This is a study for participants with a type of blood cancer called mantle cell lymphoma (MCL). The main purpose is to compare 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.
Recruiting
Phase 3
| Drug | Synonyms | Arms |
|---|---|---|
| LOXO-305 | pirtobrutinib | Arm A (LOXO-305) |
| Ibrutinib | Imbruvica | Arm B (ibrutinib, acalabrutinib, or zanubrutinib) |
| Acalabrutinib | Calquence | Arm B (ibrutinib, acalabrutinib, or zanubrutinib) |
| Zanubrutinib | Brukinsa | Arm B (ibrutinib, acalabrutinib, or zanubrutinib) |
This is a Phase 3 global, randomized, open-label study comparing LOXO-305 (Arm A) to investigator's choice of ibrutinib, acalabrutinib or zanubrutinib (Arm B) in MCL patients who have received 1 or more lines of therapy and are BTK inhibitor naïve.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Arm A (LOXO-305) | Experimental | Orally |
|
| Arm B (ibrutinib, acalabrutinib, or zanubrutinib) | Active Comparator | Orally |
|
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
- Clinically significant active malabsorption syndrome or other condition likely to
affect gastrointestinal (GI) absorption
- Current treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers
and/or strong P-gp inhibitors.
- Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K
antagonist.
- Vaccination with live vaccine within 28 days prior to randomization
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | To compare progression-free survival (PFS) of LOXO-305 as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) in patients with previously treated mantle cell lymphoma (MCL) |
| Time Frame: | Up to approximately 24 months |
| Safety Issue: | |
| Description: | Assessed per Lugano criteria |
| Measure: | To compare Event Free Survival (EFS) as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms |
| Time Frame: | Up to approximately 24 months |
| Safety Issue: | |
| Description: | Defined as the time from randomization to progressive disease (PD) or start of new treatment for MCL or withdrawal from trial due to toxicity or death |
| Measure: | To compare Time to Treatment Failure (TTTF) as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms |
| Time Frame: | Up to approximately 24 months |
| Safety Issue: | |
| Description: | Time from randomization to time when discontinuation criteria met |
| Measure: | Time to worsening (TTW) of MCL-related symptoms |
| Time Frame: | Up to approximately 24 months |
| Safety Issue: | |
| Description: | Using symptom questions identified from the European Organization for Research and Treatment of Cancer (EORTC) item library. The range of raw scores for these items could be from 0 to 52 with highest score being worse symptoms. |
| Measure: | Comparative Tolerability as measured by proportion of time with high side effect burden |
| Time Frame: | Up to approximately 24 months |
| Safety Issue: | |
| Description: | Using 18 items covering 10 Patient Reported Outcome- Common Terminology Criteria for Adverse Events (PRO-CTCAE) concepts for frequency (0-5 with 5 as most frequent), and/or presence (0-1 with 1 being present), or Severity (0-5 with 5 as most severe) and/or presence (0-1 with 1 being present); these selective adverse events will be framed and then overall side effect burden will be ascertained with the Functional Assessment of Cancer Therapy (FACT) - Item GP5. The range of this item is 0 -4 with 4 as most bothersome. |
| Measure: | To compare Overall Response Rate (ORR) of LOXO-305 as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms |
| Time Frame: | Up to approximately 24 months |
| Safety Issue: | |
| Description: | Assessed per Lugano criteria |
| Measure: | To compare Duration of Response (DOR) of LOXO-305 as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms |
| Time Frame: | Up to approximately 24 months |
| Safety Issue: | |
| Description: | Assessed per Lugano criteria |
| Measure: | To compare Overall Survival of LOXO-305 as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms |
| Time Frame: | Up to approximately 24 months |
| Safety Issue: | |
| Description: | Assessed by survival |
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Loxo Oncology, Inc. |
August 24, 2021
