ArticleInvestigational new drugs2016
A phase I trial of ANG1/2-Tie2 inhibitor trebaninib (AMG386) and temsirolimus in advanced solid tumors (PJC008/NCI♯9041).
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 11 papers.
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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
11 citing papers in PubMed, 19 citations in OpenAlex.
- Recent Advances with Precision Medicine Treatment for Breast Cancer including Triple-Negative Sub-Type.Cancers · 2023Review
- Macrophage-derived SHP-2 inhibits the metastasis of colorectal cancer via Tie2-PI3K signals.Oncology research · 2023Article
- The roles of metabolic profiles and intracellular signaling pathways of tumor microenvironment cells in angiogenesis of solid tumors.Cell communication and signaling : CCS · 2022Review
- Macrophage-Targeted Therapy Unlocks Antitumoral Cross-talk between IFNγ-Secreting Lymphocytes and IL12-Producing Dendritic Cells.Cancer immunology research · 2022Article
- Targeted therapies in gynecological cancers: a comprehensive review of clinical evidence.Signal transduction and targeted therapy · 2020Review
- Activation of the IGF Axis in Thyroid Cancer: Implications for Tumorigenesis and Treatment.International journal of molecular sciences · 2019Review
- Targeting Receptor Kinases in Colorectal Cancer.Cancers · 2019Review
- Clinical Stratification of High-Grade Ovarian Serous Carcinoma Using a Panel of Six Biomarkers.Journal of clinical medicine · 2019Article
- Precision medicine based on tumorigenic signaling pathways for triple-negative breast cancer.Oncology letters · 2018Review
- Ang-2 but not Ang-1 expression in perivascular soft tissue tumors.Journal of orthopaedics · 2017Article
- Hemostatic Changes Associated With Increased Mortality Rates in Hospitalized Patients With HIV-Associated Tuberculosis: A Prospective Cohort Study.The Journal of infectious diseases · 2017Observational
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundThere is crosstalk between the ANG-Tie2 and the PI3K/Akt/mTOR pathways. Combined ANG1/2 and mTOR blockade may have additive anti-cancer activity. The combination of trebananib, an inhibitor of ANG1/2-Tie2 interaction, with temsirolimus was evaluated in patients with advanced solid tumors to determine tolerability, maximum tolerated dose (MTD), and preliminary antitumor activity.
methodsPatients were enrolled using 3 + 3 design, and were given intravenous trebananib and temsirolimus on Day 1, 8, 15 and 22 of a 28-day cycle. Dose limiting toxicities (DLTs) were evaluated during cycle 1. Peripheral blood was collected for evaluation of Tie2-expressing monocytes (TEMs) and thymidine phosphorylase (TP). Sparse pharmacokinetic (PK) sampling for trebananib drug levels was performed on Day 1 and 8 of cycle 2.
resultsTwenty-one patients were enrolled, 6 at dose level (DL) 1, 7 at DL -1, and 8 at DL -2. No effect of temsirolimus on trebananib PK was observed. The most common treatment-related adverse events (AEs) were: fatigue (81 %), edema (62 %), anorexia (57 %), nausea (52 %), rash (43 %) and mucositis (43 %). The most common grade ≥ 3 AEs included lymphopenia (28 %) and fatigue (28 %). The MTD was exceeded at DL-2. Of 18 response evaluable patients, 1 partial response was observed (ER+/HER2-/PIK3CA mutant breast cancer) and 4 patients had prolonged SD ≥ 24 weeks. No correlation with clinical benefit was observed with change in number TEMs or TP expression in TEMs with treatment.
conclusionsThe MTD was exceeded at trebananib 10 mg/kg weekly and temsirolimus 20 mg weekly, with frequent overlapping toxicities including fatigue, edema, and anorexia.
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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.