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Copanlisib in combination with nivolumab formicrosatellite stable colorectal cancer: a phase 1/2 trial

Eric S Christenson1,2,3, Jeremiah A Wala4,5,6, Rose Parkinson1,2,3

  • 1Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Nature Communications
|July 23, 2026
PubMed

Insights

This study investigated copanlisib and nivolumab for metastatic colorectal cancer (CRC). The combination was well-tolerated but did not meet primary response rate goals in PIK3CA-mutated or wild-type CRC patients.

Area of Science:

  • Oncology
  • Cancer Immunology
  • Pharmacology

Background:

  • PIK3CA mutations are present in approximately 15% of colorectal cancers (CRC).
  • PI3K signaling pathways influence anti-tumor immunity, suggesting PI3K inhibition could enhance immune responses.
  • Targeting PI3K is a potential strategy to improve outcomes in CRC.

Purpose of the Study:

  • To evaluate the safety and efficacy of combining copanlisib (a PI3K inhibitor) with nivolumab (an anti-PD-1 antibody) in patients with metastatic microsatellite stable colorectal cancer.
  • To assess the objective response rate at 6 months as the primary endpoint.
  • To explore secondary endpoints including progression-free survival, overall survival, and duration of response.

Main Methods:

  • A Phase 1/2 clinical trial (NCT03711058) was conducted.
  • Patients were divided into two cohorts: Cohort A (PIK3CA wild-type, n=17) and Cohort B (PIK3CA-mutated, n=22).
  • The recommended Phase 2 dose was determined as nivolumab 480 mg on day 1 and copanlisib 60 mg on days 1, 8, and 15 of a 28-day cycle.

Main Results:

  • The combination therapy was well-tolerated.
  • The primary endpoint of objective response rate at 6 months was not met: 0/17 in Cohort A and 2/22 in Cohort B responded.
  • Secondary endpoints, including median progression-free survival and overall survival, showed no statistically significant differences between the PIK3CA wild-type and mutated cohorts.

Conclusions:

  • Copanlisib in combination with nivolumab is a tolerable regimen for metastatic microsatellite stable colorectal cancer.
  • The combination did not demonstrate significant anti-tumor activity based on the primary endpoint of objective response rate at 6 months.
  • Further investigation may be needed to identify patient populations or treatment strategies where PI3K inhibition can enhance anti-PD-1 therapy efficacy in CRC.

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