FDA Accepts Tirabrutinib Application for Relapsed PCNSL

Deciphera Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has accepted for filing a new drug application for tirabrutinib for patients with relapsed or refractory primary central nervous system lymphoma, a rare and aggressive form of non-Hodgkin lymphoma with limited treatment options and a high unmet need for therapies with a favorable safety profile.

The application was submitted under the accelerated approval pathway and is supported by results from the phase 2 PROSPECT study. The FDA set a prescription drug user fee act action date of Dec. 18, 2026, meaning the agency is expected to decide by that date whether to approve the treatment.

Relapsed or refractory primary central nervous system lymphoma, often shortened to R/R PCNSL, occurs when the disease does not respond to initial treatment or returns after treatment. PCNSL is confined to the brain, spinal cord, eye or leptomeninges without systemic involvement. It is considered rare, with an annual incidence rate of approximately five cases per one million people in the United States. Rates can be higher among immunocompromised people aged 65 years and older.

Patients with PCNSL may experience symptoms that vary depending on where the lymphoma is located in the nervous system. These can include cranial neuropathy, neuropsychiatric symptoms, symptoms associated with increased intracranial pressure, seizures, ocular symptoms, headache, dysmotility and radiculopathy. Despite improvements in outcomes for newly diagnosed patients after induction treatment, approximately 20% to 30% of patients are refractory to initial therapy and up to 60% eventually experience relapse.

Main data that support the findings

The new drug application is based on positive results from the phase 2 PROSPECT study, which were presented at the 2025 American Society for Clinical Oncology Annual Meeting.

In the study, tirabrutinib demonstrated an overall response rate of 67%. This means that 67% of patients experienced tumor shrinkage or disappearance of detectable disease. The complete response rate was 44%, indicating that 44% of patients had no detectable evidence of disease following treatment.

The company reported that tirabrutinib showed a manageable safety profile in the study. These findings formed the basis for the regulatory submission under the accelerated approval pathway.

If approved, tirabrutinib would become the first Bruton tyrosine kinase inhibitor therapy commercially available in the United States for the treatment of patients with R/R PCNSL. It would also be the third commercial therapy for the Ono group available in the U.S.

Trial details

Tirabrutinib is a highly potent and selective Bruton tyrosine kinase inhibitor discovered and developed by Ono Pharmaceutical Co., Ltd. Bruton tyrosine kinase is part of the B-cell receptor signaling pathway. Signaling through the B-cell receptor regulates cellular proliferation and activation and promotes survival, differentiation and clonal expansion of B cells. This pathway plays an important role in several B-cell malignancies.

The phase 2 PROSPECT study evaluated tirabrutinib in patients with relapsed or refractory PCNSL. Based on the positive results from this study, the FDA accepted the application for filing.

A global phase 3 randomized trial is currently recruiting patients with R/R PCNSL. This trial is intended to serve as a confirmatory study for the indication.

Tirabrutinib has already received regulatory approvals in other countries. In Japan, it was approved in March 2020 for the treatment of R/R PCNSL and launched in May 2020 under the tradename Velexbru. It was subsequently approved in Japan in August 2020 for the treatment of Waldenstrom macroglobulinemia and lymphoplasmacytic lymphoma. Tirabrutinib was approved for R/R PCNSL in South Korea in November 2021 and in Taiwan in February 2022.

Safety

In the phase 2 PROSPECT study, tirabrutinib demonstrated a manageable safety profile, according to the company’s announcement. Specific side effects were not detailed in the press release.

The application was submitted under the accelerated approval pathway, which allows earlier approval of drugs that treat serious conditions and address unmet medical needs, based on clinical trial results that suggest a meaningful benefit. Continued approval may depend on confirmation of clinical benefit in the ongoing phase 3 randomized trial.

Reference

1. “Deciphera Pharmaceuticals Announces U.S. Food and Drug Administration Acceptance for Filing of New Drug Application for Tirabrutinib in Patients with Relapsed or Refractory PCNSL.” News Release. Deciphera Pharmaceuticals. Feb 17, 2026.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI and reviewed by a human editor.

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