Abstract 530P
Background
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.
Methods
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.
Results
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).
Conclusions
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.
Clinical trial identification
NCT02465060.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
National Cancer Institute of the National Institutes of Health.
Disclosure
F. Janku: Financial Interests, Institutional, Funding: Agios; Financial Interests, Institutional, Funding: Asana; Financial Interests, Institutional, Funding: Astellas; Financial Interests, Institutional, Funding: Astex; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: Bicara; Financial Interests, Institutional, Funding: BioMed Valley Discoveries; Financial Interests, Institutional, Funding: Bioxcel; Financial Interests, Institutional, Funding: Bristol-Myers Squibb; Financial Interests, Institutional, Funding: Deciphera; Financial Interests, Institutional, Funding: FujiFilm Pharma; Financial Interests, Institutional, Funding: Genentech; Financial Interests, Institutional, Funding: Ideaya; Financial Interests, Institutional, Funding: JS Innopharm; Financial Interests, Institutional, Funding: Lilly; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Novellus; Financial Interests, Institutional, Funding: Plexxikon; Financial Interests, Institutional, Funding: Proximagen; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Institutional, Funding: Sotio; Financial Interests, Institutional, Funding: SpringBank; Financial Interests, Institutional, Funding: SQZ Biotechnologies; Financial Interests, Institutional, Funding: Synlogic; Financial Interests, Institutional, Funding: Synthorx; Financial Interests, Institutional, Funding: Symphogen; Financial Interests, Personal, Full or part-time Employment, Consultant: Asana; Financial Interests, Personal, Full or part-time Employment, Consultant: Baush Health; Financial Interests, Personal, Full or part-time Employment, Consultant: Cardiff Oncology; Financial Interests, Personal, Full or part-time Employment, Consultant: Deciphera; Financial Interests, Personal, Full or part-time Employment, Consultant: Guardant Health; Financial Interests, Personal, Full or part-time Employment, Consultant: Ideaya; Financial Interests, Personal, Full or part-time Employment, Consultant: IFM Therapeutics; Financial Interests, Personal, Full or part-time Employment, Consultant: Immunomet; Financial Interests, Personal, Full or part-time Employment, Consultant: Illumina; Financial Interests, Personal, Full or part-time Employment, Consultant: Jazz Pharmaceuticals; Financial Interests, Personal, Full or part-time Employment, Consultant: Novartis; Financial Interests, Personal, Full or part-time Employment, Consultant: PureTech Health; Financial Interests, Personal, Full or part-time Employment, Consultant: Sotio; Financial Interests, Personal, Full or part-time Employment, Consultant: Synlogic; Financial Interests, Personal, Ownership Interest: Cardiff Oncology; Financial Interests, Personal, Other: Bio-Rad; Financial Interests, Personal, Other: Biocartis. All other authors have declared no conflicts of interest.