Study of Bcl-2 Inhibitor BGB-11417 in Participants With Mature B-Cell Malignancies
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| ClinicalTrials.gov Identifier: NCT04277637 |
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Recruitment Status :
Recruiting
First Posted : February 20, 2020
Last Update Posted : May 23, 2023
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Sponsor:
BeiGene
Information provided by (Responsible Party):
BeiGene
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Brief Summary:
The purpose of this study is to determine the safety, tolerability; and to define the maximum tolerated dose (MTD) and Recommended Phase 2 Dose (RP2D); and to evaluate the safety and tolerability of the ramp-up dosing schedule and at the RP2D of BGB-11417 monotherapy, and when given in combination with zanubrutinib and obinutuzumab.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Mature B-Cell Malignancies | Drug: BGB-11417 Drug: Zanubrutinib Drug: obinutuzumab | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 506 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1a/1b Open-Label Dose Escalation and Expansion Study of Bcl-2 Inhibitor BGB-11417 in Patients With Mature B-Cell Malignancies |
| Actual Study Start Date : | March 24, 2020 |
| Estimated Primary Completion Date : | August 30, 2025 |
| Estimated Study Completion Date : | August 30, 2025 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Zanubrutinib
| Arm | Intervention/treatment |
|---|---|
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Experimental: BGB-11417 Monotherapy Dose Finding: Part 1
Participants with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) including follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL) or transformed NHL, mantle cell lymphoma (MCL); Waldenströms macroglobulinemia (WM); and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) will receive oral BGB-11417 until the maximum tolerated dose (MTD) (or maximum ascending dose (MAD)) and recommended phase 2 dose can be determined
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Drug: BGB-11417
Film-coated tablets administered once daily at a dose as specified in the treatment arm |
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Experimental: BGB-11417 Monotherapy Expansion Cohorts: Part 2
Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; CLL/SLL with low tumor burden or low creatine clearance; CLL/SLL with without high tumor burden or low creatine clearance will receive oral BGB-11417 at the RP2D dose to further define the safety profile
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Drug: BGB-11417
Film-coated tablets administered once daily at a dose as specified in the treatment arm |
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Experimental: BGB-11417 + Zanubrutinib Combination Therapy Dose Finding: Part 3
Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; R/R MCL; R/R or treatment-naïve (TN) CLL/SLL will receive oral BGB-11417 until RP2D can be determined in combination with zanubrutinib
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Drug: BGB-11417
Film-coated tablets administered once daily at a dose as specified in the treatment arm Drug: Zanubrutinib 320 mg daily administered as two 80-mg capsules twice a day (160 mg twice a day) or as four 80-mg capsules once a day (320 mg once a day)
Other Name: BGB-3111 |
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Experimental: BGB-11417 + Zanubrutinib Combination Therapy Dose Expansion: Part 4
Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; R/R MCL; R/R or treatment-naïve (TN) CLL/SLL will receive oral BGB-11417 at an RP2D dose to further define the safety profile in combination with zanubrutinib
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Drug: BGB-11417
Film-coated tablets administered once daily at a dose as specified in the treatment arm Drug: Zanubrutinib 320 mg daily administered as two 80-mg capsules twice a day (160 mg twice a day) or as four 80-mg capsules once a day (320 mg once a day)
Other Name: BGB-3111 |
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Experimental: : BGB-11417 + Zanubrutinib Combination Therapy Dose Escalation: Part 5
Participants with treatment naïve CLL/SLL will receive oral BGB-11417 until RP2D can be determined in combination with obinutuzumab without and with zanubrutinib.
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Drug: BGB-11417
Film-coated tablets administered once daily at a dose as specified in the treatment arm Drug: Zanubrutinib 320 mg daily administered as two 80-mg capsules twice a day (160 mg twice a day) or as four 80-mg capsules once a day (320 mg once a day)
Other Name: BGB-3111 |
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Experimental: BGB-11417 + Zanubrutinib Combination Therapy Dose Expansion: Part 6
Participants with treatment naïve CLL/SLL will receive oral BGB-11417 at an RP2D dose to further define the safety profile in combination with obinutuzumab without and with zanubrutinib
|
Drug: BGB-11417
Film-coated tablets administered once daily at a dose as specified in the treatment arm Drug: Zanubrutinib 320 mg daily administered as two 80-mg capsules twice a day (160 mg twice a day) or as four 80-mg capsules once a day (320 mg once a day)
Other Name: BGB-3111 Drug: obinutuzumab Given as an intravenous infusion administered per label. |
Primary Outcome Measures :
- Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 30 days after the last dose of study drug, an average of 18 months ]
- Number of Participants Experiencing Serious Adverse Events (SAEs) [ Time Frame: Up to 30 days after the last dose of study drug, an average of 18 months ]
- Number of Participants Experiencing Adverse Events (AEs) leading to discontinuation of BGB-11417 [ Time Frame: Up to 30 days after the last dose of study drug, an average of 18 months ]
- Part 1, Part 3: Maximum Tolerated Dose (MTD) [ Time Frame: Day 1 to 21 days target dose of the study drug, an average of 18 months ]
- Part 1, Part 3: Maximum RP2D of BGB-11417 [ Time Frame: Day 1 to last dose of study drug, an average of 18 months ]
- Part 1, Part 3: Number of participants experiencing tumor lysis syndrome (TLS) relevant events [ Time Frame: Up to 30 days after the last dose of study drug, an average of 18 months ]
Secondary Outcome Measures :
