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

• ClinicalTrials.gov Identifier: NCT05471843
• Recruitment Status: Recruiting
• First Posted: July 25, 2022
• Last Update Posted: April 25, 2024
• Sponsor: BeiGene
• Information provided by (Responsible Party): BeiGene

Tracking Information

• First Submitted Date: July 21, 2022
• First Posted Date: July 25, 2022
• Last Update Posted Date: April 25, 2024
• Actual Study Start Date: September 5, 2022
• Estimated Primary Completion Date: November 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 17, 2022)

• Part 1: Number Of Participants Experiencing Dose-limiting Toxicities (DLTs) [ Time Frame: 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. [ Time Frame: Up to 5 Years ]
• Part 1: Number of participants experiencing tumor lysis syndrome (TLS) relevant events [ Time Frame: Up to 5 Years ]
• Part 2: Overall Response Rate (ORR) as assessed by the Independent Review Committee (IRC) [ Time Frame: Up to 4 Years ]
  Defined as the proportion of participants who achieved a complete response (CR), or partial response (PR) per the Lugano Classification

Original Primary Outcome Measures (submitted: July 21, 2022)

• Part 1: Number Of Participants Experiencing Dose-limiting Toxicities (DLTs) [ Time Frame: Up to 1 Year ]
• Part 1: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 5 Years ]
  with adverse events leading to discontinuation, and AEs graded according NCI-CTCAE Version 5
• Part 1: Number of participants experiencing tumor lysis syndrome (TLS) relevant events [ Time Frame: Up to 5 Years ]
• Part 2: Overall Response Rate (ORR) as assessed by the Independent Review Committee (IRC) [ Time Frame: Up to 4 Years ]
  Defined as the proportion of participants who achieved a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) per the Lugano Classification

Current Secondary Outcome Measures (submitted: December 19, 2023)

• Part 1: Single Dose Area Under the Plasma Concentration Time Curve (AUC) [ Time Frame: Up to 2 Years ]
• Part 1: Single Dose Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Up to 2 Years ]
• Part 1: Single Dose Time to reach Cmax (Tmax) [ Time Frame: Up to 2 Years ]
• Part 1: Steady State Area Under the Plasma Concentration Time Curve (AUC) [ Time Frame: Up to 2 Years ]
• Part 1: Steady State Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Up to 2 Years ]
• Part 1: Steady State Trough Plasma Concentration (CTrough) [ Time Frame: Up to 2 Years ]
• Part 1: Steady State Time to reach Cmax (Tmax) [ Time Frame: Up to 2 Years ]
• Overall Response Rate (ORR) as assessed by investigator [ Time Frame: Up to 4 Years ]
  Defined as the proportion of participants who achieved a complete response (CR), or partial response (PR) per Lugano classification
• Duration of Response (DOR) as assessed by investigator and IRC [ Time Frame: Up to 4 Years ]
  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
• Progression Free Survival (PFS) as assessed by investigator and IRC [ Time Frame: Up to 4 Years ]
  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.
• Time to Response (TTR) as assessed by investigator and IRC [ Time Frame: Up to 4 Years ]
  TTR is defined as the time from start of treatment to first documentation of response of Partial Response (PR) or better
• Overall Survival (OS) [ Time Frame: Up to 4 Years ]
  Defined as time from the start of treatment to the date of death due to any cause
• Part 2: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and adverse events leading to discontinuation. [ Time Frame: Up to 4 Years ]
• Part 2: Number of participants with clinically significant changes from baseline in vital signs [ Time Frame: Up to 4 Years ]
  Vital signs include blood pressure and pulse rate
• Part 2: Number of participants with clinically significant changes from baseline in clinical laboratory values [ Time Frame: Up to 4 Years ]
  Laboratory values include hematology, and clinical chemistry
• Part 2: Number of Participants With Clinically Significant Physical Examination Findings [ Time Frame: Up to 4 Years ]
  A Physical examination includes head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal and musculoskeletal systems
• Part 2: Participant Reported Outcomes as measured by NFLymSI-18 [ Time Frame: Up to 4 Years ]
  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.
• Part 2: Participant Reported Outcomes as measured by EQ-5D-5L questionnaires [ Time Frame: Up to 4 Years ]
  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).

