CTNI-63. PRELIMINARY SAFETY AND EFFICACY OF EMAVUSERTIB (CA-4948) IN COMBINATION WITH IBRUTINIB IN RELAPSED/REFRACTORY PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA PATIENTS

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.

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Publication Details

Journal
Neuro-Oncology
Published
2025-11-01
DOI
https://doi.org/10.1093/neuonc/noaf201.0559
Primary Topic
CNS Lymphoma Diagnosis and Treatment
Type
article
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article

CTNI-63. PRELIMINARY SAFETY AND EFFICACY OF EMAVUSERTIB (CA-4948) IN COMBINATION WITH IBRUTINIB IN RELAPSED/REFRACTORY PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA PATIENTS

Teresa Calimeri, Maureen Lane, Adolfo de la Fuente, Praveen Ramakrishnan Geethakumari et al.
Neuro-Oncology
CNS Lymphoma Diagnosis and Treatment
article

CTNI-63. PRELIMINARY SAFETY AND EFFICACY OF EMAVUSERTIB (CA-4948) IN COMBINATION WITH IBRUTINIB IN RELAPSED/REFRACTORY PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA PATIENTS

Teresa Calimeri, Maureen Lane, Adolfo de la Fuente, Praveen Ramakrishnan Geethakumari, Luca Nassi, Amrita Chauhan, Christian Grommes, David Lavie, Alessia Castellino, Benvenuto Ferrari, Han W. Tun, Muhamad Alhaj Moustafa, Michał Taszner, Laurence Schenone, Grzegorz S. Nowakowski, Francisco J. Hernandez‐Ilizaliturri, Lakshmi Nayak, Wanying Zhao, Christopher R D’Angelo, Anna Dąbrowska‐Iwanicka, Anna Schmitt, Li Zhou, Caroline Houillier, Andrés J.M. Ferreri, Itai Levi, Julie Vose
article en

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.

Neuro-OncologyVol. 27(Supplement_5)
Roswell Park Comprehensive Cancer Center (US), Mayo Clinic (US), Memorial Sloan Kettering Cancer Center (US), The University of Texas MD Anderson Cancer Center (US), Vita-Salute San Raffaele University (IT), Hadassah Medical Center (IL), Soroka Medical Center (IL), Jacksonville College (US), Sorbonne Université (FR), Southwestern Medical Center (US), Azienda Ospedaliero-Universitaria Careggi (IT), Dana-Farber Cancer Institute (US), National Institute of Oncology (HU), Pitié-Salpêtrière Hospital (FR), Mayo Clinic in Arizona (US), Curis (United States) (US), Institut Bergonié (FR), Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo (IT), Mayo Clinic in Florida (US), The Maria Sklodowska-Curie National Research Institute of Oncology (PL), Istituti di Ricovero e Cura a Carattere Scientifico (IT), MD Anderson Cancer Center Madrid (ES), Hôpital de la Timone (FR), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT), University of Florence (IT), University of Nebraska Medical Center (US), Gdańsk Medical University (PL), The University of Texas Southwestern Medical Center (US)
Openalex Percentile: Top 53%
CNS Lymphoma Diagnosis and Treatment
DOIOpen Access PDFOpenAlex
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