ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
Phase I study of intermittent oral dosing of the insulin-like growth factor-1 and insulin receptors inhibitor OSI-906 in patients with advanced solid tumors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 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
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- New insights on the cardiovascular effects of IGF-1.Frontiers in endocrinology · 2023Pooled it
- A phase 2 study of OSI-906 (linsitinib, an insulin-like growth factor receptor-1 inhibitor) in patients with asymptomatic or mildly symptomatic (non-opioid requiring) metastatic castrate resistant prostate cancer (CRPC).Investigational new drugs · 2018Trial
- Randomised Phase 2 study of maintenance linsitinib (OSI-906) in combination with erlotinib compared with placebo plus erlotinib after platinum-based chemotherapy in patients with advanced non-small cell lung cancer.British journal of cancer · 2017Trial
- Phase 2 Study of Erlotinib in Combination With Linsitinib (OSI-906) or Placebo in Chemotherapy-Naive Patients With Non-Small-Cell Lung Cancer and Activating Epidermal Growth Factor Receptor Mutations.Clinical lung cancer · 2017Trial
- The dual IGF-1R/IR blocker, Linsitinib, modulates human orbital fibroblast activity and proliferation.Frontiers in immunology · 2026Article
- Coordinated regulation of IGF1R by HIF1α and HIF2α enhances chemoresistance in glioblastoma.Frontiers in pharmacology · 2025Article
- Amino Acid Biosynthesis Inhibitors in Tuberculosis Drug Discovery.Pharmaceutics · 2024Review
- Shifting from a Biological-Agnostic Approach to a Molecular-Driven Strategy in Rare Cancers: Ewing Sarcoma Archetype.Biomedicines · 2023Review
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- Targeted Therapy for Adrenocortical Carcinoma: A Genomic-Based Search for Available and Emerging Options.Cancers · 2022Article
- Computational Drug Repurposing Based on a Recommendation System and Drug-Drug Functional Pathway Similarity.Molecules (Basel, Switzerland) · 2022Article
- The Intricate Crosstalk Between Insulin and Pancreatic Ductal Adenocarcinoma: A Review From Clinical to Molecular.Frontiers in cell and developmental biology · 2022Review
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- IGF1 receptor inhibition amplifies the effects of cancer drugs by autophagy and immune-dependent mechanisms.Journal for immunotherapy of cancer · 2021Article
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- Oncogenic State and Cell Identity Combinatorially Dictate the Susceptibility of Cells within Glioma Development Hierarchy to IGF1R Targeting.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- Wnt/β-catenin activation cooperates with loss of p53 to cause adrenocortical carcinoma in mice.Oncogene · 2020Article
- Review
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12 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeWe determined the maximum tolerated dose (MTD), safety, pharmacokinetics, pharmacodynamics, and preliminary activity of OSI-906, a potent, oral, dual inhibitor of insulin-like growth factor-1 receptor (IGF1R) and insulin receptor (IR), in patients with advanced solid tumors. EXPERIMENTAL
designThis was a multicenter, open-label, dose escalation phase I study evaluating three intermittent dosing schedules of once-daily OSI-906 [schedule (S) 1, days 1-3 every 14 days; S2, days 1-5 every 14 days; S3, days 1-7 every 14 days]. A fed-fasting expansion cohort was included in the study.
resultsSeventy-nine patients were enrolled: 62 in S1, 4 in S2, and 13 in S3. S2 was discontinued. Dose-limiting toxicity comprised grade 3-4 hyperglycemia, vomiting, fatigue, and prolonged QTc interval. The MTD and recommended phase II dose of OSI-906 was 600 mg for both S1 and S3 schedules. Other common adverse events were grade 1-2 nausea, vomiting, fatigue, and diarrhea. The pharmacokinetics of OSI-906 was dose linear, and the terminal half-life ranged between 2 and 6 hours. High-fat meals had a moderate effect on the pharmacokinetics of OSI-906. At the MTD, inhibition of IGF1R and IR was observed in peripheral blood mononuclear cells. An increase in plasma IGF1 concentrations, an indirect measure of IGF1R signaling inhibition, was seen at doses ≥ 450 mg. Two patients with adrenocortical carcinoma achieved partial responses.
conclusionThe MTD of 600 mg was well tolerated and associated with preliminary antitumor activity. These data support further evaluation of OSI-906 in solid tumors.
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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.