Trial reportJournal for immunotherapy of cancer2020
An open-label, phase II multicohort study of an oral hypomethylating agent CC-486 and durvalumab in advanced solid tumors.
Trial report in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02811497 (An Open-label, Phase II Basket Study of a hypoMEThylating Agent Oral Azacitidine and DURvalumab), which is not on this map. Cited by 45 papers, 3 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 Open-label, Phase II Basket Study of a hypoMEThylating Agent Oral Azacitidine and DURvalumab (MEDI4736) (Anti-PDL1) in Advanced Solid Tumors (METADUR)
Who cites it
45 citing papers in PubMed, 3 syntheses or guidelines pooled it, 68 citations in OpenAlex.
- The Efficacy of Immune Checkpoint Inhibitors in Microsatellite Stable Colorectal Cancer: A Systematic Review.The oncologist · 2024Pooled it
- Evolution of Immunotherapy for Ovarian Cancer from a Bird's-Eye Perspective: A Text-Mining Analysis of Publication Trends and Topics.Frontiers in oncology · 2022Pooled it
- Targeted drug delivery system for ovarian cancer microenvironment: Improving the effects of immunotherapy.Frontiers in immunology · 2022Pooled it
- Pembrolizumab plus azacitidine in patients with chemotherapy refractory metastatic colorectal cancer: a single-arm phase 2 trial and correlative biomarker analysis.Clinical epigenetics · 2022Trial
- Transposable Element Activation: A Hallmark of Cancer.Cancer discovery · 2026Review
- Review
- Pembrolizumab and epigenetic modification with azacitidine reshapes the tumor microenvironment of platinum-resistant epithelial ovarian cancer: a phase 2 non-randomized clinical trial.Communications medicine · 2026Article
- Endogenous retroviruses and response to immune checkpoint inhibitors: mechanisms, clinical evidence, and therapeutic implications.Frontiers in immunology · 2026Review
- Senescence-associated and immune-related 9p21.3 locus genes in colorectal cancer: epigenetic architecture, molecular landscape and therapeutic possibilities.Frontiers in cell and developmental biology · 2026Review
- Epigenetic Regulation of Immune Responses in Endocrine-Related Cancers and Its Role in Immunotherapy.Cancers · 2025Review
- Epi-Immunotherapy in Cancer Treatment: Mechanisms, Clinical Progress, and Future Directions.Cancer innovation · 2025Review
- Near-infrared light-induced photothermal and immunotherapy system for lung cancer bone metastasis treatment with simultaneous bone repair.Bioactive materials · 2025Article
- Analysis of IDH1 and IDH2 mutations as causes of the hypermethylator phenotype in colorectal cancer.The Journal of pathology · 2025Article
- Review
- Review
- Review
- Unveiling the immunomodulatory dance: endothelial cells' function and their role in non-small cell lung cancer.Molecular cancer · 2025Review
- An Open-Label Phase II Trial of Pembrolizumab, an Immune Checkpoint Inhibitor Alone or in Combination With Oral Azacitidine as Second-Line Therapy for Advanced Head and Neck Squamous Cell Cancers.Health science reports · 2025Article
- Clinical application of PBMCs in breast cancer: detection, treatment evaluation and prognosis.Frontiers in cell and developmental biology · 2025Review
- Immunotherapy for hormone receptor‒positive HER2-negative breast cancer.NPJ breast cancer · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 3 institutions in 1 country.
Funding
Abstract
purposeTo evaluate whether administration of the oral DNA hypomethylating agent CC-486 enhances the poor response rate of immunologically 'cold' solid tumors to immune checkpoint inhibitor durvalumab. EXPERIMENTAL
designPD-L1/PD-1 inhibitor naïve patients with advanced microsatellite stable colorectal cancer; platinum resistant ovarian cancer; and estrogen receptor positive, HER2 negative breast cancer were enrolled in this single-institution, investigator-initiated trial. Two 28 day regimens, regimen A (CC-486 300 mg QD Days 1-14 (cycles 1-3 only) in combination with durvalumab 1500 mg intravenous day 15) and regimen B (CC-486 100 mg QD days 1-21 (cycle 1 and beyond), vitamin C 500 mg once a day continuously and durvalumab 1500 mg intravenous day 15) were investigated. Patients underwent paired tumor biopsies and serial peripheral blood mononuclear cells (PBMCs) collection for immune-profiling, transcriptomic and epigenomic analyzes.
resultsA total of 28 patients were enrolled, 19 patients treated on regimen A and 9 on regimen B. The combination of CC-486 and durvalumab was tolerable. Regimen B, with a lower dose of CC-486 extended over a longer treatment course, showed less grade 3/4 adverse effects. Global LINE-1 methylation assessment of serial PBMCs and genome-wide DNA methylation profile in paired tumor biopsies demonstrated minimal changes in global methylation in both regimens. The lack of robust tumor DNA demethylation was accompanied by an absence of the expected 'viral mimicry' inflammatory response, and consequently, no clinical responses were observed. The disease control rate was 7.1%. The median progression-free survival was 1.9 months (95% CI 1.5 to 2.3) and median overall survival was 5 months (95% CI 4.5 to 10).
conclusionsThe evaluated treatment schedules of CC-486 in combination with durvalumab did not demonstrate robust pharmacodynamic or clinical activity in selected immunologically cold solid tumors. Lessons learned from this biomarker-rich study should inform continued drug development efforts using these agents. TRIAL REGISTRATION NUMBER: NCT02811497.
Indexed as
Identifiers
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.