A Study of LOXO-305 in Chinese Participants With Blood Cancer (Including Lymphoma and Chronic Leukemia)

Study Overview
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Brief Summary
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A study of the safety, side effects, and effectiveness of LOXO-305 in Chinese adults with lymphoma or chronic leukemia who have already had standard of care treatment. Participation could last up to four years.

Official Title
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A Phase 2 Study of Oral LOXO-305 in Patients With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Non-Hodgkin Lymphoma (NHL)

Conditions
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Leukemia, Lymphoid, Lymphoma, Non-Hodgkin, Lymphoma, Mantle-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, B-Cell, Lymphoma, B-Cell, Marginal Zone, Leukemia, Lymphocytic, Chronic, B-Cell

Intervention / Treatment
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* Drug: LOXO-305


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Participants with histologically confirmed B-cell malignancy including: Mantle cell lymphoma (MCL) treated with a prior Bruton's tyrosine kinase (BTK) inhibitor containing regimen; CLL/SLL treated with a prior BTK inhibitor containing regimen; Other types of B-cell NHL All participants must have disease requiring treatment, for CLL/SLL participants, at least 1 indication for treatment consistent with IWCLL 2018 criteria is required Eastern Cooperative Oncology Group 0-2 Adequate hematologic status, coagulation, hepatic and renal function Exclusion Criteria Lack of adequate wash-out period for investigational agent or anticancer therapy, major surgery, and radiotherapy prior to the first dose of study treatment Participants requiring therapeutic anticoagulation with warfarin Known central nervous system (CNS) involvement by systemic lymphoma. Primary CNS lymphoma is excluded Significant cardiovascular disease Prolongation of the QT interval Test positive for human immunodeficiency virus (HIV) Current treatment with certain strong cytochrome P450 3A4 (CYP450 3A4) inhibitors or inducers and/or strong p-glycoprotein (P-gp) inhibitors Pregnancy or lactation Active second malignancy Prior treatment with LOXO-305 Known hypersensitivity to any component or excipient of LOXO-305

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LOXO-305<br>LOXO-305 administered orally. | Drug: LOXO-305<br>* Administered orally.<br>* Other names: Pirtobrutinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | ORR as assessed by an Independent Review Committee (IRC) | Randomization through Measured Progressive Disease (Estimated as up to 4 Years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR: Percentage of Participants Who Achieve CR or PR | ORR as assessed by the Investigator | Randomization through Measured Progressive Disease (Estimated as up to 4 Years) | 
| Best Overall Response (BOR): Percentage of Participants with CR, PR, Stable Disease (SD), or Progressive Disease (PD) | BOR as assessed by the Investigator and IRC | Randomization to Date of Objective Disease Progression (Estimated as up to 4 Years) | 
| Duration of Response (DOR) | DOR as assessed by the Investigator and IRC | Date of Partial Response (PR) or Better (PR with lymphocytosis or better for CLL/SLL, minor response or better for Waldenström macroglobulinemia) to Date of Disease Progression or Death Due to Any Cause (Estimated as up to 4 Years) | 
| Progression Free Survival (PFS) | PFS | Randomization to Objective Progression or Death Due to Any Cause (Estimated as up to 4 Years | 
| Overall Survival (OS) | OS | Randomization to Death from Any Cause (Estimated as up to 4 Years) | 
| 7. Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve from Time Zero to last (AUC[0-t) of LOXO-305 | PK: AUC(0-t) of LOXO-305 | Cycle 1 Day 1 Predose through Cycle 4 Day 1 Postdose (Cycle = 28 Days) | 
| PK: Maximum Concentration (Cmax) of LOXO-305 | PK: Cmax of LOXO-305 | Cycle 1 Day 1 Predose through Cycle 4 Day 1 Postdose (Cycle = 28 Days) | 
| Change from Baseline in Disease-Related Symptoms and Health-Related Quality of Life (HRQoL) measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Five physical function items identified in the EORTC-QLQ-C30 questionnaire (also known as the EORTC IL 19 questionnaire), will be measured. Raw scores for these items range from 0-20, with the highest score indicating worst function | Baseline through End of Treatment (Estimated as up to 3 Years) |