PURPOSE: Copanlisib, a pan-class phosphatidylinositol 3-kinase (PI3K) inhibitor with activity predominantly against the PI3K-delta and PI3K-alpha isoforms, has shown promising results in preclinical cancer models with PTEN loss. Herein, we report the activity and safety data from the Z1G and Z1H subprotocols, which included patients with PTEN loss, of the National Cancer Institute Molecular Analysis for Therapy Choice trial. METHODS: Patients with complete loss of cytoplasmic and nuclear PTEN as determined by immunohistochemistry regardless of RESULTS: Overall, 49 patients (20 patients in Z1G and 29 in Z1H) were included in the primary efficacy analyses. The objective response rates in both cohorts were 0% (Z1G
90% CI, 0 to 13.9) and 3.4% (Z1H
90% CI, 0.2 to 15.3), respectively. The median progression-free and overall survival durations were 1.8 months (90% CI, 1.4 to 3.9 months) and 13.7 months (90% CI, 6.8 to 18.3 months) for the Z1G cohort and 1.8 months (90% CI, 1.8 to 2.1 months) and 9.0 months (90% CI, 5.4 to 13.3 months) for the Z1H cohort, respectively. CONCLUSION: Our results do not support the antitumor activity of single-agent copanlisib in tumors with PTEN loss regardless of mutation or deletion status or