ArticleOncoimmunology
Long-term outcomes of a phase I study of agonist CD40 antibody and CTLA-4 blockade in patients with metastatic melanoma.
Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
75 citing papers in PubMed, 2 syntheses or guidelines pooled it, 120 citations in OpenAlex.
- Agonistic anti-CD40 antibodies in patients with solid tumors: a systematic review and evidence map of clinical safety, with exploratory proportional synthesis.Frontiers in immunology · 2026Pooled it
- Immune checkpoint inhibitor-associated pituitary-adrenal dysfunction: A systematic review and meta-analysis.Cancer medicine · 2019Pooled it
- A Phase 2 Study of Sotigalimab, a CD40 Agonist Antibody, plus Concurrent Chemoradiation as Neoadjuvant Therapy for Esophageal and Gastroesophageal Junction Cancers.Cancer research communications · 2025Trial
- A Phase II Trial of the CD40 Agonistic Antibody Sotigalimab (APX005M) in Combination with Nivolumab in Subjects with Metastatic Melanoma with Confirmed Disease Progression on Anti-PD-1 Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- CD40 agonism in renal cell carcinoma enhances immune checkpoint activity through myeloid cells.iScience · 2026Article
- Neoadjuvant intraprostatic immunotherapy for high-risk localized prostate cancer.Nature reviews. Urology · 2026Review
- Reduced Tumor Control in Males Can Result from Impaired CD4+ T-cell Help through the CD40L-CD40 Pathway.Cancer immunology research · 2026Article
- Article
- Agonistic CD40 elicits CD8+ T-cell-dependent primary responses and CD4+ T-cell-dependent long-term immunity in breast cancer.NPJ breast cancer · 2026Article
- CD40 agonist improves the therapeutic efficacy of irreversible electroporation ablation for metastatic melanoma by promoting unexpected CD8Cancer immunology, immunotherapy : CII · 2025Article
- Fc-optimized CD40 agonistic antibody elicits tertiary lymphoid structure formation and systemic antitumor immunity in metastatic cancer.Cancer cell · 2025Article
- Facts and Hopes of CD40 Agonists in Cancer Immunotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Integrated bioinformatic analysis identifies GADD45B as an immune-related prognostic biomarker in skin cutaneous melanoma.Hereditas · 2025Article
- Targeting the TNF and TNFR superfamilies in autoimmune disease and cancer.Nature reviews. Drug discovery · 2024Review
- The Immune Landscape of Pheochromocytoma and Paraganglioma: Current Advances and Perspectives.Endocrine reviews · 2024Review
- Intratumoral Fc-optimized agonistic CD40 antibody induces tumor rejection and systemic antitumor immunity in patients with metastatic cancer.Research square · 2024Article
- Uncovering the Potential of CD40 Agonism to Enhance Immune Checkpoint Blockade.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- A phase 1 study of the CD40 agonist MEDI5083 in combination with durvalumab in patients with advanced solid tumors.Immunotherapy · 2024Article
- Controlling Antigen Fate in Therapeutic Cancer Vaccines by Targeting Dendritic Cell Receptors.Molecular pharmaceutics · 2023Review
- Heterogeneity of the tumor immune microenvironment and clinical interventions.Frontiers of medicine · 2023Review
15 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
18 authors at 1 institution in 1 country.
Funding
Abstract
We report long-term clinical outcomes and immune responses observed from a phase 1 trial of agonist CD40 monoclonal antibody (mAb) and blocking CTLA-4 mAb in patients with metastatic melanoma. Twenty-four patients previously untreated with checkpoint blockade were enrolled. The agonistic CD40 mAb CP-870,893 and the CTLA-4 blocking mAb tremelimumab were dosed concomitantly every 3 weeks and 12 weeks, respectively, across four dose combinations. Two patients developed dose-limiting grade 3 immune-mediated colitis that led to the definition of the maximum tolerated dose (MTD). Other immune-mediated toxicity included uveitis (n = 1), hypophysitis (n = 1), hypothyroidism (n = 2), and grade 3 cytokine release syndrome (CRS) (n = 1). The estimated MTD was 0.2 mg/kg of CP-870,893 and 10 mg/kg of tremelimumab. In 22 evaluable patients, the objective response rate (ORR) was 27.3%: two patients (9.1%) had complete responses (CR) and four (18.2%) patients had partial responses (PR). With a median follow-up of 45 months, the median progression-free survival (PFS) was 3.2 months (95% CI, 1.3-5.1 months) and median overall survival (OS) was 23.6 months (95% CI, 11.7-35.5 months). Nine patients are long-term survivors (> 3 years), 8 of whom subsequently received other therapy including PD-1 mAb, surgery, or radiation therapy. Elevated baseline soluble CD25 was associated with shorter OS. Immunologically, treatment was associated with evidence of T cell activation and increased tumor T cell infiltration that was accomplished without therapeutic PD-1/PD-L1 blockade. These results suggest opportunities for immune activation and cancer immunotherapy beyond PD-1.
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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.