Phase Ii Study Of Pi3k Inhibitor Copanlisib In Cancer Patients With Deleterious Pten Mutations And Retained Pten Protein Expression: Results From The Nci-Match Trial (Eay131) Sub-Protocol Z1h

The NCI-MATCH trial, the largest national study (1173 sites) for patients with relapsed/refractory solid tumors, lymphomas and myeloma, assigns targeted therapies based on individual tumor molecular alterations detected using clinical targeted next-generation sequencing and immunohistochemistry. It was hypothesized that patients with deleterious PTEN mutations without PTEN protein loss may benefit from treatment with the pan-PI3K inhibitor copanlisib. Eligibility included patients who had relapsed/refractory cancers, adequate end-organ function, and ECOG PS ≤1 with presence of deleterious PTEN mutations without loss of expression in tumor tested in an approved CLIA-compliant laboratory. Patients received copanlisib 60 mg IV on days 1, 8 and 15 of 28-days cycles until disease progression or unacceptable toxicity. RECIST 1.1 overall response rate was the primary endpoint. Of 35 enrolled patients, 33 received treatment (10 uterine cancer, 8 glioblastoma, 2 breast cancer, 13 other cancers). At the time of data cut-off (4/12/2021), 33 patients discontinued treatment (30 due to progression, 1 due to adverse event, 1 withdrew consent and 1 patient died). One patient (3%) with uterine endometrial adenocarcinoma (PTEN and TP53 mutations) achieved a partial response (-100% with persistence of non-target lesions). Of 9 (27%) patients with stable disease (SD), 4 had SD > 168 days (squamous cell lung cancer; adenocarcinoma of unknown primary, breast cancer, salivary gland cancer). Median progression-free survival was 1.8 months. Most frequent ≥ grade (G) 3 treatment-related adverse events (TRAE) included G3 hypertension (n=6), G3 nausea (n=3), G3 fatigue (n=3) and G3 maculo-papular rash (n=3). Most frequent TRAE of any grade included nausea (n=18), fatigue (n=14) and hyperglycemia (n=11). Results of arm Z1H of the NCI-MATCH trial demonstrated that single agent copanlisib has limited activity in cancers with deleterious PTEN mutation without loss of expression.