ArticleJournal for immunotherapy of cancer2022
Spartalizumab or placebo in combination with dabrafenib and trametinib in patients with
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02967692 (A Randomized, Double-blind, Placebo-controlled, Phase III Study Comparing the Combination of PDR001, Dabrafenib and Trametinib Versus Placebo, Dabrafenib and Trametinib in Previously Untreated Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma), which is not on this map. Cited by 21 papers, 2 of them syntheses that pooled it.
What it found
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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, Double-blind, Placebo-controlled, Phase III Study Comparing the Combination of PDR001, Dabrafenib and Trametinib Versus Placebo, Dabrafenib and Trametinib in Previously Untreated Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma
Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 24 citations in OpenAlex.
- Predictive value of serum biomarkers for survival in melanoma: a systematic review and meta-analysis.Scientific reports · 2026Pooled it
- The prognostic value of circulating tumor DNA in malignant melanoma patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.Frontiers in immunology · 2024Pooled it
- COMBI-I: Long-Term Overall Survival With Spartalizumab Plus Dabrafenib and Trametinib inJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026Trial
- Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial.Nature medicine · 2023Trial
- Multi-cohort validation ofTranslational cancer research · 2026Article
- Circulating Tumor DNA as a Biomarker for Melanoma Prognosis and Therapy.American journal of clinical dermatology · 2026Review
- Anti-PD-1 Combinations: Triplets and Beyond.Current oncology reports · 2026Review
- Neoantigen Targeting as a Novel Approach for Therapy-Resistant Tumors.Molecular diagnosis & therapy · 2026Review
- Review
- Fragment-based discovery enables direct targeting of the melanoma oncogene MITF.Nature communications · 2025Article
- Immune-based cancer therapies: mechanistic insights, clinical progress, and future directions.Journal of the Egyptian National Cancer Institute · 2025Review
- Exosomal biomarkers and immune checkpoint inhibitors: advancements and future prospects.Cancer cell international · 2025Review
- Review
- Immunomodulation on tumor immune microenvironment in acquired targeted therapy resistance and implication for immunotherapy resistance.Translational oncology · 2025Review
- Therapeutic implications of the metabolic changes associated with BRAF inhibition in melanoma.Cancer treatment reviews · 2024Review
- Unravelling immune microenvironment features underlying tumor progression in the single-cell era.Cancer cell international · 2024Review
- Primary Cutaneous Melanoma-Management in 2024.Journal of clinical medicine · 2024Article
- Review
- Advances in targeted therapy and immunotherapy for melanoma (Review).Experimental and therapeutic medicine · 2023Review
- Combination of immune-checkpoint inhibitors and targeted therapies for melanoma therapy: The more, the better?Cancer metastasis reviews · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 11 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe randomized phase 3 COMBI-i trial did not meet its primary endpoint of improved progression-free survival (PFS) with spartalizumab plus dabrafenib and trametinib (sparta-DabTram) vs placebo plus dabrafenib and trametinib (placebo-DabTram) in the overall population of patients with unresectable/metastatic
methodsIn COMBI-i (ClinicalTrials.gov, NCT02967692), 532 patients received spartalizumab 400 mg intravenously every 4 weeks plus dabrafenib 150 mg orally two times daily and trametinib 2 mg orally one time daily or placebo-DabTram. Baseline/on-treatment pharmacodynamic markers were assessed via flow cytometry-based immunophenotyping and plasma cytokine profiling. Baseline programmed death ligand 1 (PD-L1) status and T-cell phenotype were assessed via immunohistochemistry;
resultsExtensive biomarker analyses were possible in approximately 64% to 90% of the intention-to-treat population, depending on sample availability and assay. Subgroups based on PD-L1 status/TMB or T-cell inflammation did not show significant differences in PFS benefit with sparta-DabTram vs placebo-DabTram, although T-cell inflammation was prognostic across treatment arms. Subgroups defined by
conclusionsThese results support the feasibility of large-scale comprehensive biomarker analyses in the context of a global phase 3 study. T-cell inflammation was prognostic but not predictive of sparta-DabTram benefit, as patients with high T-cell inflammation already benefit from targeted therapy alone. Baseline ctDNA shedding also emerged as a strong independent prognostic variable, with predictive trends consistent with established measures of disease burden such as lactate dehydrogenase levels. CD4 TRIAL REGISTRATION NUMBER: NCT02967692.
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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.