Clinical trial · Interventional
Study of BTK Inhibitor LOXO-305 Versus Approved BTK Inhibitor Drugs in Patients With Mantle Cell Lymphoma (MCL)
A Phase 3 Open-Label, Randomized Study of LOXO-305 Versus Investigator Choice of BTK Inhibitor in Patients With Previously Treated BTK Inhibitor Naïve Mantle Cell Lymphoma (BRUIN MCL-321)
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 26, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260926-000001
Summary
Brief summary (as posted)
This is a study for participants with a type of blood cancer called mantle cell lymphoma (MCL). The main purpose is to compare pirtobrutinib (LOXO-305) to other drugs that work in a similar way that have already been approved by the United States Food and Drug Administration (US FDA). Participation could last up to two years, and possibly longer, if the disease does not progress.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Lymphoma, Mantle-Cell | Mantle Cell Lymphoma | ALIAS | 0.90 |
Interventions
Interventions (4)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Acalabrutinib | Drug | Acalabrutinib | ALIAS |
| Ibrutinib | Drug | Ibrutinib | ALIAS |
| Pirtobrutinib | Drug | Pirtobrutinib | ALIAS |
| Zanubrutinib | Drug | Zanubrutinib | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Arm A (Pirtobrutinib)
- description
- Orally
- interventionNames
- Drug: Pirtobrutinib
- type
- ACTIVE_COMPARATOR
- label
- Arm B (Ibrutinib, Acalabrutinib, or Zanubrutinib)
- description
- Investigator's choice (based on local availability) of ibrutinib, acalabrutinib or zanubrutinib orally. Options are limited to those that are available/approved in the specific country.
- interventionNames
- Drug: Ibrutinib
- Drug: Acalabrutinib
- Drug: Zanubrutinib
Primary outcomes (1)
- measure
- To compare progression-free survival (PFS) of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) in patients with previously treated mantle cell lymphoma (MCL)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Confirmed MCL diagnosis * Previously treated with at least one prior line of systemic therapy for MCL * Measurable disease per Lugano criteria * Eastern Cooperative Oncology Group (ECOG) 0-2 * Absolute neutrophil count ≥ 0.75 × 109/L without granulocyte-colony stimulating factor support within 7 days of screening * Hemoglobin ≥ 8 g/dL not requiring transfusion support or growth factors within 7 days of screening * Platelets ≥ 50 × 109/L not requiring transfusion support or growth factors within 7 days of screening. * AST and ALT ≤ 3.0 x upper limit of normal (ULN) * Total bilirubin ≤ 1.5 x ULN. * Creatinine clearance of ≥ 30 mL/min according to Cockcroft/Gault Formula Exclusion Criteria: * Prior treatment with an approved or investigational BTK inhibitor * History of bleeding diathesis * History of stroke or intracranial hemorrhage within 6 months of randomization * History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor modified T-cell (CAR-T) therapy within 60 days of randomization * Clinically significant cardiovascular disease * Prolonged QT interval corrected using Fridericia's formula (QTcF) \> 470 ms on 2/3 consecutive ECGs, and mean QTcF\>470 ms on all 3 ECGs * Known HIV infection or active HBV, HCV, or CMV infections. (Certain participants with controlled HBV infections may still be eligible) * Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption * Ongoing chronic treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers which cannot be stopped within 3-5 half lives of the CYP3A inhibitor therapy prior to start of study drug treatment. * Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist. * Vaccination with live vaccine within 28 days prior to randomization
References
Publications (2)
- DERIVEDLoubert A, Creel K, Bhandari NR, Hess LM, Ruppert AS, Abada P, Regnault A, Payakachat N. Psychometric analysis of new lymphoma-specific patient-reported symptom measures derived from the EORTC item library. J Patient Rep Outcomes. 2026 Jun 22;10(1):109. doi: 10.1186/s41687-026-01126-w. PMID 42329537
- DERIVEDEyre TA, Shah NN, Dreyling M, Jurczak W, Wang Y, Cheah CY, Song Y, Gandhi M, Chay C, Sharman J, Andorsky DJ, Messersmith HM, Ruppert AS, Muthig VA, Ito R, Wang ML. BRUIN MCL-321: phase III study of pirtobrutinib versus investigator choice of BTK inhibitor in BTK inhibitor naive mantle cell lymphoma. Future Oncol. 2022 Nov;18(36):3961-3969. doi: 10.2217/fon-2022-0976. Epub 2022 Nov 15. PMID 36377973