Ctni-63. Preliminary Safety and Efficacy of Emavusertib (ca-4948) in Combination With Ibrutinib in Relapsed/refractory Primary Central Nervous System Lymphoma Patients
Year: 2025
Type: conference-abstract
Abstract: There are no approved treatments for relapsed/refractory (R/R) PCNSL. We show promising efficacy in the salvage setting using emavusertib in combination with ibrutinib, which targets the BCR and TLR pathways. These 2 major pathways are associated with activation of NF-κB. Updated safety and efficacy data of this combination in R/R PCNSL from the ongoing Phase 1/2 TakeAim Lymphoma trial (NCT03328078) will be presented. As of 01 May 2025, 33 patients with R/R PCNSL were treated with emavusertib in combination with ibrutinib. Eligible patients receive emavusertib in combination with ibrutinib until tumor progression or unacceptable toxicity. Median age was 63 years (range 43-81); 16 patients were male. Median prior anti-cancer therapy was 2 (range 1-5); 26 (78.8%) patients had prior BTKi exposure. Median duration of emavusertib/ibrutinib treatment was 51 days (range 5-798). Grade ≥ 3 treatment-related adverse events (TRAEs) were reported in 11 (33.3%) patients; neutropenia in 5 (15.2%) patients, amylase increased, lipase increased, and leukopenia in 2 (6.1%) patients each. The majority of Grade ≥ 3 TRAEs were reversible and manageable. Among the 19 BTKi-experienced patients treated for ≥ 28 days, there were 5 CRs and 2 PRs, with an ORR of 36.8%. Three patients with CR were on treatment for 10+ mos, with 1 CR patient ongoing with DOT of 26.2+ mos. Among the 5 BTKi-naïve patients treated for ≥ 28 days, 1 achieved CR and 3 had PR, with ORR of 80%; the CR patient is ongoing with DOT of 18.1+ mos. The ORR in the combined population was 45.8% (6 CRs; 5 PRs). The combination of emavusertib and ibrutinib demonstrates promising clinical activity and an acceptable safety profile in patients with R/R PCNSL. This regimen appears capable of overcoming resistance to prior BTKi therapy. Patient enrollment in this trial continues.
Source: Neuro-Oncology
Authors: Lakshmi Nayak, MD, Anna Dabrowska-Iwanicka, MD, Han W Tun, MD, Muhamad Alhaj Moustafa, MD, MS, Grzegorz Nowakowski, MD, Adolfo De La Fuente, MD, Itai Levi, MD, Christian Grommes, MD, David Lavie, MD, Alessia Castellino, MD, Michael Taszner, MD, Praveen Ramakrishnan Geethakumari, MD, MS, MBA, Laurence Schenone, MD, Andrés J M Ferreri, MD, Teresa Calimeri, MD, Luca Nassi, MD, Caroline Houillier, MD, Anna Schmitt, MD, Francisco J Hernandez-Ilizaliturri, MD, Ayushi Chauhan, MD, Maureen E Lane, PhD, Li Zhou, PhD, Wanying Zhao, PhD, Dora Ferrari, BS, Julie M Vose, MD, MBA, Christopher R D’Angelo, MD
Institutions: Dana-Farber Cancer Institute, The Maria Sklodowska-Curie National Research Institute of Oncology, Mayo Clinic in Florida, Mayo Clinic Comprehensive Cancer Center (Florida), Mayo Clinic, MD Anderson Cancer Center Madrid, Soroka Medical Center, Memorial Sloan Kettering Cancer Center, Hadassah Medical Center, Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo, Gdańsk Medical University, Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Hôpital de la Timone, IRCCS Ospedale San Raffaele, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Sorbonne Université, Pitié-Salpêtrière Hospital, Institut du Cerveau, Institut Bergonié, Roswell Park Comprehensive Cancer Center, The University of Texas MD Anderson Cancer Center, Curis (United States), University of Nebraska Medical Center
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416140287
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