ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
A phase I study of continuous oral dosing of OSI-906, a dual inhibitor of insulin-like growth factor-1 and insulin receptors, 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 56 papers.
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Who cites it
56 citing papers in PubMed, 95 citations in OpenAlex.
- Linsitinib (OSI-906) for the Treatment of Adult and Pediatric Wild-Type Gastrointestinal Stromal Tumors, a SARC Phase II Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- 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
- Deciphering oxidative stress-related heterogeneity and developing a prognostic signature for colorectal cancer.Scientific reports · 2026Article
- The dual IGF-1R/IR blocker, Linsitinib, modulates human orbital fibroblast activity and proliferation.Frontiers in immunology · 2026Article
- Key targets for small molecule drugs on the IGF1 signaling pathway.Future medicinal chemistry · 2025Article
- Effects of linsitinib on M22 and IGF:1-treated 3D spheroids of human orbital fibroblasts.Scientific reports · 2025Article
- A Comprehensive Review of Thyroid Eye Disease Pathogenesis: From Immune Dysregulations to Novel Diagnostic and Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Systemic Management of Advanced Adrenocortical Carcinoma.Current treatment options in oncology · 2024Review
- The changing landscape of thyroid eye disease: current clinical advances and future outlook.Eye (London, England) · 2024Review
- IGF1R Contributes to Cell Proliferation inCancers · 2023Article
- Linsitinib, an IGF-1R inhibitor, attenuates disease development and progression in a model of thyroid eye disease.Frontiers in endocrinology · 2023Article
- Article
- The Insulin-like Growth Factor Signaling Pathway in Breast Cancer: An Elusive Therapeutic Target.Life (Basel, Switzerland) · 2022Review
- Computational Drug Repurposing Based on a Recommendation System and Drug-Drug Functional Pathway Similarity.Molecules (Basel, Switzerland) · 2022Article
- Overexpression of BACH1 mediated by IGF2 facilitates hepatocellular carcinoma growth and metastasis via IGF1R and PTK2.Theranostics · 2022Article
- The Intricate Crosstalk Between Insulin and Pancreatic Ductal Adenocarcinoma: A Review From Clinical to Molecular.Frontiers in cell and developmental biology · 2022Review
- IGF2 is a potential factor in RAI-refractory differentiated thyroid cancer.Oncology letters · 2021Article
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeOSI-906 is a potent inhibitor of insulin-like growth factor-1 receptor (IGF1R) and insulin receptor (IR). The purpose of this study was to determine the MTD, safety, pharmacokinetics, pharmacodynamics, and preliminary activity of OSI-906 in patients with advanced solid tumors. PATIENTS AND
methodsThis was a nonrandomized, open-label, phase I, dose-escalation study in patients with advanced solid tumors. The study also included a diabetic expansion cohort and a biomarker expansion cohort of patients with colorectal cancer. Patients were treated with OSI-906 by once- or twice-daily continuous dosing schedules.
resultsOf 95 patients enrolled in the study, 86 received at least one dose of OSI-906. Dose-limiting toxicities included QTc prolongation, grade 2 abdominal pain and nausea, hyperglycemia, and elevation of aspartate aminotransferase and alanine aminotransferase (all grade 3). The MTDs were established to be 400 mg once daily and 150 mg twice daily. The recommended phase II dose was determined as 150 mg twice daily. OSI-906 was rapidly absorbed with a half-life of 5 hours, and steady-state plasma concentrations were achieved by day 8. Pharmacodynamic effects on IGF1R and IR phosphorylation were levels observed and correlated with plasma concentrations of OSI-906. Thirty-one patients had stable disease as their best response. One patient with melanoma had a radiographic partial response and underwent resection, during which only melanocytic debris but no viable tumor tissue was identified.
conclusionsAt the established MTD, OSI-906 was well tolerated and antitumor activity was observed. These results support further evaluation of OSI-906 in solid tumors.
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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.