ArticleInvestigational new drugs2016
A first-in-human dose-escalation study of the oral proteasome inhibitor oprozomib in patients with advanced solid tumors.
Article in Investigational new drugs, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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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
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Efficacy and safety results from a phase 1b/2, multicenter, open-label study of oprozomib and dexamethasone in patients with relapsed and/or refractory multiple myeloma.Leukemia research · 2019Trial
- Pharmacokinetics, Target Engagement of an Immunoproteasome Subunit Low-Molecular-Mass Polypeptide‑2 (LMP2) Inhibitor AR-01, and Its Anti-Alzheimer's Effects in Rodents.ACS pharmacology & translational science · 2026Article
- Marizomib in the therapy of brain tumors-how far did we go and where do we stand?Pharmacological reports : PR · 2025Review
- The role of the unfolded protein response pathway in bone homeostasis and potential therapeutic target in cancer-associated bone disease.Bone research · 2025Review
- Oncogenic stress response mechanisms as new therapeutic targets in cancer treatment: A review.Medicine · 2025Review
- Ubiquitin proteasome system (UPS): a crucial determinant of the epigenetic landscape in cancer.Epigenomics · 2025Review
- Identification of Malaria-Selective Proteasome β5 Inhibitors Through Pharmacophore Modeling, Molecular Docking, and Molecular Dynamics Simulation.International journal of molecular sciences · 2024Article
- Bortezomib Pharmacogenetic Biomarkers for the Treatment of Multiple Myeloma: Review and Future Perspectives.Journal of personalized medicine · 2023Review
- A Reliable and Effective UPLC-MS/MS Method for the Determination of Oprozomib in Rat Plasma.Journal of analytical methods in chemistry · 2023Article
- Proteasome regulators in pancreatic cancer.World journal of gastrointestinal oncology · 2022Review
- Combined treatment of marizomib and cisplatin modulates cervical cancer growth and invasion and enhances antitumor potentialFrontiers in oncology · 2022Article
- Proteasome Inhibitors and Their Pharmacokinetics, Pharmacodynamics, and Metabolism.International journal of molecular sciences · 2021Review
- Oral Proteasomal Inhibitors Ixazomib, Oprozomib, and Delanzomib Upregulate the Function of Organic Anion Transporter 3 (OAT3): Implications in OAT3-Mediated Drug-Drug Interactions.Pharmaceutics · 2021Article
- Proteasome Inhibitor-Related Cardiotoxicity: Mechanisms, Diagnosis, and Management.Current oncology reports · 2020Review
- Proteasome Inhibitors: Harnessing Proteostasis to Combat Disease.Molecules (Basel, Switzerland) · 2020Review
- Pharmacodynamics and pharmacokinetics of proteasome inhibitors for the treatment of multiple myeloma.Expert opinion on drug metabolism & toxicology · 2019Review
- Development of Novel Epoxyketone-Based Proteasome Inhibitors as a Strategy To Overcome Cancer Resistance to Carfilzomib and Bortezomib.Journal of medicinal chemistry · 2019Article
- Physiologically-based pharmacokinetic modelling to predict oprozomib CYP3A drug-drug interaction potential in patients with advanced malignancies.British journal of clinical pharmacology · 2019Article
- Cardiovascular adverse events in multiple myeloma patients.Journal of thoracic disease · 2018Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo determine the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), safety, and pharmacokinetic and pharmacodynamic profiles of the tripeptide epoxyketone proteasome inhibitor oprozomib in patients with advanced refractory or recurrent solid tumors.
methodsPatients received escalating once daily (QD) or split doses of oprozomib on days 1-5 of 14-day cycles (C). The split-dose arm was implemented and compared in fasted (C1) and fed (C2) states. Pharmacokinetic samples were collected during C1 and C2. Proteasome inhibition was evaluated in red blood cells and peripheral blood mononuclear cells.
resultsForty-four patients (QD, n = 25; split dose, n = 19) were enrolled. The most common primary tumor types were non-small cell lung cancer (18%) and colorectal cancer (16%). In the 180-mg QD cohort, two patients experienced DLTs: grade 3 vomiting and dehydration; grade 3 hypophosphatemia (n = 1 each). In the split-dose group, three DLTs were observed (180-mg cohort: grade 3 hypophosphatemia; 210-mg cohort: grade 5 gastrointestinal hemorrhage and grade 3 hallucinations (n = 1 each). In the QD and split-dose groups, the MTD was 150 and 180 mg, respectively. Common adverse events (all grades) included nausea (91%), vomiting (86%), and diarrhea (61%). Peak concentrations and total exposure of oprozomib generally increased with the increasing dose. Oprozomib induced dose-dependent proteasome inhibition. Best response was stable disease.
conclusionsWhile generally low-grade, clinically relevant gastrointestinal toxicities occurred frequently with this oprozomib formulation. Despite dose-dependent increases in pharmacokinetics and pharmacodynamics, single-agent oprozomib had minimal antitumor activity in this patient population with advanced solid tumors.
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Registered trials
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