Study of BGB-10188 as Monotherapy, and in Combination With Zanubrutinib, and Tislelizumab

Browse trials for

• Leukemia, Lymphocytic, Chronic, B-Cell 1,603
• Lymphoma, Follicular 931
• Lymphoma, B-Cell, Marginal Zone 414
• Lymphoma, Mantle-Cell 783
• Lymphoma, Large B-Cell, Diffuse 1,389

Leukemia, Lymphocytic, Chronic, B-Cell

1,603 studies on the registry are indexed under Leukemia, Lymphocytic, Chronic, B-Cell; 243 are open to participants now.

This study's enrollment of 97 is above the median of 40 across 1,325 interventional studies indexed under Leukemia, Lymphocytic, Chronic, B-Cell.

Lead sponsor

BeiGene is the lead sponsor of 122 studies on the registry; 3 are open to participants now.

Of its 52 completed or terminated interventional studies of FDA-regulated products, 31 (60%) have results posted.

Eligibility criteria

Study arms

• Experimental
  Part A: Dose Escalation- BGB-10188- 60 mg

  Participants with relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone lymphoma (MZL), follicular lymphoma (FL), mantle cell lymphoma (MCL) or diffuse large B-cell lymphoma (DLBCL) received BGB-10188 60 milligrams (mg) orally, once daily (QD) from Cycle 1 day 1 (C1D1) until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 28 days.

  Drug: BGB-10188

• Experimental
  Part A: Dose Escalation- BGB-10188- 120 mg

  Participants with R/R CLL/SLL, MZL, FL, MCL or DLBCL received BGB-10188 120 mg orally, QD from C1D1 until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 28 days.

  Drug: BGB-10188

• Experimental
  Part A: Dose Escalation- BGB-10188- 240 mg

  Participants with R/R CLL/SLL, MZL, FL, MCL or DLBCL received BGB-10188 240 mg orally, QD from C1D1 until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 28 days.

  Drug: BGB-10188

• Experimental
  Part A: Dose Escalation- BGB-10188- 360 mg

  Participants with R/R CLL/SLL, MZL, FL, MCL or DLBCL received BGB-10188 360 mg orally, QD from C1D1 until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 28 days.

  Drug: BGB-10188

• Experimental
  Part A: Dose Escalation- BGB-10188- 540 mg

  Participants with R/R CLL/SLL, MZL, FL, MCL or DLBCL received BGB-10188 540 mg orally, QD from C1D1 until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 28 days.

  Drug: BGB-10188

• Experimental
  Part B: Dose Escalation- BGB-10188- 240 mg + Zanubrutinib-160 mg

  Participants with R/R FL, MCL, and DLBCL received BGB-10188 240 mg orally, QD from C1D1 in combination with zanubrutinib 160 mg orally, twice a day (BID) until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 28 days.

  Drug: BGB-10188 · Drug: Zanubrutinib

• Experimental
  Part D: Dose Escalation- BGB-10188- 20 mg + Tislelizumab 200 mg

  Participants with unresectable locally advanced or metastatic solid tumors received BGB-10188 20 mg orally, QD from C1D1, followed by tislelizumab 200 mg intravenously (IV) on C1D8 and Day 1 of all subsequent cycles until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. The duration of Cycle 1 was 28 days and the duration of each cycle from Cycle 2 onwards was 21 days.

  Drug: BGB-10188 · Drug: Tislelizumab

• Experimental
  Part D: Dose Escalation- BGB-10188- 40 mg + Tislelizumab 200 mg

  Participants with unresectable locally advanced or metastatic solid tumors received BGB-10188 40 mg orally, QD from C1D1, followed by tislelizumab 200 mg IV on C1D8 and Day 1 of all subsequent cycles until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. The duration of Cycle 1 was 28 days and the duration of each cycle from Cycle 2 onwards was 21 days.

  Drug: BGB-10188 · Drug: Tislelizumab

• Experimental
  Part D: Dose Escalation- BGB-10188- 80 mg + Tislelizumab 200 mg

  Participants with unresectable locally advanced or metastatic solid tumors received BGB-10188 80 mg orally, QD from C1D1, followed by tislelizumab 200 mg IV on C1D8 and Day 1 of all subsequent cycles until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. The duration of Cycle 1 was 28 days and the duration of each cycle from Cycle 2 onwards was 21 days.

  Drug: BGB-10188 · Drug: Tislelizumab

• Experimental
  Part D: Dose Escalation- BGB-10188- 160 mg + Tislelizumab 200 mg

  Participants with unresectable locally advanced or metastatic solid tumors received BGB-10188 160 mg orally, QD from C1D1, followed by tislelizumab 200 mg IV on C1D8 and Day 1 of all subsequent cycles until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. The duration of Cycle 1 was 28 days, and the duration of each cycle from Cycle 2 onwards was 21 days.

