Reference Detail

Ref Type

Journal Article

PMID

(39913886)

Authors

Gouda MA, Wei Z, Rodon J, Davies MA, Janku F, Gray RJ, Wang V, McShane LM, Rubinstein LV, Patton DR, Williams PM, Hamilton SR, Liu R, Bota DA, Swiecicki PL, Buchschacher GL, Tricoli JV, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT

Title

Phase II Study of Copanlisib in Patients With PTEN Loss: Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocols Z1G and Z1H.

Journal	Vol	Issue	Date	Pages	Journal Short Title
JCO precision oncology	9		2025 Feb	e2400451	JCO Precis Oncol

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Abstract Text

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.Patients with complete loss of cytoplasmic and nuclear PTEN as determined by immunohistochemistry regardless of PTEN mutation or deletion status were included in subprotocol Z1G, and patients with a deleterious mutation in the PTEN gene and retained expression of PTEN were included in subprotocol Z1H. Copanlisib was given intravenously over 1 hour at a dose of 60 mg on days 1, 8, and 15 in a 21-day-on and 7-day-off schedule in 28-day cycles. Patients continued treatment until disease progression or unacceptable toxicity.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.Our results do not support the antitumor activity of single-agent copanlisib in tumors with PTEN loss regardless of mutation or deletion status or PTEN deleterious mutations with PTEN expression.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
PTEN inact mut	Advanced Solid Tumor	no benefit	Copanlisib	Phase II	Actionable	In a Phase II trial (NCI-MATCH subprotocol Z1H), Aliqopa (copanlisib) treatment demonstrated limited efficacy in patients with advanced solid tumors harboring PTEN inactivating mutations, with an objective response rate of 3.4% (1/29, 1 partial response in a patient with endometrioid endometrial adenocarcinoma), stable disease in 28% (8/29) of patients, median progression-free survival (PFS) of 1.8 mo, 6-mo PFS rate of 15.4%, and median overall survival of 9.0 mo (PMID: 39913886; NCT02465060).	39913886
PTEN loss	Advanced Solid Tumor	no benefit	Copanlisib	Phase II	Actionable	In a Phase II trial (NCI-MATCH subprotocol Z1G), Aliqopa (copanlisib) treatment demonstrated limited efficacy in advanced solid tumor patients with PTEN loss, resulting in an objective response rate of 0% (0/20), stable disease in 35% (7/20) of patients, median progression-free survival (PFS) of 1.8 mo, 6-mo PFS rate of 17.5%, and median overall survival of 13.7 mo (PMID: 39913886; NCT02465060).	39913886

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