Trial reportCancer chemotherapy and pharmacology2015
Safety, pharmacokinetics, and pharmacodynamic properties of oral DEBIO1143 (AT-406) in patients with advanced cancer: results of a first-in-man study.
Trial report in Cancer chemotherapy and pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed.
- Trial
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- The Second Mitochondria-Derived Activator of Caspases Mimetic BI 891065 in Patients With Advanced Solid Tumors: Results From Two Phase I Studies.Cancer medicine · 2025Article
- A phase 1 trial of APG-1387, an IAP antagonist, with nab-paclitaxel and gemcitabine in patients with refractory metastatic pancreatic cancer.Cell reports. Medicine · 2025Article
- Host-directed approaches in the pursuit of a cure for HIV.Antiviral research · 2025Review
- Research Progress in the Small Molecule Smac Mimetics in Combination Therapy of Cancer.Current medicinal chemistry · 2025Review
- Inhibition of AKT enhances chemotherapy efficacy and synergistically interacts with targeting of the Inhibitor of apoptosis proteins in oesophageal adenocarcinoma.Scientific reports · 2024Article
- Multifaceted Evaluation of Inhibitors of Anti-Apoptotic Proteins in Head and Neck Cancer: Insights from In Vitro, In Vivo, and Clinical Studies (Review).Pharmaceuticals (Basel, Switzerland) · 2024Review
- Chimeric antigen receptor dendritic cells targeted delivery of a single tumoricidal factor for cancer immunotherapy.Cancer immunology, immunotherapy : CII · 2024Article
- Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.Molecular cancer · 2024Review
- The cross talk of ubiquitination and chemotherapy tolerance in colorectal cancer.Journal of cancer research and clinical oncology · 2024Review
- SMAC Mimetics for the Treatment of Lung Carcinoma: Present Development and Future Prospects.Mini reviews in medicinal chemistry · 2024Review
- The roles of E3 ubiquitin ligases in cancer progression and targeted therapy.Clinical and translational medicine · 2023Review
- Recent advances in therapeutic strategies for triple-negative breast cancer.Journal of hematology & oncology · 2022Review
- A Review of the Current Impact of Inhibitors of Apoptosis Proteins and Their Repression in Cancer.Cancers · 2022Review
- Lipopolysaccharide sensitizes the therapeutic response of breast cancer to IAP antagonist.Frontiers in immunology · 2022Article
- Clinical stage drugs targeting inhibitor of apoptosis proteins purge episomal Hepatitis B viral genome in preclinical models.Cell death & disease · 2021Article
- Targeting the Ubiquitin-Proteasome System for Cancer Therapeutics by Small-Molecule Inhibitors.Cancers · 2021Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo assess safety/tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of DEBIO1143, an antagonist of inhibitor apoptosis proteins.
methodsThis first-in-man study in patients with advanced cancer used an accelerated dose titration design. DEBIO1143 was given orally once daily on days 1-5 every 2 or 3 weeks until disease progressed or patients dropped out. The starting dose of 5 mg was escalated by 100% in single patients until related grade 2 toxicity occurred. This triggered expansion to cohorts of three and subsequently six patients and reduction in dose increments to 50%. Maximum tolerated dose (MTD) was exceeded when any two patients within the same cohort experienced dose-limiting toxicity (DLT). On days 1 and 5, PK and PD samples were taken.
resultsThirty-one patients received doses from 5 to 900 mg. Only one DLT was reported at 180 mg. No MTD was found. Most common adverse drug reactions were fatigue (26%), nausea (23%), and vomiting (13%). Average t max and T 1/2 was about 1 and 6 h, respectively. Exposure increased proportionally with doses from 80 to 900 mg, without accumulation over 5 days. Plasma CCL2 increased at 3-6 h postdose and epithelial apoptosis marker M30 on day 5; cIAP-1 levels in PBMCs decreased at all doses >80 mg. Five patients (17%) had stable disease as the best treatment response.
conclusionDEBIO1143 was well tolerated at doses up to 900 mg and elicited PD effects at doses greater 80 mg. Limited antitumor activity may suggest development rather as adjunct treatment.
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