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

Sep 23, 2026

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Patients with recurrent endometrial or ovarian cancer face poor survival outcomes. This phase Ib trial evaluated copanlisib, a PI3K inhibitor, combined with niraparib, a PARP inhibitor, assessing clinical efficacy, toxicity, and translational biomarkers. Thirty patients were enrolled; an RP2D was not established due to dose-limiting toxicities, including grade 3 maculopapular rash. Objective response rate was 12.5%. RPPA proteomics suggested downstream PI3K/Akt signaling and candidate biomarkers to guide future combination strategies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Purpose

Patients and Methods

Results

Conclusions

Introduction

Combination Therapy with Copanlisib and Niraparib in Patients with Recurrent Endometrial and Ovarian Cancer (COPANIRA): Efficacy, Toxicity, and Translational Insights Allison L. Brodsky1, Amma Asare1, Bryan Fellman2, Kristin Anderson1, Jun Yao3, Sanghoon Lee1, Hai Tran4, Xun Xu2, Jinsong Liu5, Joseph Celestino1, Richard A. Hajek1, Margaret B. Morgan5, Mohammad Mohammad6, Pamela Soliman1, Aaron Shafer1, Anil K. Sood1, Diane Bodurka1, Nicole D. Fleming1, Michaela Onstad Grinsfelder1, Ljiljana Milojevic1, Amir A. Jazaeri1, Gordon B. Mills7, Robert L. Coleman8, and Shannon N. Westin1 | | | A | | B | S | | T | R | | A | | C | T | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Purpose: 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.
Patients and Methods: 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.
􀀶 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Results: 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.
Conclusions: The combination of copanlisib and niraparib demonstrated limited tolerability, and the ORR was modest. However, functional proteomic analyses identified candidate biomarkers—particularly Akt pathway substrates—which may inform future strategies to optimize PI3K and PARPi combinations. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Introduction Ovarian cancer (encompassing ovarian, fallopian tube, and primary peritoneal cancers) has been the deadliest gynecologic malignancy in the United States for decades (1). Although patients with ovarian cancer often achieve remission with initial treatment of cytoreductive surgery followed by platinum- and taxane-based chemotherapy, most patients will relapse and eventually die of their disease (2) . The proportion of deaths relati

FAQs

What was the main objective of the phase Ib trial?

The primary objective was to determine the recommended phase II dose (RP2D) of copanlisib plus niraparib based on dose-limiting toxicity over a 28-day window.

What were the key findings regarding tolerability and response?

An RP2D was not established because of DLTs, most commonly grade 3 maculopapular rash attributed to copanlisib. The objective response rate was 12.5%.

How did the study use tumor biopsies to understand response?

Tumor biopsies were analyzed using RPPA to find molecular correlates of response. Protein expression differences and PI3K/Akt pathway substrate patterns suggested downstream PI3K signaling linked to outcomes.

Sep 23, 2026

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