Data from Combination Therapy with Copanlisib and Niraparib in Patients with Recurrent Endometrial and Ovarian Cancer (COPANIRA): Efficacy, Toxicity, and Translational Insights

作者：Allison L. Brodsky, Amma Asare, Bryan Fellman, Kristin Anderson, Jun Yao, Sanghoon Lee, Hai Tran, Xun Xu, Jinsong Liu, Joseph Celestino, Richard A. Hajek, Margaret B. Morgan, Mohammad Mohammad, Pamela Soliman, Aaron Shafer, Anil K. Sood, Diane Bodurka, Nicole D. Fleming, Michaela Onstad Grinsfelder, Ljiljana Milojevic, Amir A. Jazaeri, Gordon B. Mills, Robert L. Coleman, Shannon N. Westin · 年份：2026 · DOI：10.1158/1078-0432.c.8395744 · 研究领域：Ovarian cancer diagnosis and treatment、Endometrial and Cervical Cancer Treatments、PARP inhibition in cancer therapy

<div>AbstractPurpose:<p>Patients with recurrent endometrial or ovarian cancer have poor survival outcomes. We evaluated the clinical efficacy and toxicity of copanlisib [a phosphatidylinositol 3-kinase (PI3K) inhibitor] and niraparib [a poly (ADP-ribose) polymerase inhibitor (PARPi)] in this patient population with translational insights.</p>Patients and Methods:<p>This was a phase Ib trial. Copanlisib was administered intravenously on days 1, 8, and 15 of a 28-day cycle, and niraparib was given orally once daily. Four dose levels were explored over a dose-limiting toxicity (DLT) window of 28 days. The primary objective was to determine the recommended phase II dose (RP2D) of this combination. Secondary objectives included safety, objective response rate (ORR), and pharmacokinetics. Tumor biopsies were analyzed using reverse phase protein array (RPPA) to identify molecular correlates of response.</p>Results:<p>Thirty patients were enrolled. An RP2D was not established due to DLTs, most commonly a grade 3 maculopapular rash attributed to copanlisib. The ORR was 12.5% (95% confidence interval, 2.8%–33.6%). RPPA was performed on tumors from eight patients. PI3K pathway activity did not correlate with PI3K mutational status. Nineteen proteins were differentially expressed between patients with stable disease and those with progressive disease; many were substrates of Akt (protein kinase B), implicating downstream PI3K signaling in response.<...