- Maximum Observed Plasma Concentration (Cmax) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
- Area Under the Concentration-Time Curve from Time 0 to the Last Quantifiable Concentration (AUC0-last) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
- Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-∞) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
- Time Taken for Half the Initial Dose Administered to Be Eliminated from The Body (T1/2) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
- Time to Maximum Plasma Concentration (Tmax) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
- Apparent Clearance (CL/F) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
- Apparent volume of distribution (Vz/F) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
- Steady State Area Under the Concentration-Time Curve of 0 - Last Day (AUCLast, ss) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
- Part 3, Part 4: Steady State Area Under the Concentration-Time Curve of 0 - Last Day (AUCLast, ss) of zanubrutinib [ Time Frame: Predose up to 12 hours postdose ]
- Steady State Maximum Observed Plasma Concentration (Cmax, ss) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
- Part 3, Part 4: Steady State Maximum Observed Plasma Concentration (Cmax, ss) of zanubrutinib [ Time Frame: Predose up to 12 hours postdose ]
- Steady State Trough Observed Plasma Concentration (Ctrough, SS) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
- Part 3, Part 4: Steady State Trough Observed Plasma Concentration (Ctrough, SS) of zanubrutinib [ Time Frame: Predose up to 12 hours postdose ]
- Steady State Time to Maximum Plasma Concentration (Tmax, ss) of BGB-11417 [ Time Frame: Predose up to 12 hours postdose ]
- Part 3, Part 4: Steady State Time to Maximum Plasma Concentration (Tmax, ss) of zanubrutinib [ Time Frame: Predose up to 12 hours postdose ]
- Part 2: AUC of BGB-11417 administered after a high fat/calorie meal (HF-Fed) [ Time Frame: Predose up to 12 hours postdose ]
- Part 2: Cmax of BGB-11417 administered after a high fat/calorie meal (HF-Fed) [ Time Frame: Predose up to 12 hours postdose ]
- Part 2, Part 4, Part 6: Overall Response Rate (ORR) as Assessed by the Investigator [ Time Frame: Up to 30 days after the last dose of study drug, an average of 18 months ]ORR is defined as the proportion of participants who had confirmed complete response Complete Response (CR) or Partial Response (PR)
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Key Inclusion Criteria:
- Confirmed diagnosis of one of the following:
NHL Cohorts:
- MZL i. R/R extranodal, splenic, or nodal MZL defined as disease that relapsed after, or was refractory to, at least one prior therapy ii. Active disease requiring treatment
- FL i. R/R FL (Grade 1, 2 or 3a based on the WHO 2008 classification of tumors of hematopoietic and lymphoid tissue) and defined as disease that relapsed after, or was refractory to, at least 1 prior systemic therapy
- DLBCL i. R/R DLBCL (including all subtypes of DLBCL) defined as disease that relapsed after, or was refractory to, at least two prior systemic therapies and has either progressed following or is not a candidate for autologous stem cell transplant (due to comorbidities or non-responsiveness to salvage chemotherapy)
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Transformed indolent B-cell NHL i. Any lymphoma otherwise eligible for Part 1 that has transformed into a more aggressive lymphoma. Patients with transformation from CLL or SLL (Richter's transformation) are not eligible for Part 1
CLL/SLL Cohorts:
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CLL/SLL diagnosis that meets the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria i. Disease characterized as Treatment Naive (TN) or R/R disease defined as disease that relapsed after, or was refractory to, at least 1 prior therapy ii. Requiring treatment as defined by history
MCL cohorts:
- WHO-defined MCL I. R/R MCL defined as disease that relapsed after, or was refractory to, at least 1 prior systemic therapy; ii. Requiring treatment in the opinion of the investigatorr
WM cohorts:
g. WHO-defined WM (clinical and definitive histologic diagnosis) i. R/R disease defined as disease that relapsed after, or was refractory to, at least 1 prior therapy; ii. Meeting at least 1 criterion for treatment according to consensus panel criteria from the Seventh International Workshop on Waldenström's Macroglobulinemia (Dimopoulos et al 2014)
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Measurable disease by computed tomography (CT)/magnetic resonance imaging (MRI), defined as:
- CLL: at least 1 lymph node > 1.5 cm in longest diameter and measurable in 2 perpendicular dimensions or clonal lymphocytes measured by flow cytometry
- DLBCL, FL, MZL, SLL: at least 1 lymph node > 1.5 cm in longest diameter OR 1 extranodal lesion > 1.0 cm in the longest diameter, measurable in at least 2 perpendicular dimensions. For MZL, isolated splenomegaly is considered measurable for this study
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- Adequate organ function
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Adequate pancreatic function indicated by:
- Serum amylase ≤ 1.5 x upper limit of normal (ULN)
- Serum lipase ≤ 1.5 x ULN
Key Exclusion Criteria:
- Known central nervous system involvement by lymphoma/leukemia
- Known plasma cell neoplasm, prolymphocytic leukemia, history of or currently suspected Richter's syndrome
- Prior therapy ≥ 2 months with or progression on a B-cell lymphoma-2 (Bcl-2) inhibitor
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04277637
Contacts
| Contact: BeiGene | 1-877-828-5568 | clinicaltrials@beigene.com |
Locations
Show 54 study locations
Sponsors and Collaborators
BeiGene
Investigators
| Study Director: | David Simpson | BeiGene |
| Responsible Party: | BeiGene |
| ClinicalTrials.gov Identifier: | NCT04277637 |
| Other Study ID Numbers: |
BGB-11417-101 |
| First Posted: | February 20, 2020 Key Record Dates |
| Last Update Posted: | May 23, 2023 |
| Last Verified: | May 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by BeiGene:
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NHL BCL2 Inhibitor CLL MCL |
MZL SLL WM |
Additional relevant MeSH terms:
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Neoplasms Obinutuzumab Zanubrutinib Antineoplastic Agents, Immunological |
Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |