Tirabrutinib versus rituximab plus temozolomide for relapsed or refractory primary central nervous system lymphoma

A Phase 3, Multi-regional, Open-label, Randomized Study of Tirabrutinib vs Rituximab and Temozolomide in Participants With Relapsed/Refractory Primary Central Nervous System Lymphoma

This trial tests whether the oral drug tirabrutinib works better alone than the combination of rituximab and temozolomide for people with relapsed or refractory primary CNS lymphoma.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 132 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ono Pharmaceutical Co., Ltd. (industry)
• Drugs / interventions: rituximab, methotrexate, prednisone, tirabrutinib
• Locations: 9 sites (Scottsdale, Arizona and 8 other locations)
• Trial ID: NCT07104032 on ClinicalTrials.gov

What this trial studies

This phase 3, interventional trial compares tirabrutinib monotherapy against the combination of rituximab and temozolomide in adults with relapsed or refractory B‑cell primary CNS lymphoma. Participants must have had at least one prior high‑dose methotrexate–based regimen and measurable brain lesions on contrast MRI. The study will follow patients for response and safety outcomes to determine whether tirabrutinib provides superior disease control or a different safety profile compared with R‑TMZ. Multiple U.S. cancer centers are participating under sponsorship from Ono Pharmaceutical with collaborator support from Deciphera.

Who should consider this trial

Good fit: Ideal candidates are adults with relapsed or refractory B‑cell primary CNS lymphoma who previously received at least one high‑dose methotrexate–based therapy, have a measurable brain lesion ≥1 cm on contrast MRI, ECOG performance status 0–2, and adequate organ function.

Not a fit: Patients with isolated intraocular or spinal PCNSL without brain lesions, those with ECOG >2, or those with inadequate organ function or contraindications to the study drugs are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, tirabrutinib could offer an effective targeted oral option that improves disease control or tolerability compared with rituximab plus temozolomide for relapsed/refractory PCNSL.

How similar studies have performed: Other BTK inhibitors such as ibrutinib have shown activity in CNS lymphoma, so this trial builds on prior positive signals though tirabrutinib itself has not been established in phase 3 for PCNSL.

Eligibility criteria

Inclusion Criteria

1. Pathology report confirming the diagnosis of B-cell PCNSL
2. Relapsed or refractory B-cell PCNSL with at least 1 prior high-dose methotrexate (HD-MTX) based therapy for PCNSL:

   * Relapsed disease: Participants who achieved a response (CR, CRu, PR) to the last treatment and subsequently experienced disease progression.
   * Refractory disease: Participants whose best response to the last treatment was stable disease or PD.
3. One or more bi-dimensionally measurable brain lesions with a minimum diameter greater than or equal to (≥)1 centimeter (cm) × ≥1 cm in gadolinium-enhanced magnetic resonance imaging (MRI)
4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2
5. Adequate bone marrow, renal, and hepatic function per central lab values
6. Participants must agree to comply with all defined contraceptive requirements

Exclusion Criteria

1. Participants with isolated intraocular PCNSL or spinal PCNSL with no brain lesions
2. Participants with non-B-cell PCNSL
3. Participants with systemic presence of lymphoma
4. Refractory to temozolomide with or without rituximab-containing regimens in the last PCNSL treatment
5. Concomitant systemic corticosteroid exposure within 14 days before starting study drug per Investigator assessment with the exception of the following:

   * Equivalent of up to 10 milligram per day (mg/day) of prednisone for a disease other than PCNSL
   * Equivalent of up to 50 mg/day of prednisone (equal to 8 mg/day dexamethasone) for participants with lesions of the brain and/or spinal cord
6. Active malignancy, other than PCNSL requiring systemic therapy
7. Poorly controlled comorbidity, or history of medical conditions contraindicated per Investigator assessment
8. Participants who are unable to swallow oral medication
9. Prior Bruton's tyrosine kinase inhibitor treatment

Where this trial is running

Scottsdale, Arizona and 8 other locations

• HonorHealth Cancer Center — Scottsdale, Arizona, United States (RECRUITING)
• Providence Medical Foundation — Fullerton, California, United States (RECRUITING)
• Yale Cancer Center — New Haven, Connecticut, United States (RECRUITING)
• Massachusetts General Hospital — Boston, Massachusetts, United States (RECRUITING)
• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States (RECRUITING)
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (RECRUITING)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (RECRUITING)
• Duke University Medical Center — Durham, North Carolina, United States (RECRUITING)
• UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania, United States (RECRUITING)

Study contacts

• Study coordinator: Clinical Team

Conditions: Relapsed/Refractory Primary Central Nervous System Lymphoma, Bruton's tyrosine kinase