Trial reportScience (New York, N.Y.)2017
Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade.
16 registry-linked trialsAbstract readClinical Trial, Phase II
In one paragraph
Trial report in Science (New York, N.Y.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 16 registered trials, which are not on this map. Cited by 4,016 papers, 6 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
4,016citing papers in PubMed, 6 pooled it
–field-weighted citation impact
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.
Phase 2 Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors
NIVOLUMAB Plus IPILIMUMAB and TEMOZOLOMIDE in Combination in Microsatellite Stable (MSS), MGMT Silenced Metastatic Colorectal Cancer (mCRC): the MAYA Study
Lenvatinib Combined Pembrolizumab as a Second-line Treatment in Advanced Hepatobiliary Tumors: a Single-center, Single-arm, Non-randomized Clinical Study
Pembrolizumab With Axitinib in Recurrent Endometrial Cancer With Deficient Mismatch Repair System Post PD1 Exposure: Phase II Trial
Advanced Immune Gene and Cell Therapies for Liver Metastases
A Single Arm, Open Label, Phase II, Exploratory Study of Fruquitinib Combined With Camrelizumab in Non MSI-H / dMMR Refractory Colorectal Cancer.
StrataPATH™ (Precision Indications for Approved Therapies): A Study Evaluating the Clinical Activity and Safety of Approved Drugs Within Biomarker-Guided Patients With Solid Tumors
Melanoma: Genomic Profiles, Molecular Markers and Therapeutic Implications
A Study on Serum Exosomal miRNA Predicting the Effective and Prognosis of Immunotherapy Combined With Chemotherapy in Pulmonary Squamous Carcinoma
Combination of Regorafenib，Toripalimab and Celecoxib in Mismatch Repair (MMR) Proficient Refractory Advanced Colorectal Cancer Without Liver Metastasis：a Single Arm Phase II REGOTORICOX Study.
Multi-center, Non-interventional, Prospective Registry Study on the Treatment of Solid Tumors With Mismatch Repair Deficiency or Microsatellite Instability
Study on the Clinical Potential of Circulating Tumor DNA in Advanced or Locally Advanced dMMR/MSI-H Colorectal Patients Treated With Immunotherapy
A Single-arm, Exploratory Phase II Clinical Trial of Combined Radiotherapy and HAIC as First-line Treatment for Unresectable Locally Advanced Distal Cholangiocarcinoma
HDAC Inhibitor Combination With Immunochemotherapy in the Neoadjuvant Treatment of pMMR Locally Advanced Colon Cancer: A Multicenter, Double-arm, Phase II Randomized Controlled Study
A Single-Arm, Phase II Study Evaluating Combination Balstilimab Plus Botensilimab With AgenT-797 in Previously Treated Patients With pMMR Metastatic CRC With Liver Metastases
Correlation Analysis of Gene Characteristics of Malignant Tumors With Prognosis
Who cites it
4,016 citing papers in PubMed, 6 syntheses or guidelines pooled it.
- Baseline D-dimer as a predictor of immune checkpoint inhibitor efficacy in cancer.Annals of medicine · 2026Pooled it
- Neoadjuvant Immunotherapy in Localized dMMR/MSI-H Colon Cancer: A Systematic Review of Pathological Response and Surgical Outcomes.Annals of surgical oncology · 2026Pooled it
- First-Line Immunotherapy Versus Chemotherapy in MSI-H/dMMR Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis of Phase III Studies.Journal of gastrointestinal cancer · 2026Pooled it
- Pooled it
- Perioperative Immunotherapy for Pancreatic Cancer: A Systematic Review of Randomized Controlled Trials.Journal of gastrointestinal cancer · 2026Pooled it
- Neoadjuvant immune checkpoint inhibitors for localized dMMR/MSI-H gastric cancer: a meta-analysis.ESMO open · 2026Pooled it
- Pembrolizumab combined with disitamab vedotin in human epidermal growth factor receptor 2-positive metastatic colorectal cancer.The oncologist · 2026Trial
- Motixafortide, cemiplimab, gemcitabine and nab-paclitaxel in metastatic pancreatic cancer: a single-arm phase 2 study with single-cell correlatives.Nature communications · 2026Trial
- Durable responses to triplet immunotherapy targeting TGF-β, PD-L1, and tumor antigen, with an IL-15 receptor superagonist in mismatch repair proficient castration-resistant prostate cancer.Journal for immunotherapy of cancer · 2026Trial
- Copanlisib in combination with nivolumab formicrosatellite stable colorectal cancer: a phase 1/2 trial.Nature communications · 2026Trial
- Biomarker study of pembrolizumab in patients with advanced rare cancers.Cell reports. Medicine · 2026Trial
- Pembrolizumab and olaparib in homologous-recombination-deficient metastatic pancreatic cancer: the phase 2 POLAR trial.Nature medicine · 2026Trial
