mary Crowley Cancer Research, Dallas (M.B.) - both in Texas; the University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange (S.-H.I.O.), and Mirati Therapeutics, San Diego (J.G.C., K.V., T.K., H.D.-T.) - all in California; the Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta (T.A.L.); Medical Oncology, Mayo Clinic, Phoenix, Arizona (T.S.B.-S.); Belfer Center for Applied Cancer Science and the Department of Medical Oncology, Dana-Farber Cancer Institute (C.P.P., G.A.H.), and the Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital (S.J.K.) - both in Boston.
Hirak Der-TorossianFrom the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.Y.); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill (J.W.); Sarah Cannon Research Institute, Tennessee Oncology, Nashville (M.S.P.); Virginia Cancer Specialists, NEXT Oncology-Virginia, Fairfax (A.I.S.); US Oncology Research, the Woodlands (A.I.S.), and Mary Crowley Cancer Research, Dallas (M.B.) - both in Texas; the University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange (S.-H.I.O.), and Mirati Therapeutics, San Diego (J.G.C., K.V., T.K., H.D.-T.) - all in California; the Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta (T.A.L.); Medical Oncology, Mayo Clinic, Phoenix, Arizona (T.S.B.-S.); Belfer Center for Applied Cancer Science and the Department of Medical Oncology, Dana-Farber Cancer Institute (C.P.P., G.A.H.), and the Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital (S.J.K.) - both in Boston.
Samuel J KlempnerFrom the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.Y.); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill (J.W.); Sarah Cannon Research Institute, Tennessee Oncology, Nashville (M.S.P.); Virginia Cancer Specialists, NEXT Oncology-Virginia, Fairfax (A.I.S.); US Oncology Research, the Woodlands (A.I.S.), and Mary Crowley Cancer Research, Dallas (M.B.) - both in Texas; the University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange (S.-H.I.O.), and Mirati Therapeutics, San Diego (J.G.C., K.V., T.K., H.D.-T.) - all in California; the Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta (T.A.L.); Medical Oncology, Mayo Clinic, Phoenix, Arizona (T.S.B.-S.); Belfer Center for Applied Cancer Science and the Department of Medical Oncology, Dana-Farber Cancer Institute (C.P.P., G.A.H.), and the Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital (S.J.K.) - both in Boston.ORCID 0000-0002-4062-0808
Mirati Therapeutics (United States) · USDana-Farber Cancer Institute · USEmory University · USMary Crowley Cancer Research Center · USMassachusetts General Hospital · USMayo Clinic Hospital · USMemorial Sloan Kettering Cancer Center · USSarah Cannon · USUniversity of California, Irvine · USUniversity of North Carolina at Chapel Hill · USVirginia Cancer Specialists · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MWomen's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3MNCI NIH HHS P30 CA008748NCI NIH HHS P30 CA015083
Abstract
backgroundAdagrasib, an oral small-molecule inhibitor of mutant KRAS G12C protein, has shown clinical activity in pretreated patients with several tumor types, including colorectal cancer. Preclinical studies suggest that combining a KRAS G12C inhibitor with an epidermal growth factor receptor antibody could be an effective clinical strategy.
methodsIn this phase 1-2, open-label, nonrandomized clinical trial, we assigned heavily pretreated patients with metastatic colorectal cancer with mutant KRAS G12C to receive adagrasib monotherapy (600 mg orally twice daily) or adagrasib (at the same dose) in combination with intravenous cetuximab once a week (with an initial loading dose of 400 mg per square meter of body-surface area, followed by a dose of 250 mg per square meter) or every 2 weeks (with a dose of 500 mg per square meter). The primary end points were objective response (complete or partial response) and safety.
resultsAs of June 16, 2022, a total of 44 patients had received adagrasib, and 32 had received combination therapy with adagrasib and cetuximab, with a median follow-up of 20.1 months and 17.5 months, respectively. In the monotherapy group (43 evaluable patients), a response was reported in 19% of the patients (95% confidence interval [CI], 8 to 33). The median response duration was 4.3 months (95% CI, 2.3 to 8.3), and the median progression-free survival was 5.6 months (95% CI, 4.1 to 8.3). In the combination-therapy group (28 evaluable patients), the response was 46% (95% CI, 28 to 66). The median response duration was 7.6 months (95% CI, 5.7 to not estimable), and the median progression-free survival was 6.9 months (95% CI, 5.4 to 8.1). The percentage of grade 3 or 4 treatment-related adverse events was 34% in the monotherapy group and 16% in the combination-therapy group. No grade 5 adverse events were observed.
conclusionsAdagrasib had antitumor activity in heavily pretreated patients with metastatic colorectal cancer with mutant KRAS G12C, both as oral monotherapy and in combination with cetuximab. The median response duration was more than 6 months in the combination-therapy group. Reversible adverse events were common in the two groups. (Funded by Mirati Therapeutics; KRYSTAL-1 ClinicalTrials.gov number, NCT03785249.).
Indexed as
Antineoplastic AgentsCetuximabColorectal NeoplasmsAcetonitrilesAntineoplastic Combined Chemotherapy ProtocolsHumansPiperazinesProto-Oncogene Proteins p21(ras)PyrimidinesAcetonitrilesadagrasibAntineoplastic AgentsCetuximabKRAS protein, humanPiperazinesProto-Oncogene Proteins p21(ras)Pyrimidines
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.