Emavusertib/Ibrutinib Combo Shows Deepening Responses in PCNSL

Updated data from the phase 1/2 TakeAim Lymphoma study (NCT03328078) showed improved objective response rates (ORRs) with emavusertib added to the Bruton tyrosine kinase inhibitor (BTKi) ibrutinib (Imbruvica) in patients with primary central nervous system lymphoma (PCNSL).¹

Updated data as of July 1, 2026, included 7 BTKi-naive patients and 39 BTKi-experienced patients. Among evaluable BTKi-naive patients, defined as those who completed at least 1 cycle (approximately 1 month) of treatment, the ORR was 100% (n = 5/5). Among all 7 BTKi-naive patients, the ORR was 86%, an increase from 71% in data reported as of May 1, 2025.

Among BTKi-experienced patients, the ORR was 33% among 30 evaluable patients and 26% among all 39 patients compared with 27% in the prior dataset. The sponsor noted that BTKi-experienced patients represent a population without approved therapies, as this group generally has poor outcomes and limited options once disease progresses on BTKi monotherapy, with many patients proceeding to hospice or best supportive care.

"We are very encouraged by the updated data from the PCNSL study and by the support of clinicians and regulators for this novel treatment for patients with PCNSL,” said James Dentzer, CEO of Curis, in a news release.¹ “We are especially excited by the results in the BTKi-experienced patients for whom there are no approved therapies, where emavusertib has shown it can reverse disease progression in patients currently progressing on a BTK inhibitor and enable them to achieve objective responses."

Emavusertib Mechanism of Action

Emavusertib is an oral, small molecule inhibitor of IRAK4 and FLT3 that is being developed to pair with BTKi therapy across B-cell malignancies, including PCNSL and chronic lymphocytic leukemia (CLL). The rationale for combining emavusertib with a BTKi is to achieve dual blockade of NF-kB signaling, which drives disease in both PCNSL and CLL. BTKi therapy inhibits the B-cell receptor (BCR) pathway, while emavusertib inhibits the Toll-like receptor (TLR) pathway. Together, the combination is intended to block both upstream drivers of NF-kB activation.

About the TakeAim Lymphoma Study

TakeAim Lymphoma is a multicenter, open-label dose-escalation and -expansion trial evaluating evaluating emavusertib as a single agent and in combination with ibrutinib in patients with relapsed/refractory PCNSL.² Approximately 181 patients are planned for enrollment across the study's 3 planned parts, with combination dosing of ibrutinib evaluated at 560 mg once daily.

A similar phase 2 study, TakeAim CLL (NCT07271667), is separately enrolling patients to evaluate emavusertib combined with zanubrutinib (Brukinsa) in patients with CLL who have residual disease on zanubrutinib monotherapy.

Regulatory History

Both TakeAim studies have previously faced FDA scrutiny over rhabdomyolysis, a known dose-limiting toxicity of emavusertib. In April 2022, the FDA's Division of Hematologic Malignancies 2 placed a partial clinical hold on TakeAim Lymphoma, requesting additional safety and efficacy data before allowing continued enrollment. The hold was lifted approximately 4.5 months later in August 2022, after the sponsor developed a strategy for identifying and managing rhabdomyolysis and agreed to enroll at least 9 additional patients at the 200-mg dose level of emavusertib in combination with ibrutinib.³

REFERENCES

1. Curis Announces Positive Emavusertib Update. News release. Curis. July 22, 2026. Accessed July 28, 2026. https://tinyurl.com/mr2tmcfe

2. CA-4948-101: Open-Label, Dose Escalation and Expansion Trial of Emavusertib (CA-4948) in Relapsed or Refractory Primary Central Nervous System Lymphoma (R/​R PCNSL). ClinicalTrials.gov. Updated April 16, 2026. Accessed July 28, 2026. https://clinicaltrials.gov/study/NCT03328078

3. FDA Lifts Partial Clinical Hold on the TakeAim Lymphoma Study of Emavusertib. News release. Curis. August 18, 2022. Accessed July 28, 2026. https://tinyurl.com/495xex7h