American Association for Cancer Research
Browse
15357163mct190466-sup-221632_3_supp_5798045_pydtgj.pdf (110.27 kB)

Table S1 from On-Target Pharmacodynamic Activity of the PI3K Inhibitor Copanlisib in Paired Biopsies from Patients with Malignant Lymphoma and Advanced Solid Tumors

Download (110.27 kB)
journal contribution
posted on 2023-04-03, 18:04 authored by Franck Morschhauser, Jean-Pascal Machiels, Gilles Salles, Sylvie Rottey, Simon A.J. Rule, David Cunningham, Frederic Peyrade, Christophe Fruchart, Hendrik-Tobias Arkenau, Isabelle Genvresse, Li Liu, Karl Köchert, Kui Shen, Christoph Kneip, Carol E. Peña, Joachim Grevel, Jun Zhang, Galia Cisternas, Susanne Reschke, Camille Granvil, Ahmad Awada

shows an overview of patient disposition

History

ARTICLE ABSTRACT

The PI3K inhibitor copanlisib has efficacy and manageable safety in patients with indolent lymphoma and solid tumors. Pharmacodynamic effects relative to copanlisib dose and plasma exposure were evaluated. Patients with lymphoma or solid tumors received copanlisib 0.4 or 0.8 mg/kg on days 1, 8, and 15 of a 28-day cycle. Primary variables were maximum changes in phosphorylated AKT (pAKT) levels in platelet-rich plasma (PRP) and plasma glucose. Other evaluations included PI3K signaling markers and T-lymphocytes in paired tumor biopsies, the relationship between estimated plasma exposure and pharmacodynamic markers, response, and safety. Sixty-three patients received copanlisib. PRP pAKT levels showed sustained reductions from baseline following copanlisib [median inhibition: 0.4 mg/kg, 73.8% (range −94.9 to 144.0); 0.8 mg/kg, 79.6% (range −96.0 to 408.0)]. Tumor pAKT was reduced versus baseline with copanlisib 0.8 mg/kg in paired biopsy samples (P < 0.05). Dose-related transient plasma glucose elevations were observed. Estimated copanlisib plasma exposure significantly correlated with changes in plasma pAKT and glucose metabolism markers. There were two complete responses and six partial responses; seven of eight responders received copanlisib 0.8 mg/kg. Adverse events (all grade) included hyperglycemia (52.4%), fatigue (46.0%), and hypertension (41.3%). Copanlisib demonstrated dose-dependent pharmacodynamic evidence of target engagement and PI3K pathway modulation/inhibition in tumor and immune cells. Results support the use of copanlisib 0.8 mg/kg (or flat-dose equivalent of 60 mg) in solid tumors and lymphoma, and provide a biomarker hypothesis for studies of copanlisib combined with immune checkpoint inhibitors (NCT03711058).

Usage metrics

    Molecular Cancer Therapeutics

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC