New pill shows promise against rare brain cancer

NCT ID NCT04947319

Disease control Sponsor: Ono Pharmaceutical Co., Ltd. Source: ClinicalTrials.gov ↗

First seen Jun 26, 2026 · Last updated Jun 27, 2026 · Updated 1 time

Summary

This phase 2 trial tests tirabrutinib, a targeted cancer pill, in 119 people with primary central nervous system lymphoma (PCNSL), a rare brain cancer. Part A looks at patients whose cancer has returned or not responded to prior treatment. Part B tests tirabrutinib combined with chemotherapy in newly diagnosed patients. The goal is to see if the drug shrinks tumors and is safe.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: tirabrutinib (a targeted cancer drug taken as a pill)
What this could lead to: If successful, this could provide a new treatment option for primary CNS lymphoma, a rare brain cancer, potentially improving response rates.
What could go wrong: This is a mid-stage trial with a small number of participants. The drug may cause side effects or not work as well as hoped, and results may not apply to all patients.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 2

Tests whether the treatment actually works, and watches for side effects, in a larger group.

Participants

119 people

The number who actually took part.

Started

Dec 2021

Expected to finish

Mar 2027

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria (Part A) 1. Written informed consent by the patient prior to screening 2. Patients aged ≥ 18 years on the day of consenting to the study 3. Pathologic diagnosis of PCNSL 4. Relapse or refractory PCNSL with at least one prior high dose methotrexate (HD-MTX) based therapy for PCNSL 5. Measurable brain lesion with a minimum diameter \> 1.0 cm in gadolinium enhanced magnetic resonance imaging (MRI) performed within 14 days before starting tirabrutinib treatment 6. Eastern Cooperative Oncology Group performance score (ECOG PS) of 0, 1 or 2 7. Life expectancy of at least 3 months 8. Adequate bone marrow, renal, and hepatic function Inclusion Criteria (Part B) 1. Written informed consent by the patient prior to screening 2. Patients aged ≥ 18 years on the day of consenting to the study 3. Pathologic diagnosis of PCNSL within the past 3 months 4. No prior anti-tumor treatments for PCNSL 5. Patients who, in the opinion of the Investigator, are suitable to receive treatment with a high dose methotrexate containing regimen 6. Measurable brain lesion with a minimum diameter \> 1.0 cm in gadolinium enhanced MRI performed within 14 days before starting study treatment 7. ECOG PS of 0, 1 or 2 8. Life expectancy of at least 6 months 9. Adequate bone marrow, renal, and hepatic function Exclusion Criteria (Part A) 1. Intraocular PCNSL with no brain lesion 2. Patient who is intolerant of contrast enhanced MRI due to allergic reactions to contrast agents 3. Patient with non-B cell PCNSL 4. Patient with systemic presence of lymphoma 5. Prior chemotherapy within 21 days, nitrosourea within 42 days, an antibody drug with anticancer activity (e.g., rituximab) within 28 days, prior radiotherapy within 14 days, prior major invasive surgery within 28 days, or allogeneic stem cell transplant within 6 months before starting tirabrutinib treatment 6. Prior BTK inhibitor treatment 7. Prior investigational drugs (including treatment in clinical research, unapproved combination products, and new dosage forms) within 28 days or 5 half-lives, whichever is shorter, before starting tirabrutinib treatment 8. Concomitant systemic corticosteroid on an ongoing basis within 14 days before starting tirabrutinib treatment, with the exception of the following: * Equivalent of up to 10 mg/day of prednisone for a disease other than PCNSL * Equivalent of up to 50 mg/day of prednisone (equal to 8 mg/day of dexamethasone) for patients with lesions of the brain or spinal cord or both 9. Patient who has received a CYP3A4 inducer or P-gp inducer within 14 days before starting tirabrutinib treatment 10. Concomitant warfarin, any other warfarin derivative anticoagulant, vitamin K antagonists, novel oral anticoagulants, or antiplatelet therapy on an ongoing basis within 7 days before starting tirabrutinib treatment 11. Active malignancy, other than PCNSL requiring systemic therapy 12. Poorly controlled comorbidity, severe heart, severe lung disease, clinically significant liver diseases that could affect protocol compliance or safety or efficacy assessments 13. Patient with bleeding diathesis 14. Patients with a history of moderate or severe hepatic impairment 15. QTcF \> 480 milliseconds or requirement for ongoing treatment with concomitant medications that prolong the QT interval 16. Active infection, including a HIV, cytomegalovirus infection or SARS-CoV-2, or has had, within 28 days before starting tirabrutinib treatment, an infection (other than nail trichophytosis) that requires hospitalization or an intravenous antibiotic 17. Prior history of hypersensitivity or anaphylaxis to tirabrutinib 18. Prior history of Stevens Johnson Syndrome or Toxic Epidermal Necrolysis 19. Medical history of organ allografts 20. Tests positive for HIV-1 antibody and HIV-2 antibody, human T-lymphotropic virus 1 antibody, hepatitis B (HB) antigen, or hepatitis C virus (HCV) antibody. Tests positive for HBs antibody or hepatitis B virus core protein antibody and has a result of at least detectable in a hepatitis B virus deoxyribonucleic acid assay despite testing negative for HBs antigen. 21. Patient is unable to swallow tablets; has malabsorption, malabsorption syndrome, or a comorbidity that affects gastric function; has undergone complete resection of the stomach or small intestine; has ulcerative colitis or symptomatic inflammatory bowel disease; or has partial or complete intestinal obstruction. 22. Women who are pregnant or lactating 23. Patient is found incapable of giving consent due to dementia or another such condition 24. Patient is found to be otherwise ineligible for the study by the Investigator or sub-Investigator. Exclusion Criteria (Part B) 1. Intraocular PCNSL with no brain lesion 2. Patients for whom the selected backbone regimen medications (i.e, methotrexate/temozolomide/rituximab for MTR and rituximab/methotrexate/procarbazine/vincristine for R-MPV) are contraindicated 3. Patients with a history of intolerable toxicity, hypersensitivity, anaphylaxis to the selected backbone regimen medications 4. Patient who is intolerant of contrast enhanced MRI due to allergic reactions to contrast agents 5. Patient with non-B cell PCNSL 6. Patient with systemic presence of lymphoma 7. Prior chemotherapy within 21 days, nitrosourea within 42 days, an antibody drug with anticancer activity (e.g., rituximab) within 28 days, prior radiotherapy within 14 days, prior major invasive surgery within 28 days, or allogeneic stem cell transplant within 6 months before starting tirabrutinib treatment 8. Prior BTK inhibitor treatment 9. Prior investigational drugs (including treatment in clinical research, unapproved combination products, and new dosage forms) within 28 days or 5 half-lives, whichever is shorter, before starting tirabrutinib treatment 10. Concomitant systemic corticosteroid on an ongoing basis within 14 days before starting tirabrutinib treatment, with the exception of the following: * Equivalent of up to 10 mg/day of prednisone for a disease other than PCNSL * Equivalent of up to 50 mg/day of prednisone (equal to 8 mg/day of dexamethasone) for patients with lesions of the brain or spinal cord or both 11. Patient who has received a CYP3A4 inducer or P-gp inducer within 14 days before starting tirabrutinib treatment 12. Concomitant warfarin, any other warfarin derivative anticoagulant, vitamin K antagonists, novel oral anticoagulants, or antiplatelet therapy on an ongoing basis within 7 days before starting tirabrutinib treatment 13. Active malignancy, other than PCNSL requiring systemic therapy 14. Poorly controlled comorbidity, severe heart, severe lung disease, clinically significant liver diseases that could affect protocol compliance or safety or efficacy assessments 15. Patient with bleeding diathesis 16. Patients with a history of moderate or severe hepatic impairment 17. QTcF \> 480 milliseconds or requirement for ongoing treatment with concomitant medications that prolong the QT interval 18. Active infection, including a HIV, cytomegalovirus infection or SARS-CoV-2, or has had, within 28 days before starting tirabrutinib treatment, an infection (other than nail trichophytosis) that requires hospitalization or an intravenous antibiotic 19. Prior history of hypersensitivity or anaphylaxis to tirabrutinib 20. Prior history of Stevens Johnson Syndrome or Toxic Epidermal Necrolysis 21. Medical history of organ allografts 22. Tests positive for HIV-1 antibody and HIV-2 antibody, human T-lymphotropic virus 1 antibody, HBs antigen, or HCV antibody. Tests positive for HBs antibody or hepatitis B virus core protein antibody and has a result of at least detectable in a hepatitis B virus deoxyribonucleic acid assay despite testing negative for HBs antigen. 23. Patient is unable to swallow tablets; has malabsorption, malabsorption syndrome, or a comorbidity that affects gastric function; has undergone complete resection of the stomach or small intestine; has ulcerative colitis or symptomatic inflammatory bowel disease; or has partial or complete intestinal obstruction. 24. Women who are pregnant or lactating 25. Patient is found incapable of giving consent due to dementia or another such condition 26. Patient is found to be otherwise ineligible for the study by the Investigator or sub-Investigator.

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Conditions

The condition(s) this trial relates to.

primary central nervous system lymphoma

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Primary CNS lymphoma Refractory primary central nervous system lymphoma

Contacts and locations

Locations

Abramson Cancer Center University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States
Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States
City of Hope Comprehensive Breast Cancer Center

Duarte, California, 91010, United States
Cleveland Clinic

Cleveland, Ohio, 44106, United States
Columbia University Irving Medical Center

New York, New York, 10032, United States
Dana-Farber Cancer Institute - Brigham & Women's Hospital

Boston, Massachusetts, 02215, United States
Duke University School of Medicine

Durham, North Carolina, 27705, United States
Georgetown University, Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20037, United States
Hackensack University Medical Center - John Theurer Cancer

Hackensack, New Jersey, 07601, United States
Henry Ford Hospital

Detroit, Michigan, 48202, United States
Hillman Cancer Center, University of Pittsburgh

Pittsburgh, Pennsylvania, 15232, United States
Houston Methodist Research Institute (HMRI)

Houston, Texas, 77030, United States
Levine Cancer Center

Charlotte, North Carolina, 28204, United States
Lifespan Rhode Island Hospital

Providence, Rhode Island, 02903, United States
MD Anderson Cancer Center

Houston, Texas, 77030, United States
Massachusetts General Hospital

Boston, Massachusetts, 02114, United States
Mayo Clinic- Jacksonville

Jacksonville, Florida, 32224, United States
Mayo Clinic- Phoenix

Phoenix, Arizona, 85054, United States
Memorial Sloan Kettering

New York, New York, 10022, United States
Moffitt Cancer Center- Miami

Pembroke Pines, Florida, 33028, United States
Orlando Health

Orlando, Florida, 32806, United States
Penn State Hershey Cancer Center

Hershey, Pennsylvania, 17033, United States
Piedmont Healthcare

Atlanta, Georgia, 30318, United States
Providence Health Cancer Center

Portland, Oregon, 97239, United States
Roswell Park Comprehensive Cancer Center (RPCCC) (Roswell Park Cancer Institute (RPCI))

Buffalo, New York, 14263, United States
Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States
Stanford University

Palo Alto, California, 94304, United States
The University of Kansas Cancer Center (KUCC) (Kansas City Cancer Center (KCCC)) - North

Kansas City, Missouri, 64154, United States
The University of Utah - Huntsman Cancer Institute (HCI)

Salt Lake City, Utah, 84112, United States
The University of Vermont - Fletcher Allen Health Care

Burlington, Vermont, 05401, United States
University Of Michigan

Ann Arbor, Michigan, 41809, United States
University of Alabama at Birmingham School of Medicine

Birmingham, Alabama, 35233, United States
University of California, Irvine

Irvine, California, 92868, United States
University of Colorado Denver

Aurora, Colorado, 80045, United States
University of Kentucky

Lexington, Kentucky, 40536, United States
University of Miami-Sylvester Cancer Center

Miami, Florida, 33136, United States
University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States
Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States
Yale Cancer Center

New Haven, Connecticut, 06510, United States

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