- Toripalimab in patients with previously treated advanced upper tract urothelial carcinoma: a subgroup analysis of the phase II POLARIS-03 trial.The oncologist · 2026Trial
- xinguangA preliminary characterization of PI4K/PIPK alterations across solid tumors: an exploratory framework for prognostic and therapeutic stratification.Cancer biology & therapy · 2026Article
- Beyond variant detection: Mismatch repair gene alterations in plasma cell-free DNA from 1,226 glioma samples, and plasma-confirmed functional deficiency in an unbiopsied pontine glioma.The journal of liquid biopsy · 2026Article
- Body mass index and dyslipidemia influence responses to anti-PD-1 immunotherapy in colorectal cancer.Annals of medicine · 2026Article
- Clinico-molecular characteristics and enhanced efficacy of immune checkpoint inhibitors in TP53-mutated advanced biliary tract cancer.Journal of gastroenterology · 2026Article
- Research progress of aptamers in the diagnosis and treatment of colorectal cancer (Review).Molecular medicine reports · 2026Review
- The Immune Checkpoint Inhibitors Journey: From Early Promise to Lasting Impact.Journal of immunotherapy and precision oncology · 2026Review
- Molecular predictors of minimal residual disease in newly diagnosed multiple myeloma treated with quadruplet therapy.Nature medicine · 2026Article
3,956 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
46 authors.
Dung T LeBloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.ORCID 0000-0002-2110-7697
Jennifer N DurhamBloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.ORCID 0000-0001-9097-9125
Kellie N SmithBloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.ORCID 0000-0002-6295-8930
Hao WangSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
Bjarne R BartlettSwim Across America Laboratory at Johns Hopkins, Baltimore, MD 21287, USA.ORCID 0000-0001-8579-0379
Laveet K AulakhSwim Across America Laboratory at Johns Hopkins, Baltimore, MD 21287, USA.
Steve LuSwim Across America Laboratory at Johns Hopkins, Baltimore, MD 21287, USA.ORCID 0000-0002-8201-8583
Holly KemberlingSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.ORCID 0000-0002-2997-324X
Cara WiltSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.ORCID 0000-0002-4054-7452
Brandon S LuberSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
Fay WongSwim Across America Laboratory at Johns Hopkins, Baltimore, MD 21287, USA.ORCID 0000-0001-9759-3778
Nilofer S AzadBloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.
Agnieszka A RuckiBloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.
Dan LaheruSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
Ross DonehowerSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
Atif ZaheerDepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.ORCID 0000-0002-4824-6654
George A FisherDepartment of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Todd S CrocenziProvidence Cancer Center at Providence Health & Services, Portland, OR 97213, USA.ORCID 0000-0001-8762-1990
James J LeeDepartment of Medicine, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA.ORCID 0000-0001-6749-9350
Tim F GretenGastrointestinal Malignancies Section, Thoracic-GI Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.ORCID 0000-0002-0806-2535
Austin G DuffyGastrointestinal Malignancies Section, Thoracic-GI Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.ORCID 0000-0001-9277-0157
Kristen K CiomborDivision of Medical Oncology, Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.ORCID 0000-0002-8992-9515
Aleksandra D EyringMerck & Co. Inc., Kenilworth, NJ 07033, USA.
Bao H LamMerck & Co. Inc., Kenilworth, NJ 07033, USA.
Andrew JoeMerck & Co. Inc., Kenilworth, NJ 07033, USA.
S Peter KangMerck & Co. Inc., Kenilworth, NJ 07033, USA.
Matthias HoldhoffSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
Ludmila DanilovaBloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.ORCID 0000-0003-2813-3094
Leslie CopeBloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.ORCID 0000-0002-4098-3289
Christian MeyerSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.ORCID 0000-0003-3329-7106
Shibin ZhouBloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.ORCID 0000-0003-1941-4425
Richard M GoldbergWest Virginia University Cancer Institute, Morgantown, WV 26506, USA.ORCID 0000-0003-0308-8223
Deborah K ArmstrongSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
Katherine M BeverSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.ORCID 0000-0001-5230-4661
Amanda N FaderDepartment of Gynecology and Obstetrics, Johns Hopkins Medicine, Baltimore, MD 21287, USA.
