Copanlisib in combination with nivolumab formicrosatellite stable colorectal cancer: a phase 1/2 trial
PIK3CA is mutated in ~15% of colorectal cancers (CRC). PI3K regulates immunity, inhibition potentially enhances anti-tumor immunity. We launched a phase 1/2 trial of copanlisib (PIK3CA inhibitor) and nivolumab (anti-PD-1) in metastatic microsatellite stable CRC (NCT03711058): Cohort A: PIK3CAwt (n = 17) and Cohort B: PIK3CAmut (n = 22). Copanlisib/nivolumab is well tolerated with recommended phase 2 dose of nivolumab 480 mg day 1 and copanlisib 60 mg days 1/8/15 of a 28-day cycle. Primary endpoint of objective response rate at 6 months was not met with Cohort A: 0/17 and Cohort B: 2/22 having 6-month treatment response. Secondary endpoints are median progression-free survival (Cohort A: 1.7 months; Cohort B: 1.6 months), median overall survival (Cohort A: 8.5 months; Cohort B: 6.7 months), duration of response (Cohort A: 13.1 months; Cohort B: 17 months) and 6-month disease control rate (Cohort A: 2/17; Cohort B: 3/22). Secondary endpoints were not statistically different between these cohorts. Metastatic microsatellite-stable colorectal cancer (CRC) treated with anti–PD-1 therapy has previously not shown clinical responses. Here, the authors report a phase 1/2 trial of copanlisib in combination with the PD-1 inhibitor nivolumab for patients with metastatic microsatellite stable CRC.
Authors
- Dung T. Le (ORCID: https://orcid.org/0000-0002-2110-7697)
- Jeremiah A. Wala (ORCID: https://orcid.org/0000-0001-6591-1620)
- Kristin Qian (ORCID: https://orcid.org/0000-0002-5016-0112)
- Jeffrey A. Meyerhardt (ORCID: https://orcid.org/0000-0002-1120-0898)
- Donehower Rc
- Harshabad Singh (ORCID: https://orcid.org/0000-0001-6295-2013)
- Marios Giannakis (ORCID: https://orcid.org/0000-0001-9012-6982)
- Won Jin Ho (ORCID: https://orcid.org/0000-0003-2644-5086)
- Elizabeth M. Jaffee (ORCID: https://orcid.org/0000-0003-3841-6549)
- Natalie B. Collins (ORCID: https://orcid.org/0000-0003-2980-9244)
- Jia‐Ren Lin (ORCID: https://orcid.org/0000-0003-4702-7705)
- Benjamin L. Schlechter (ORCID: https://orcid.org/0000-0002-1529-3278)
- Peter Karl Sorger (ORCID: https://orcid.org/0000-0002-3364-1838)
- Maureen Berg
- Ewa Kulikowicz
- Yvette Cetasaan
- Christopher Jakubowski (ORCID: https://orcid.org/0000-0002-1085-2157)
- Lei Zheng (ORCID: https://orcid.org/0000-0003-4163-2541)
- Hao Wang (ORCID: https://orcid.org/0000-0001-6489-6940)
- S Taranath Chan
- Dr. Emma Johnson
- J H Lu
- Eric S. Christenson (ORCID: https://orcid.org/0000-0001-5261-6083)
- Nilofer Azad
- Ilene Browner
- Rachel Klein
- Rose Parkinson
Institutions
- Bloomberg (United States) (US)
- Harvard University (US)
- Johns Hopkins University (US)
- Johns Hopkins Medicine (US)
- Sidney Kimmel Cancer Center (US)
- Dana-Farber Cancer Institute (US)
- Center for Systems Biology (US)
- Sidney Kimmel Comprehensive Cancer Center (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-07-23
- DOI
- https://doi.org/10.1038/s41467-026-72985-6
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Conquer Cancer Foundation
- Bristol-Myers Squibb
- Bayer
- Johns Hopkins University
- Colorectal Cancer Alliance