ArticleJournal for immunotherapy of cancer2022
Safety, tolerability and efficacy of agonist anti-CD27 antibody (varlilumab) administered in combination with anti-PD-1 (nivolumab) in advanced solid tumors.
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 NCT02335918 (A Phase l/ll Dose Escalation and Cohort Expansion Study of the Safety, Tolerability and Efficacy of Anti-CD27 Antibody), which is not on this map. Cited by 50 papers, 2 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 l/ll Dose Escalation and Cohort Expansion Study of the Safety, Tolerability and Efficacy of Anti-CD27 Antibody (Varlilumab) Administered in Combination With Anti-PD-1 (Nivolumab) in Advanced Refractory Solid Tumors
Who cites it
50 citing papers in PubMed, 2 syntheses or guidelines pooled it, 64 citations in OpenAlex.
- Safety of immune checkpoint modulators beyond PD-1/PD-L1 and CTLA-4 in solid tumors: a meta-analysis.JNCI cancer spectrum · 2026Pooled it
- Mendelian randomization identifies multiple immune cell surface markers as potential causal contributors and drug targets in rheumatoid arthritis.The Journal of international medical research · 2026Pooled it
- 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
- Randomized Phase I/II Clinical Trial of a Melanoma Helper Peptide Vaccine with or without Systemic Agonistic Anti-CD27 Antibody (Varlilumab).Cancer research communications · 2026Trial
- CD27 Agonist Antibodies Mediate Clinical Responses through Intratumoral Stimulation in B-cell Malignancies: Multicenter RiVa Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- A combinatory vaccine with IMA950 plus varlilumab promotes effector memory T-cell differentiation in the peripheral blood of patients with low-grade gliomas.Neuro-oncology · 2024Trial
- Innovative immunotherapy approaches: harnessing synergy of dual checkpoint blockade in oncology.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- CD27 expression is a clinically accessible biomarker for predicting immunotherapy response in melanoma.NPJ precision oncology · 2026Article
- T-Cell Immunity and Lung Cancer.Respirology (Carlton, Vic.) · 2026Review
- CD27 and ICOS as Targets of PD-1/PD-L1 Signaling to Regulate Resident Memory CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A Comprehensive Review of Immunotherapeutic Modalities in Glioblastoma: Mechanisms, Efficacy, and Safety ConsiderationsCancers · 2026Review
- A novel mRNA-based therapeutic vaccine elicits robust anti-tumor immunity against HPV-associated malignancies.Frontiers in immunology · 2026Article
- Pan cohort immune biomarker of CD8 lymphocyte activation enabling HGSOC outcome prediction and treatment response.Discover oncology · 2025Article
- Harnessing multivalency and FcγRIIB engagement to augment anti-CD27 immunotherapy.Nature communications · 2025Article
- Unlocking new frontiers: novel immune targets for next-generation cancer immunotherapy.Korean journal of clinical oncology · 2025Review
- A hexamerization-enhanced, Fc-silenced agonistic CD27 antibody amplifies T-cell effector functions as single agent and in combination with PD-1 blockade.Scientific reports · 2025Article
- Focus on PD-1/PD-L1-Targeting Antibodies in Colorectal Cancer: Are There Options Beyond Dostarlimab, Nivolumab, and Pembrolizumab? A Comprehensive Review.Molecules (Basel, Switzerland) · 2025Review
- Review
- Targeting novel regulated cell death: disulfidptosis in cancer immunotherapy with immune checkpoint inhibitors.Biomarker research · 2025Review
- Combining immune checkpoints with TNFSF agonists: a new horizon for cancer and autoimmune therapies.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
24 authors at 17 institutions in 1 country.
Funding
Abstract
backgroundPhase 1/2 dose-escalation and expansion study evaluating varlilumab, a fully human agonist anti-CD27 mAb, with nivolumab in anti-PD-1/L1 naïve, refractory solid tumors.
methodsPhase 1 evaluated the safety of varlilumab (0.1-10 mg/kg) with nivolumab (3 mg/kg) administered once every 2 weeks. Phase 2 evaluated varlilumab regimens (3 mg/kg once every 2 weeks, 3 mg/kg once every 12 weeks, and 0.3 mg/kg once every 4 weeks) with nivolumab 240 mg once every 2 weeks in tumor-specific cohorts. Primary objective was safety; key clinical endpoints included objective response rate (ORR) and overall survival rate at 12 months (OS12) (glioblastoma (GBM) only). Exploratory objectives included determination of effects on peripheral blood and intratumoral immune signatures.
results175 patients were enrolled (36 in phase 1 and 139 in phase 2). Phase 1 dose-escalation proceeded to the highest varlilumab dose level without determining a maximum tolerated dose. In phase 2, ORR were ovarian 12.5%, squamous cell carcinoma of the head and neck 12.5%, colorectal cancer 5%, and renal cell carcinoma 0%; GBM OS12 was 40.9%. Increased tumor PD-L1 and intratumoral T cell infiltration were observed in ovarian cancer patients, with increases of ≥5% associated with better progression-free survival. The most common treatment related adverse events were fatigue (18%), pruritus (16%), and rash (15%).
conclusionVarlilumab and nivolumab were well tolerated, without significant toxicity beyond that expected for each agent alone. Clinical activity was observed in patients that are typically refractory to anti-PD-1 therapy, however, overall was not greater than expected for nivolumab monotherapy. Treatment was associated with proinflammatory changes in the tumor microenvironment, particularly in ovarian cancer where the changes were associated with better clinical outcomes. TRIAL REGISTRATION NUMBER: NCT02335918.
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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.