Janis TaubeBloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.
Franck HousseauBloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.
David SpetzlerCaris Life Sciences, Phoenix, AZ 85040, USA.
Nianqing XiaoCaris Life Sciences, Phoenix, AZ 85040, USA.ORCID 0000-0001-9388-5028
Drew M PardollBloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.
Nickolas PapadopoulosSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
Kenneth W KinzlerSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
James R EshlemanDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.ORCID 0000-0002-9274-8459
Bert VogelsteinBloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.ORCID 0000-0003-0766-3854
Robert A AndersBloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.
Luis A DiazBloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA. ldiaz@mskcc.org.ORCID 0000-0002-7079-8914
Funding
Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6MTranslational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Tasleem J Padamsee · 1985 to 2026
$132.3MTumor Antigens for Individual Signatures and TherapyP50CA062924 · NCI · JOHNS HOPKINS UNIVERSITY · PI LENNON, ANNE MARIE · 1993 to 2022
$54.6MTreatment of HIV- and HIV+ Patients with HPV16+ CIN2/3 Using pNGLV4a-hCRTE6E7L2 DNA vaccine administered intramuscularly via electroporationP50CA098252 · NCI · JOHNS HOPKINS UNIVERSITY · PI Richard Bruce Roden · 2003 to 2026
$53.5MMEDICAL SCIENTIST TRAINING PROGRAMT32GM007309 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI COX, ANDREA L · 1985 to 2019
$43.2MVanderbilt Clinical Oncology Research Career Development ProgramK12CA090625 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Debra L. Friedman, Paula Jill Hurley · 2001 to 2026
$16.9MMOLECULAR GENETIC ANALYSIS OF COLORECTAL CANCERR37CA043460 · NCI · JOHNS HOPKINS UNIVERSITY · PI VOGELSTEIN, BERT · 1997 to 2016
$7.4MGenes from the FAP LocusR37CA057345 · NCI · JOHNS HOPKINS UNIVERSITY · PI KINZLER, KENNETH W. · 2002 to 2016
$7.4MClinical protocols for the treatment of GI cancerZIABC011343 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GRETEN, TIM · 2010 to 2025
$4.8MINCIDENCE AND MOLECULAR SCREENING FOR HEREDITARY CANCERR01CA067941 · NCI · OHIO STATE UNIVERSITY · PI DE LA CHAPELLE, ALBERT · 2000 to 2004
$2.9MCorrelates of antitumor immunity in colorectal cancers and anti PD1 therapyR01CA203891 · NCI · JOHNS HOPKINS UNIVERSITY · PI HOUSSEAU, FRANCK · 2016 to 2020
$1.9MGENES FROM THE FAP LOCUSR01CA057345 · NCI · JOHNS HOPKINS UNIVERSITY · PI KINZLER, KENNETH W. · 1992 to 2001
$734kHoward Hughes Medical InstituteNCI NIH HHS K12 CA090625NCI NIH HHS K23 CA163672NCI NIH HHS P30 CA006973NCI NIH HHS P30 CA016058NCI NIH HHS P50 CA062924NCI NIH HHS P50 CA098252NCI NIH HHS R01 CA057345NCI NIH HHS R01 CA067941NCI NIH HHS R01 CA203891NCI NIH HHS R37 CA043460NCI NIH HHS R37 CA057345NCI NIH HHS U01 CA067941NIGMS NIH HHS T32 GM007309
Abstract
The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor-1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair-deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached. Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor. These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair-deficient cancers make them sensitive to immune checkpoint blockade, regardless of the cancers' tissue of origin.
Indexed as
AdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntigens, NeoplasmBiomarkers, TumorBrain NeoplasmsCell Cycle CheckpointsColorectal NeoplasmsDisease-Free SurvivalDNA Mismatch RepairFemaleHumansMaleMiddle AgedMutationAntibodies, Monoclonal, HumanizedAntigens, NeoplasmBiomarkers, TumorPDCD1 protein, humanpembrolizumabProgrammed Cell Death 1 Receptor
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NCT01876511ClinicalTrials.gov
NCT03832621ClinicalTrials.gov
NCT03895970ClinicalTrials.gov
NCT04197219ClinicalTrials.gov
NCT04622423ClinicalTrials.gov
NCT04866862ClinicalTrials.gov
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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.