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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)

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Summary

Background The inhibition of insulin-like growth factor receptor-1 (IGF-1R) induces cell cycle arrest and enhancing the effect of castration by delay of progression of human prostate cancer models. Linsitinib is a small molecule and potent dual inhibitor of IGF-1R and insulin receptor tyrosine kinase activity. We report results of a single-arm, phase II study evaluating the safety and efficacy of linsitinib in men with chemotherapy-naïve asymptomatic or mildly symptomatic metastatic castration resistant prostate cancer (mCRPC). Methods Patients received at 150 mg orally twice daily on a 28-day cycle. The primary endpoint was prostate specific (PSA) response at 12 weeks and correlative studies included circulating tumor cells (CTCs) and circulating endothelial cells (CECs). Results Seventeen patients, median age 68 (55–78) and pre-treatment PSA of 55.23 (2.46–277.60) were enrolled and completed 12 weeks of therapy. All but two patients discontinued therapy secondary to PSA progression, which met the predefined futility criteria and led to early termination of this study. Overall best response (RECIST v1.1) included a partial response in 1 patient and stable disease in 8 patients. Higher baseline CTCs were associated with higher pre-treatment PSA levels (Spearman r = 0.49, p = 0.04) but no correlation between PSA progression and CTCs/CECs were observed. Most common adverse events included fatigue, nausea/vomiting, AST/ALT changes and prolonged QT interval. Conclusions Single-agent linsitinib was safe and well tolerated but failed to show activity in men with mCRPC. These results highlight the complexity of using IGF-1R as a therapeutic target in this patient population. ClinicalTrials.gov NCT01533246.

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Funding

No funding was used for this study. This was the Cancer Therapy Evaluation Program (CTEP) Sponsored Trial.

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Authors and Affiliations

  1. Case Comprehensive Cancer Center, Cleveland Clinic Taussig Cancer Institute, 9500 Euclid Ave/CA60, Cleveland, OH, 44195, USA

    Pedro Barata, Allison Tyler & Jorge A. Garcia

  2. Seidman Cancer Center, University Hospitals, Case Comprehensive Cancer Center, Cleveland, OH, USA

    Matthew Cooney

  3. Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA

    John Wright

  4. Division Hematology/Oncology, University of Virginia School of Medicine, Charlottesville, VA, USA

    Robert Dreicer

  5. Glickman Urological and Kidney Institute, Cleveland Clinic, Rockville, MD, USA

    Jorge A. Garcia

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  1. Pedro Barata
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Barata, P., Cooney, M., Tyler, A. et al. 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). Invest New Drugs 36, 451–457 (2018). https://doi.org/10.1007/s10637-018-0574-0

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