Trial reportThe Journal of clinical investigation2021
Multicenter randomized phase II trial of atezolizumab with or without cobimetinib in biliary tract cancers.
Trial report in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03201458 (A Randomized Phase 2 Study of Atezolizumab in Combination With Cobimetinib Versus Atezolizumab Monotherapy in Participants With Unresectable Cholangiocarcinoma), which is not on this map. Cited by 81 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 Randomized Phase 2 Study of Atezolizumab in Combination With Cobimetinib Versus Atezolizumab Monotherapy in Participants With Unresectable Cholangiocarcinoma
Who cites it
81 citing papers in PubMed, 4 syntheses or guidelines pooled it, 80 citations in OpenAlex.
- Beta-blockers improve neurological outcomes of cerebral cavernous malformations: a systematic review.Neurosurgical review · 2026Pooled it
- Efficacy and safety of targeted therapy and immune checkpoint inhibitors in patients with advanced or metastatic biliary tract cancer: a meta-analysis of and sequential analysis of trials.Hepatology international · 2025Pooled it
- Significant association between HIV infection and increased risk of COVID-19 mortality: a meta-analysis based on adjusted effect estimates.Clinical and experimental medicine · 2023Pooled it
- Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of gastrointestinal cancer.Journal for immunotherapy of cancer · 2023Guideline
- A Randomized Phase II Study of Combination Atezolizumab and Varlilumab (CDX-1127) with or without Cobimetinib in Previously Treated Unresectable Biliary Tract Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- The multi-kinase inhibitor tinengotinib as monotherapy or combined with atezolizumab in advanced solid tumors: a phase Ib/II trial.Nature communications · 2026Trial
- Atezolizumab Plus Chemotherapy With or Without Bevacizumab in Advanced Biliary Tract Cancer: Clinical and Biomarker Data From the Randomized Phase II IMbrave151 Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Combined MEK/PD-L1 Inhibition Alters Peripheral Cytokines and Lymphocyte Populations Correlating with Improved Clinical Outcomes in Advanced Biliary Tract Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- VNN1, upregulated by FOXA1, suppresses osteogenic differentiation and promotes inflammation in LPS-induced periodontal ligament stem cells.Odontology · 2026Article
- Dyslipidaemia and hepatic steatosis: mechanisms and implications for lipid-lowering therapy.Nature reviews. Cardiology · 2026Review
- Identification of new protein-coding potential in Leishmania donovani using a proteogenomics approach.Current microbiology · 2026Article
- Advances in Immunotherapy for Intrahepatic Cholangiocarcinoma.International journal of molecular sciences · 2026Review
- Tumor site influences efficacy of MEKi and immunotherapy combinations in a preclinical model of cholangiocarcinoma.Hepatology (Baltimore, Md.) · 2026Article
- CAR-T cells directed toward PD-L1 demonstrate potent, antigen-specific activity against cholangiocarcinoma: A proof of concept study.Molecular therapy. Oncology · 2026Article
- Exercise-induced modulation of the unfolded protein response: a therapeutic avenue for muscle wasting disorders.Journal of physiology and biochemistry · 2026Review
- From bench to bedside: stem cell therapy as a transformative approach against HIV.Molecular biology reports · 2026Review
- Development of a murine tumor-infiltrating lymphocyte therapy model for cholangiocarcinoma.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Advancing systemic therapy for biliary tract cancer: current strategies and emerging paradigms.Frontiers in oncology · 2026Review
- Hic-5 deficiency attenuates MAFLD by inhibiting neutrophils migration via the CXCL1-CXCR2 axis.Journal of gastroenterology · 2025Article
- A Comprehensive Analysis of Novel Variations Associated with Bile Duct Cancer: Insights into Expression, Methylation, and 3D Protein Structure.International journal of molecular sciences · 2025Article
21 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
29 authors at 18 institutions in 1 country.
Funding
Abstract
BACKGROUNDMEK inhibitors have limited activity in biliary tract cancers (BTCs) as monotherapy but are hypothesized to enhance responses to programmed death ligand 1 (PD-L1) inhibition.METHODSThis open-label phase II study randomized patients with BTC to atezolizumab (anti-PD-L1) as monotherapy or in combination with cobimetinib (MEK inhibitor). Eligible patients had unresectable BTC with 1 to 2 lines of prior therapy in the metastatic setting, measurable disease, and Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1. The primary endpoint was progression-free survival (PFS).RESULTSSeventy-seven patients were randomized and received study therapy. The trial met its primary endpoint, with a median PFS of 3.65 months in the combination arm versus 1.87 months in the monotherapy arm (HR 0.58, 90% CI 0.35-0.93, 1-tail P = 0.027). One patient in the combination arm (3.3%) and 1 patient in the monotherapy arm (2.8%) had a partial response. Combination therapy was associated with more rash, gastrointestinal events, CPK elevations, and thrombocytopenia. Exploratory analysis of tumor biopsies revealed enhanced expression of antigen processing and presentation genes and an increase in CD8/FoxP3 ratios with combination treatment. Patients with higher baseline or lower fold changes in expression of certain inhibitory ligands (LAG3, BTLA, VISTA) on circulating T cells had evidence of greater clinical benefit from the combination.CONCLUSIONThe combination of atezolizumab plus cobimetinib prolonged PFS as compared with atezolizumab monotherapy, but the low response rate in both arms highlights the immune-resistant nature of BTCs.TRIAL REGISTRATIONClinicalTrials.gov NCT03201458.FUNDINGNational Cancer Institute (NCI) Experimental Therapeutics Clinical Trials Network (ETCTN); F. Hoffmann-La Roche, Ltd.; NCI, NIH (R01 CA228414-01 and UM1CA186691); NCI's Specialized Program of Research Excellence (SPORE) in Gastrointestinal Cancers (P50 CA062924); NIH Center Core Grant (P30 CA006973); and the Passano Foundation.
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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.