Study of BGB-11417 Monotherapy in Participants With Relapsed or Refractory Mantle Cell Lymphoma

Study Overview
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Brief Summary
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The study consists of two parts. Part 1 determines the safety and tolerability of BGB-11417 (sonrotoclax) monotherapy, the maximum tolerated dose, and the recommended Phase 2 dose of BGB-11417 monotherapy for relapsed or refractory mantle cell lymphoma. Part 2 evaluates efficacy of BGB-11417 monotherapy at the recommended Phase 2 dose with recommended ramp-up schedule from Part 1.

Official Title
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A Single-Arm, Open-Label, Multicenter Phase 1/2 Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of BCL2 Inhibitor BGB-11417 in Patients With Relapsed or Refractory Mantle Cell Lymphoma

Conditions
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Mantle Cell Lymphoma, Refractory Mantle Cell Lymphoma (MCL), Relapsed Mantle Cell Lymphoma

Intervention / Treatment
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* Drug: BGB-11417


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically confirmed diagnosis of MCL Prior systemic treatments for MCL (at least one line of anti-cluster of differentiation 20 (anti-CD20) based immune or chemoimmunotherapy and at least one kind of covalent or non-covalent adequate Bruton Tyrosine Kinase (BTK) inhibitor). Relapsed/refractory disease Presence of measurable disease Availability of archival tissue confirming diagnosis of MCL, or willing to undergo fresh tumor biopsy Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2. Adequate organ function Key Exclusion Criteria: Known central nervous system involvement by lymphoma Prior malignancy other than MCL within the past 3 years, except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score 6 prostate cancer. Prior exposure to a BCL-2 inhibitor (eg, venetoclax/ABT-199). Prior autologous stem cell transplant within the last 3 months; or prior autologous chimeric antigen receptor T-cell therapy within the last 3 months; or prior allogeneic stem cell transplant within the last 6 months or currently has an active graft-vs-host disease requiring the use of immunosuppressants. Clinically significant cardiovascular disease. Major surgery or significant injury ≤ 4 weeks prior to start of study treatment. Active fungal, bacterial or viral infection requiring systemic treatment. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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: Single Arm<br>Participants will receive sonrotoclax | Drug: BGB-11417<br>* Administered orally<br>* Other names: sonrotoclax;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number Of Participants Experiencing Dose-limiting Toxicities (DLTs) |  | Up to 1 Year | 
| Part 1: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and adverse events leading to discontinuation. |  | Up to 5 Years | 
| Part 1: Number of participants experiencing tumor lysis syndrome (TLS) relevant events |  | Up to 5 Years | 
| Part 2: Overall Response Rate (ORR) as assessed by the Independent Review Committee (IRC) | Defined as the proportion of participants who achieved a complete response (CR), or partial response (PR) per the Lugano Classification | Up to 4 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Single Dose Area Under the Plasma Concentration Time Curve (AUC) |  | Up to 2 Years | 
| Part 1: Single Dose Maximum Observed Plasma Concentration (Cmax) |  | Up to 2 Years | 
| Part 1: Single Dose Time to reach Cmax (Tmax) |  | Up to 2 Years | 
| Part 1: Steady State Area Under the Plasma Concentration Time Curve (AUC) |  | Up to 2 Years | 
| Part 1: Steady State Maximum Observed Plasma Concentration (Cmax) |  | Up to 2 Years | 
| Part 1: Steady State Trough Plasma Concentration (CTrough) |  | Up to 2 Years | 
| Part 1: Steady State Time to reach Cmax (Tmax) |  | Up to 2 Years | 
| Overall Response Rate (ORR) as assessed by investigator | Defined as the proportion of participants who achieved a complete response (CR), or partial response (PR) per Lugano classification | Up to 4 Years | 
| Duration of Response (DOR) as assessed by investigator and IRC | DOR is defined as the time from the date of the first documented response (PR or better) after treatment initiation until the date of first documented disease progression or death due to any cause; whichever occurs first | Up to 4 Years | 
| Progression Free Survival (PFS) as assessed by investigator and IRC | PFS is defined as the time from the date of the first study dose until the date of first documented disease progression or death due to any cause, whichever occurs first. | Up to 4 Years | 
| Time to Response (TTR) as assessed by investigator and IRC | TTR is defined as the time from start of treatment to first documentation of response of Partial Response (PR) or better | Up to 4 Years | 
| Overall Survival (OS) | Defined as time from the start of treatment to the date of death due to any cause | Up to 4 Years | 
| Part 2: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and adverse events leading to discontinuation. |  | Up to 4 Years | 
| Part 2: Number of participants with clinically significant changes from baseline in vital signs | Vital signs include blood pressure and pulse rate | Up to 4 Years | 
| Part 2: Number of participants with clinically significant changes from baseline in clinical laboratory values | Laboratory values include hematology, and clinical chemistry | Up to 4 Years | 
| Part 2: Number of Participants With Clinically Significant Physical Examination Findings | A Physical examination includes head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal and musculoskeletal systems | Up to 4 Years | 
| Part 2: Participant Reported Outcomes as measured by NFLymSI-18 | The National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lymphoma Cancer Symptom Index-18 (FLymSI-18) questionnaire contains 18 items, each of which utilizes a Likert scale with 5 possible responses ranging from 0 'Not at all' to 4 'Very much' and is divided into a total score. | Up to 4 Years | 
| Part 2: Participant Reported Outcomes as measured by EQ-5D-5L questionnaires | The EQ-5D-5L descriptive system assesses health in five dimensions (MOBILITY, SELF-CARE, USUAL ACTIVITIES, PAIN / DISCOMFORT, ANXIETY / DEPRESSION), each of which has five levels of response (no problems, slight problems, moderate problems, severe problems, extreme problems/unable to). This part of the EQ-5D questionnaire provides a descriptive profile that can be used to generate a health state profile. Health state index scores generally range from less than 0 (where 0 is the value of a health state equivalent to dead; negative values representing values as worse than dead) to 1 (the value of full health), with higher scores indicating higher health utility. The second part of the questionnaire consists of a visual analogue scale (VAS) on which the participant rates his/her perceived health from 0 (the worst imaginable health) to 100 (the best imaginable health). | Up to 4 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mantle Cell Lymphoma, Lymphoma, MCL, Refractory MCL, Refractory Mantle Cell Lymphoma, Relapsed Mantle Cell Lymphoma