Trial reportJournal of translational medicine2011
A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma.
Trial report in Journal of translational medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 280 papers, 11 of them syntheses that pooled it.
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.
An Exploratory Study to Determine Potential Predictive Markers of Response and/or Toxicity in Patients With Unresectable Stage III or IV Malignant Melanoma Randomized and Treated With Ipilimumab (MDX-010/BMS-734016) at Two Dose Levels
Predictive Biomarkers For Response To Nivolumab In Head and Neck Squamous Cell Carcinoma
Who cites it
280 citing papers in PubMed, 11 syntheses or guidelines pooled it, 531 citations in OpenAlex.
- Pooled it
- Ipilimumab-Induced Enterocolitis: A Systematic Review and Meta-Analysis.Drug safety · 2020Pooled it
- Meta-analysis of immune-related adverse events of immune checkpoint inhibitor therapy in cancer patients.Thoracic cancer · 2020Pooled it
- Dawn of Monitoring Regulatory T Cells in (Pre-)clinical Studies: Their Relevance Is Slowly Recognised.Frontiers in medicine · 2020Pooled it
- Comparative Risks of High-Grade Adverse Events Among FDA-Approved Systemic Therapies in Advanced Melanoma: Systematic Review and Network Meta-Analysis.Frontiers in oncology · 2020Pooled it
- Potential Immune-Related Adverse Events Associated With Monotherapy and Combination Therapy of Ipilimumab, Nivolumab, and Pembrolizumab for Advanced Melanoma: A Systematic Review and Meta-Analysis.Frontiers in oncology · 2020Pooled it
- Biomarkers, measured during therapy, for response of melanoma patients to immune checkpoint inhibitors: a systematic review.Melanoma research · 2019Pooled it
- Comparative safety of immune checkpoint inhibitors in cancer: systematic review and network meta-analysis.BMJ (Clinical research ed.) · 2018Pooled it
- Evaluation of classical clinical endpoints as surrogates for overall survival in patients treated with immune checkpoint blockers: a systematic review and meta-analysis.Journal of cancer research and clinical oncology · 2018Pooled it
- Pooled it
- Early analysis of surrogate endpoints for metastatic melanoma in immune checkpoint inhibitor trials.Medicine · 2016Pooled it
- Phase 2 study of pembrolizumab in patients with advanced rare cancers.Journal for immunotherapy of cancer · 2020Trial
- An interim report on the investigator-initiated phase 2 study of pembrolizumab immunological response evaluation (INSPIRE).Journal for immunotherapy of cancer · 2019Trial
- Phase II study of the immune-checkpoint inhibitor ipilimumab plus dacarbazine in Japanese patients with previously untreated, unresectable or metastatic melanoma.Cancer chemotherapy and pharmacology · 2015Trial
- The Real-World Safety Profile of Immune Checkpoint Inhibitors in Melanoma: FAERS Pharmacovigilance Analysis Complemented by Randomized Trial Evidence.Health science reports · 2026Article
- The membrane-associated ubiquitin ligase MARCHF8 degrades MHC-I in HPV-positive head and neck cancer for immune evasion.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Exploring Metabolic and Immunological Biomarkers for Oral Squamous Cell Carcinoma: Potential Targets for Precision Therapy.Biology · 2025Review
- An oral heme oxygenase inhibitor targets immunosuppressive perivascular macrophages in preclinical models of cancer.Science translational medicine · 2025Article
- Artificial intelligence-based digital pathology using H&E-stained whole slide images in immuno-oncology: from immune biomarker detection to immunotherapy response prediction.Journal for immunotherapy of cancer · 2025Review
- A pilot study investigating the effect of pembrolizumab on the tumoral immunoprofile of newly diagnosed mullerian cancers.Gynecologic oncology reports · 2025Article
220 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 7 institutions in 8 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIpilimumab, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4, has demonstrated an improvement in overall survival in two phase III trials of patients with advanced melanoma. The primary objective of the current trial was to prospectively explore candidate biomarkers from the tumor microenvironment for associations with clinical response to ipilimumab.
methodsIn this randomized, double-blind, phase II biomarker study (ClinicalTrials.gov NCT00261365), 82 pretreated or treatment-naïve patients with unresectable stage III/IV melanoma were induced with 3 or 10 mg/kg ipilimumab every 3 weeks for 4 doses; at Week 24, patients could receive maintenance doses every 12 weeks. Efficacy was evaluated per modified World Health Organization response criteria and safety was assessed continuously. Candidate biomarkers were evaluated in tumor biopsies collected pretreatment and 24 to 72 hours after the second ipilimumab dose. Polymorphisms in immune-related genes were also evaluated.
resultsObjective response rate, response patterns, and safety were consistent with previous trials of ipilimumab in melanoma. No associations between genetic polymorphisms and clinical activity were observed. Immunohistochemistry and histology on tumor biopsies revealed significant associations between clinical activity and high baseline expression of FoxP3 (p = 0.014) and indoleamine 2,3-dioxygenase (p = 0.012), and between clinical activity and increase in tumor-infiltrating lymphocytes (TILs) between baseline and 3 weeks after start of treatment (p = 0.005). Microarray analysis of mRNA from tumor samples taken pretreatment and post-treatment demonstrated significant increases in expression of several immune-related genes, and decreases in expression of genes implicated in cancer and melanoma.
conclusionsBaseline expression of immune-related tumor biomarkers and a post-treatment increase in TILs may be positively associated with ipilimumab clinical activity. The observed pharmacodynamic changes in gene expression warrant further analysis to determine whether treatment-emergent changes in gene expression may be associated with clinical efficacy. Further studies are required to determine the predictive value of these and other potential biomarkers associated with clinical response to ipilimumab.
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Registered trials
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.