ArticleJournal for immunotherapy of cancer2019
Safety, tolerability, pharmacokinetics, and pharmacodynamics of the afucosylated, humanized anti-EPHA2 antibody DS-8895a: a first-in-human phase I dose escalation and dose expansion study in patients with advanced solid tumors.
Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02004717 (Phase 1, Open-label Study to Assess the Safety, Tolerability, and Pharmacokinetics of DS-8895a in Subjects With Advanced Solid Tumors), which is not on this map. Cited by 26 papers.
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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.
Phase 1, Open-label Study to Assess the Safety, Tolerability, and Pharmacokinetics of DS-8895a in Subjects With Advanced Solid Tumors
Who cites it
26 citing papers in PubMed, 31 citations in OpenAlex.
- Bioengineered extracellular vesicles integrating anti-EphA2 recognition and oxaliplatin delivery for pancreatic cancer therapy.Drug delivery · 2026Article
- Antitumor Activities of Chimeric Anti-EphA2 Antibodies in Xenograft Models of Breast, Pancreatic, and Colorectal Cancers.International journal of molecular sciences · 2026Article
- Unlocking the potential of EphA2 with precision-guided cancer therapy: bicycle drug conjugates.Journal of translational medicine · 2026Review
- Sweet Surprises: Decoding Tumor-Associated Glycosylation in Cancer Progression and Therapeutic Potential.Cells · 2026Review
- Theranostics usingEuropean journal of nuclear medicine and molecular imaging · 2025Article
- Synthetic antibodies targeting EphA2 induce diverse signaling-competent clusters with differential activation.Protein science : a publication of the Protein Society · 2025Article
- Development of a novel anti-erythropoietin-producing hepatocellular receptor B6 monoclonal antibody EbBiochemistry and biophysics reports · 2025Article
- EphA2-targeted alpha-particle theranostics for enhancing PDAC treatment.Theranostics · 2025Article
- EphA2 in Cancer: Molecular Complexity and Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- Targeting the EphA2 pathway: could it be the way for bone sarcomas?Cell communication and signaling : CCS · 2024Review
- The EphA2 Receptor Regulates Invasiveness and Drug Sensitivity in Canine and Human Osteosarcoma Cells.Cells · 2024Article
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
- Review
- Novel [ACS omega · 2023Article
- The EPH/Ephrin System in Pancreatic Ductal Adenocarcinoma (PDAC): From Pathogenesis to Treatment.International journal of molecular sciences · 2023Review
- Eph Receptors in Cancer.Biomedicines · 2023Review
- Expression characteristic, immune signature, and prognosis value of EFNA family identified by multi-omics integrative analysis in pan-cancer.BMC cancer · 2022Article
- Protein-Protein Interaction Inhibitors Targeting the Eph-Ephrin System with a Focus on Amino Acid Conjugates of Bile Acids.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Fully human recombinant antibodies against EphA2 from a multi-tumor patient immune library suitable for tumor-targeted therapy.Bioengineered · 2021Article
- Article
Corrections and comments
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Authors and funding
15 authors at 11 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundErythropoietin-producing hepatocellular receptor A2 (EPHA2) is overexpressed on the cell surface in many cancers and predicts poor prognosis. DS-8895a is a humanized anti-EPHA2 IgG1 monoclonal antibody afucosylated to enhance antibody-dependent cellular cytotoxicity activity. We conducted a two-step, phase I, multicenter, open-label study to determine the safety, tolerability, and pharmacokinetics of DS-8895a in patients with advanced solid tumors.
methodsStep 1 was a dose escalation cohort in advanced solid tumor patients (six dose levels, 0.1-20 mg/kg) to determine Step 2 dosing. Step 2 was a dose expansion cohort in EPHA2-positive esophageal and gastric cancer patients. DS-8895a was intravenously administered every 2 weeks for the duration of the study, with a 28-day period to assess dose-limiting toxicity (DLT). Safety, pharmacokinetics, tumor response, and potential biomarkers were evaluated.
resultsThirty-seven patients (Step 1: 22, Step 2: 15 [9: gastric cancer, 6: esophageal cancer]) were enrolled. Although one DLT (Grade 4 platelet count decreased) was observed in Step 1 (dose level 6, 20 mg/kg), the maximum tolerated dose was not reached; the highest dose (20 mg/kg) was used in Step 2. Of the 37 patients, 24 (64.9%) experienced drug-related adverse events (AEs) including three (8.1%) with Grade ≥ 3 AEs. Infusion-related reactions occurred in 19 patients (51.4%) but were manageable. All patients discontinued the study (evident disease progression, 33; AEs, 4). Maximum and trough serum DS-8895a concentrations increased dose-dependently. One gastric cancer patient achieved partial response and 13 patients achieved stable disease. Serum inflammatory cytokines transiently increased at completion of and 4 h after the start of DS-8895a administration. The proportion of CD16-positive natural killer (NK) cells (CD3
conclusionsTwenty mg/kg DS-8895a infused intravenously every 2 weeks was generally safe and well tolerated in patients (n = 21) with advanced solid tumors. The exposure of DS-8895a seemed to increase dose-dependently and induce activated NK cells.
trial registrationPhase 1 Study of DS-8895a in patients with advanced solid tumors ( NCT02004717 ; 7 November 2013 to 2 February 2017); retrospectively registered on 9 December 2013.
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