Study of Tirabrutinib vs Rituximab/Temozolomide for Relapsed/Refractory Primary Central Nervous System Lymphoma (PCNSL)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Deciphera Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2026-05-25

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Deciphera Pharmaceuticals, LLC

External identifiers

EU CT number

2025-523389-26-00

ClinicalTrials.gov

NCT07104032

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacogenetic, Efficacy, Safety

To investigate the efficacy of tirabrutinib monotherapy versus rituximab-temozolomide (R-TMZ) combination therapy as measured by progression-free survival (PFS) based on blinded Independent Review Committee (BIRC) assessment according to International Primary Central Nervous System Lymphoma Collaborative Group (IPCG) Criteria.

Secondary objectives 5

1. To compare the response rate (ORR) between treatment arms by BIRC.
2. To compare the overall survival (OS) between treatment arms.
3. To compare clinical efficacy between treatment arms by assessing complete response rate (CRR), best overall response (BOR), time to response (TTR), time to complete response (TTCR), duration of response (DOR), and disease-free survival (DFS) by BIRC
4. To evaluate the effect of treatment on corticosteroid requirements.
5. To evaluate the safety profile between treatment arms.

Conditions and MedDRA coding

Relapsed/refractory primary central nervous system lymphoma

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Written informed consent by the participant or legal authorized representative prior to Screening.
2. Pathology report confirming the diagnosis of B-cell PCNSL.
3. 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.
4. 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)
5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2.
6. Adequate bone marrow, renal, and hepatic function per central lab values.
7. Participants must agree to comply with all defined contraceptive requirements

Exclusion criteria 9

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 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 participants with lesions of the brain or spinal cord or both.
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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS based on blinded Independent Review Committee (BIRC) assessment according to International Primary Central Nervous System Lymphoma Collaborative Group (IPCG) criteria, defined as time from randomization to progressive disease (PD) or death due to any cause, whichever occurs first.

Secondary endpoints 9

1. ORR based on BIRC per IPCG criteria, defined as the percentage of participants with a best overall response of complete response (CR), unconfirmed complete response (CRu), or partial response (PR).
2. OS, defined as the time from randomization until death due to any cause.
3. CRR, BOR, TTR, TTCR, DOR, and DFS by BIRC: CRR based on BIRC per IPCG criteria, defined as the percentage of participants with a best overall response of CR or CRu
4. BOR based on BIRC per IPCG criteria, defined as the best response from randomization to the date of PD or the date of initiation of subsequent anticancer therapy for PCNSL, whichever occurs first.
5. TTR based on BIRC per IPCG criteria, defined as time between randomization and the date of first response of CR, CRu, or PR.
6. TTCR based on BIRC per IPCG criteria, defined as the time between randomization and the date of first complete response (CR or CRu).
7. DOR based on BIRC per IPCG criteria, defined as the time between the date of first response (CR, CRu, or PR) and the date of the first PD or date of death due to any cause, whichever occurs first.
8. DFS based on BIRC per IPCG criteria, defined as the time between the date of first complete response (CR or CRu) and the date of the first PD, or date of death due to any cause, whichever occurs first.
9. Change from baseline in Corticosteroid dose

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Deciphera Pharmaceuticals Inc.

Sponsor organisation

Deciphera Pharmaceuticals Inc.

Address

200 Smith Street

City

Waltham

Postcode

02451-0099

Country

United States

Scientific contact point

Organisation

Deciphera Pharmaceuticals Inc.

Contact name

Clinical Trial Information

Public contact point

Organisation

Deciphera Pharmaceuticals Inc.

Contact name

Clinical Trial Information

Third parties 13

Locations

8 EU/EEA countries · 32 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 76 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications