Trial reportNature medicine2023
Ipilimumab with or without nivolumab in PD-1 or PD-L1 blockade refractory metastatic melanoma: a randomized phase 2 trial.
Trial report in Nature medicine, 2023. 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 120 papers, 4 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.
A Phase II Randomized Study of Nivolumab (NSC-748726) With Ipilimumab (NSC-732442) or Ipilimumab Alone in Advanced Melanoma Patients Refractory to an Anti-PD1 or Anti-PD-L1 Agent
Phase II Study of Neoadjuvant Ipilimumab/Nivolumab for Patients With Recurrent, High Risk, Resectable Melanoma
Who cites it
120 citing papers in PubMed, 4 syntheses or guidelines pooled it, 154 citations in OpenAlex.
- Updated pan-tumor guidelines for neoadjuvant scoring of pathologic response: a joint SITC and INMC effort.Annals of oncology : official journal of the European Society for Medical Oncology · 2026Guideline
- Cutaneous melanoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.Annals of oncology : official journal of the European Society for Medical Oncology · 2025Guideline
- SEOM-GEM clinical guidelines for cutaneous melanoma (2023).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Guideline
- Prognostic value of inflammatory markers NLR, PLR, LMR, dNLR, ANC in melanoma patients treated with immune checkpoint inhibitors: a meta-analysis and systematic review.Frontiers in immunology · 2024Pooled it
- Cellular Neighborhoods Govern Antitumor T-cell Infiltration Following Anti-CTLA-4 in Melanoma with Primary Resistance to Anti-PD-1.Cancer discovery · 2026Trial
- MONETTE: A Randomized Phase II Study of Ceralasertib plus Durvalumab or Ceralasertib Monotherapy in Patients with Advanced Melanoma Resistant to PD-(L)1 Inhibition.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Surufatinib plus toripalimab for patients with advanced solid tumors and disease progression after prior immunotherapy: an open-label multi-cohort phase 2 trial.Cancer immunology, immunotherapy : CII · 2026Trial
- RP1 Combined With Nivolumab in Advanced Anti-PD-1-Failed Melanoma (IGNYTE).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- FDA Approval Summary: Lifileucel for Unresectable or Metastatic Melanoma Previously Treated with an Anti-PD-1-Based Immunotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- BO-112 Plus Pembrolizumab for Patients With Anti-PD-1-Resistant Advanced Melanoma: Phase II Clinical Trial SPOTLIGHT-203.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Three-Year Overall Survival With Nivolumab Plus Relatlimab in Advanced Melanoma From RELATIVITY-047.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Intratumoral delivery of PD-1/PD-L1 and CTLA-4 inhibitors for recurrent/refractory solid tumors: a proof-of-concept treatment strategy.Frontiers in immunology · 2025Trial
- Real-World Outcomes of Nivolumab and Ipilimumab in Metastatic Melanoma as Third Line and Beyond.International journal of cancer · 2026Article
- ATR inhibition induces NF-κB-dependent immunogenicity in Merkel cell carcinoma independent of cGAS-STING.NPJ precision oncology · 2026Article
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- Phase I trial of a heat-conditioned tumor lysate vaccine (TRIMELVax) in anti-PD-1 refractory melanoma: safety and immunological aspects (NCT06556004).British journal of cancer · 2026Article
- Tailored FcγR blockade enhances immune checkpoint therapy and overcomes resistance.Journal of experimental & clinical cancer research : CR · 2026Article
- Evaluation of the flipped dose NIVO3+IPI1 in patients with advanced unresectable melanoma.Journal of the National Cancer Institute · 2026Article
- An immunogenomic classification of solid tumours reveals subtype-specific therapeutic vulnerabilities for immunotherapy.EBioMedicine · 2026Article
- Multidrug resistance in cancer: current understandings and future perspective.Molecular biomedicine · 2026Review
60 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
33 authors at 19 institutions in 1 country.
Funding
Abstract
In this randomized phase 2 trial, blockade of cytotoxic T-lymphocyte protein 4 (CTLA-4) with continuation of programmed death protein 1 (PD-1) blockade in patients with metastatic melanoma who had received front-line anti-PD-1 or therapy against programmed cell death 1 ligand 1 and whose tumors progressed was tested in comparison with CTLA-4 blockade alone. Ninety-two eligible patients were randomly assigned in a 3:1 ratio to receive the combination of ipilimumab and nivolumab, or ipilimumab alone. The primary endpoint was progression-free survival. Secondary endpoints included the difference in CD8 T cell infiltrate among responding and nonresponding tumors, objective response rate, overall survival and toxicity. The combination of nivolumab and ipilimumab resulted in a statistically significant improvement in progression-free survival over ipilimumab (hazard ratio = 0.63, 90% confidence interval (CI) = 0.41-0.97, one-sided P = 0.04). Objective response rates were 28% (90% CI = 19-38%) and 9% (90% CI = 2-25%), respectively (one-sided P = 0.05). Grade 3 or higher treatment-related adverse events occurred in 57% and 35% of patients, respectively, which is consistent with the known toxicity profile of these regimens. The change in intratumoral CD8 T cell density observed in the present analysis did not reach statistical significance to support the formal hypothesis tested as a secondary endpoint. In conclusion, primary resistance to PD-1 blockade therapy can be reversed in some patients with the combination of CTLA-4 and PD-1 blockade. Clinicaltrials.gov identifier: NCT03033576 .
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What OpenQuestion holds
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.