Trial reportJournal of clinical oncology : official journal of the American Society of Clinical Oncology2019
First-Line Nivolumab Plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer (CheckMate 568): Outcomes by Programmed Death Ligand 1 and Tumor Mutational Burden as Biomarkers.
Trial report in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04250246 (A Randomized, run-in, Multi-center, Phase II Study of Nivolumab Combined With Ipilimumab and Guadecitabine or Nivolumab Combined With Ipilimumab in Melanoma and NSCLC Patients Resistant to Anti-PD-1/PD-L1), which is not on this map. Cited by 361 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.
A Randomized, run-in, Multi-center, Phase II Study of Nivolumab Combined With Ipilimumab and Guadecitabine or Nivolumab Combined With Ipilimumab in Melanoma and NSCLC Patients Resistant to Anti-PD-1/PD-L1 (NIBIT-ML1)
Who cites it
361 citing papers in PubMed, 11 syntheses or guidelines pooled it, 589 citations in OpenAlex.
- Pretreatment CT Texture Analysis for Predicting Survival Outcomes in Advanced Nonsmall Cell Lung Cancer Patients Receiving Immunotherapy: A Systematic Review and Meta-Analysis.Thoracic cancer · 2025Pooled it
- Evaluating Tumour Mutational Burden as a Key Biomarker in Personalized Cancer Immunotherapy: A Pan-Cancer Systematic Review.Cancers · 2025Pooled it
- Efficacy and safety of first-line PD-1/PD-L1 inhibitor in combination with CTLA-4 inhibitor in the treatment of patients with advanced non-small cell lung cancer: a systemic review and meta-analysis.Frontiers in immunology · 2025Pooled it
- Risk and safety profile in checkpoint inhibitors on non-small-cel lung cancer: A systematic review.Human vaccines & immunotherapeutics · 2024Pooled it
- A meta-analysis of the efficacy of programmed cell death 1/its ligand inhibitors plus cytotoxic T-lymphocyte-associated antigen 4 inhibitors in non-small cell lung cancer.Frontiers in pharmacology · 2024Pooled it
- PD-1/PD-L1 inhibitors in treatment-naïve, advanced non-small cell lung cancer patients with < 1% PD-L1 expression: a meta-analysis of randomized controlled trials.Journal of cancer research and clinical oncology · 2023Pooled it
- Efficacy and safety of PD-1/PD-L1 plus CTLA-4 antibodies ± other therapies in lung cancer: a systematic review and meta-analysis.European journal of hospital pharmacy : science and practice · 2023Pooled it
- Deciphering radiological stable disease to immune checkpoint inhibitors.Annals of oncology : official journal of the European Society for Medical Oncology · 2022Pooled it
- Pooled it
- Risk of Adverse Events in Cancer Patients Receiving Nivolumab With Ipilimumab: A Meta-Analysis.Frontiers in oncology · 2022Pooled it
- Predictive value of tumor mutational burden for immunotherapy in non-small cell lung cancer: A systematic review and meta-analysis.PloS one · 2022Pooled it
- Neoantigen-specific tumor-infiltrating lymphocytes in gastrointestinal cancers: a phase 2 trial.Nature medicine · 2025Trial
- Nivolumab plus low-dose ipilimumab in hypermutated HER2-negative metastatic breast cancer: a phase II trial (NIMBUS).Nature communications · 2025Trial
- Trial
- Noninvasive early identification of durable clinical benefit from immune checkpoint inhibition: a prospective multicenter study (NCT04566432).Signal transduction and targeted therapy · 2024Trial
- Randomized, open-label, phase 2 study of nivolumab plus ipilimumab or nivolumab monotherapy in patients with advanced or metastatic solid tumors of high tumor mutational burden.Journal for immunotherapy of cancer · 2024Trial
- Camrelizumab plus famitinib in previously chemo-immunotherapy treated patients with advanced NSCLC: results from an open-label multicenter phase 2 basket study.Cancer immunology, immunotherapy : CII · 2024Trial
- First-line treatment with camrelizumab plus famitinib in advanced or metastatic NSCLC patients with PD-L1 TPS ≥1%: results from a multicenter, open-label, phase 2 trial.Journal for immunotherapy of cancer · 2024Trial
- Durvalumab ± Tremelimumab + Platinum-Etoposide in Extensive-Stage Small Cell Lung Cancer (CASPIAN): Outcomes by PD-L1 Expression and Tissue Tumor Mutational Burden.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Nivolumab plus ipilimumab in advanced salivary gland cancer: a phase 2 trial.Nature medicine · 2023Trial
301 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
28 authors at 20 institutions in 6 countries.
Funding
Abstract
purposeCheckMate 568 is an open-label phase II trial that evaluated the efficacy and safety of nivolumab plus low-dose ipilimumab as first-line treatment of advanced/metastatic non-small-cell lung cancer (NSCLC). We assessed the association of efficacy with programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB). PATIENTS AND
methodsTwo hundred eighty-eight patients with previously untreated, recurrent stage IIIB/IV NSCLC received nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks. The primary end point was objective response rate (ORR) in patients with 1% or more and less than 1% tumor PD-L1 expression. Efficacy on the basis of TMB (FoundationOne CDx assay) was a secondary end point.
resultsOf treated patients with tumor available for testing, 252 patients (88%) of 288 were evaluable for PD-L1 expression and 98 patients (82%) of 120 for TMB. ORR was 30% overall and 41% and 15% in patients with 1% or greater and less than 1% tumor PD-L1 expression, respectively. ORR increased with higher TMB, plateauing at 10 or more mutations/megabase (mut/Mb). Regardless of PD-L1 expression, ORRs were higher in patients with TMB of 10 or more mut/Mb (n = 48: PD-L1, ≥ 1%, 48%; PD-L1, < 1%, 47%) versus TMB of fewer than 10 mut/Mb (n = 50: PD-L1, ≥ 1%, 18%; PD-L1, < 1%, 5%), and progression-free survival was longer in patients with TMB of 10 or more mut/Mb versus TMB of fewer than 10 mut/Mb (median, 7.1
conclusionNivolumab plus low-dose ipilimumab was effective and tolerable as a first-line treatment of advanced/metastatic NSCLC. TMB of 10 or more mut/Mb was associated with improved response and prolonged progression-free survival in both tumor PD-L1 expression 1% or greater and less than 1% subgroups and was thus identified as a potentially relevant cutoff in the assessment of TMB as a biomarker for first-line nivolumab plus 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.