Original Secondary Outcome Measures (submitted: July 21, 2022)

• Part 1:Area Under the Plasma Concentration Time Curve (AUC) [ Time Frame: Up to 2 Years ]
• Part 1:Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Up to 2 Years ]
• Part 1: Time to reach Cmax (Tmax) [ Time Frame: Up to 2 Years ]
• Part 1: Steady State Area Under the Plasma Concentration Time Curve (AUC) [ Time Frame: Up to 2 Years ]
• Part 1: Steady State Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Up to 2 Years ]
• Part 1: Steady State Trough Plasma Concentration (CTrough) [ Time Frame: Up to 2 Years ]
• Part 1: Steady State Time to reach Cmax (Tmax) [ Time Frame: Up to 2 Years ]
• Overall Response Rate (ORR) as assessed by investigator [ Time Frame: Up to 4 Years ]
  Defined as the proportion of participants who achieved a complete response (CR), or partial response (PR) per Lugano classification
• Duration of Response (DOR) as assessed by investigator and IRC [ Time Frame: Up to 4 Years ]
  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
• Progression Free Survival (PFS) as assessed by investigator and IRC [ Time Frame: Up to 4 Years ]
  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.
• Time to Response (TTR) as assessed by investigator and IRC [ Time Frame: Up to 4 Years ]
  TTR is defined as the time from start of treatment to first documentation of response of Partial Response (PR) or better
• Overall Survival (OS) [ Time Frame: Up to 4 Years ]
  defined as time from the start of treatment to the date of death due to any cause
• Part 2: Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to 4 Years ]
• Part 2: Number of participants with clinically significant changes from baseline in vital signs [ Time Frame: Up to 4 Years ]
  Vital signs include blood pressure and pulse rate
• Part 2: Number of participants with clinically significant changes from baseline in clinical laboratory values [ Time Frame: Up to 4 Years ]
  Laboratory values include hematology, clinical chemistry, coagulation, and urinalysis
• Number of Participants With Clinically Significant Physical Examination Findings [ Time Frame: Up to 4 Years ]
  A full physical examination includes head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal and musculoskeletal systems
• Participant Reported Outcomes as measured by NFLymSI-18 [ Time Frame: Up to 4 Years ]
  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.
• Participants Reported Outcome as measured by EQ-5D-5L questionnaires [ Time Frame: Up to 4 Years ]
  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).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of BGB-11417 Monotherapy in Participants With Relapsed or Refractory Mantle Cell Lymphoma
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Mantle Cell Lymphoma
• Refractory Mantle Cell Lymphoma (MCL)
• Relapsed Mantle Cell Lymphoma

Intervention

Drug: BGB-11417

Administered orally

Other Name: sonrotoclax

Study Arms

Experimental: Single Arm

Participants will receive sonrotoclax

Intervention: Drug: BGB-11417

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 19, 2023): 122
• Original Estimated Enrollment (submitted: July 21, 2022): 98
• Estimated Study Completion Date: August 2027
• Estimated Primary Completion Date: November 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

1. Histologically confirmed diagnosis of MCL
2. 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).
3. Relapsed/refractory disease
4. Presence of measurable disease
5. Availability of archival tissue confirming diagnosis of MCL, or willing to undergo fresh tumor biopsy
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2.
7. Adequate organ function

Key Exclusion Criteria:

1. Known central nervous system involvement by lymphoma
2. 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.
3. Prior exposure to a BCL-2 inhibitor (eg, venetoclax/ABT-199).
4. 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.
5. Clinically significant cardiovascular disease.
6. Major surgery or significant injury ≤ 4 weeks prior to start of study treatment.
7. Active fungal, bacterial or viral infection requiring systemic treatment.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: BeiGene; 1.877.828.5568; clinicaltrials@beigene.com

• Listed Location Countries: Argentina, Belgium, Brazil, Canada, China, France, Germany, Israel, Italy, Poland, Puerto Rico, Spain, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05471843
• Other Study ID Numbers: BGB-11417-201; CTR20221815 ( Other Identifier: ChinaDrugTrials )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

• Current Responsible Party: BeiGene
• Original Responsible Party: Same as current
• Current Study Sponsor: BeiGene
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: BeiGene
• Verification Date: April 2024