An open-label, dose-escalation study to evaluate the safety and pharmacokinetics of CEP-9722 (a PARP-1 and PARP-2 inhibitor) in combination with gemcitabine and cisplatin in patients with advanced solid tumors

Anti-cancer Drugs
Ahmad AwadaJean-Charles Soria

Abstract

Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors may potentiate chemotherapy by hindering DNA damage repair pathways. CEP-9722 is the prodrug of CEP-8983, a selective inhibitor of PARP-1 and PARP-2. Preclinical studies and a prior phase 1 study suggested that CEP-9722 may cause less myelosuppression than has been observed with other oral PARP inhibitors. The primary objective of this study was to determine the maximum-tolerated dose of CEP-9722 in combination with gemcitabine and cisplatin in patients with advanced solid tumors. All patients received cisplatin 75 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1 and 8 of a 21-day cycle. Patients who completed one cycle of chemotherapy alone continued chemotherapy in combination with CEP-9722 150, 200, 300, or 400 mg orally twice daily on days 2-7, with dose-limiting toxicity assessed in cycle 2. Patients experiencing clinical benefit could continue treatment until disease progression or unacceptable toxicity. Thirty-two patients enrolled; 18 patients completed cycle 1 and received chemotherapy plus CEP-9722. The median (range) treatment administration with CEP-9722 was five (1-12) cycles. No patient experienced dose-limiting toxicity with CEP-9722 treatment. Grade 3/4 h...Continue Reading

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Citations

Nov 15, 2016·Expert Opinion on Therapeutic Patents·Zigao YuanYuyang Jiang
Sep 17, 2020·International Journal of Molecular Sciences·Samuele LodovichiAlvaro Galli
Mar 30, 2018·Molecular Cancer Research : MCR·Steven T SizemoreFen Xia
Dec 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Miguel Angel Galván MoralesLuis M Teran
Sep 7, 2020·Cancer Treatment Reviews·Laura CarrassaFrancesco Bertoni
Jun 1, 2021·Signal Transduction and Targeted Therapy·Lei ZhongShengyong Yang

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NCT01345357
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NCT02163694
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Software Mentioned

WinNonlin

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