  Drug: BGB-10188 · Drug: Tislelizumab

• Experimental
  Part D: Dose Escalation- BGB-10188- 320 mg + Tislelizumab 200 mg

  Participants with unresectable locally advanced or metastatic solid tumors received BGB-10188 320 mg orally, QD from C1D1, followed by tislelizumab 200 mg IV on C1D8 and Day 1 of all subsequent cycles until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. The duration of Cycle 1 was 28 days and the duration of each cycle from Cycle 2 onwards was 21 days.

  Drug: BGB-10188 · Drug: Tislelizumab

• Experimental
  Part D: Dose Escalation- BGB-10188- 540 mg + Tislelizumab 200 mg

  Participants with unresectable locally advanced or metastatic solid tumors received BGB-10188 540 mg orally, QD from C1D1, followed by tislelizumab 200 mg IV on C1D8 and Day 1 of all subsequent cycles until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. The duration of Cycle 1 was 28 days, and the duration of each cycle from Cycle 2 onwards was 21 days.

  Drug: BGB-10188 · Drug: Tislelizumab

• Experimental
  Part E: Dose Expansion- BGB-10188- 160 mg + Tislelizumab 200 mg

  Participants with platinum-resistant ovarian cancer (PROC) were randomized to receive BGB-10188 160 mg orally, QD from C1D1, followed by tislelizumab 200 mg IV on Day 1 of each cycle until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 21 days.

  Drug: BGB-10188 · Drug: Tislelizumab

• Experimental
  Part E: Dose Expansion- BGB-10188- 320 mg + Tislelizumab 200 mg

  Participants with PROC were randomized to receive BGB-10188 320 mg orally, QD from C1D1, followed by tislelizumab 200 mg IV on Day 1 of each cycle until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 21 days.

  Drug: BGB-10188 · Drug: Tislelizumab

Interventions

• DrugBGB-10188

  Administered as specified in the treatment arm

• DrugZanubrutinib

  Administered as specified in the treatment arm

  Also known as: BGB-3111, Brukinsa

• DrugTislelizumab

  Administered as specified in the treatment arm

  Also known as: BGB-A317, Tevimbra, Tizveni

Primary outcomes

1. Part A: The Recommended Dose for Expansion (RDFE) of BGB-10188 Monotherapy in Hematologic Malignancies

   The RDFE of BGB-10188 monotherapy in participants with hematologic malignancies was planned to be determined from safety, tolerability, pharmacokinetic (PK), and any other relevant and available data based on recommendations from the Safety Monitoring Committee. Part A dose-escalation enrolled participants with R/R CLL/SLL, MZL, FL, MCL, and DLBCL up to 540 mg, however the maximum tolerated dose was not reached and the RDFE could not be determined based on the data that were collected.

   Time frame: Up to 28 days

2. Part B: The RDFE of BGB-10188 in Combination With Zanubrutinib in Hematologic Malignancies

   The RDFE of BGB-10188 in combination with zanubrutinib was planned to be determined from safety, tolerability, PK, and any other relevant and available data obtained, based on recommendation of the Safety Monitoring Committee. The RDFE could not be determined since not all planned dose cohorts in this part of the study were enrolled and not enough data were collected to establish the RDFE.

   Time frame: Up to 28 days

3. Part D: The RDFE of BGB-10188 in Combination With Tislelizumab in Advanced Solid Tumors

   The RDFE of BGB-10188 in combination with tislelizumab was determined based on the totality of safety, tolerability, PK, and any other relevant and available data that were obtained from the dose escalation phase for Part E.

   Time frame: Up to 28 days

4. Part E: Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1

   ORR was defined as the percentage of participants who had complete response (CR) or partial response (PR). Per RECIST v.1.1., CR was defined as disappearance of all target lesions, non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

   Time frame: Up to 10.0 months

5. Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation

   An AE was defined as any unfavorable and unintended sign, symptom, or disease associated with the use of study drugs, whether considered related to study drugs or not. An SAE was any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability, was a congenital anomaly or was considered a medically significant. TEAE was an AE that has an onset date or a worsening in severity from baseline on or after the first dose of study drug. Severity of AEs was assessed according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) v.5.0, which consists of: Grade 1 Mild; Grade 2 Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death due to AE.

   Time frame: Part A: 47.2 Months; Part B: 24 Months; Part D: 15.2 Months; Part E: 10 Months

Secondary outcomes

1. Parts A and B: ORR as Assessed by Investigator

   ORR was defined as the percentage of participants who had CR or PR as determined from investigator-derived tumor assessments per RECIST v. 1.1. Per RECIST v.1.1., CR was defined as disappearance of all target lesions, non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

   Time frame: Part A: up to 47.2 months and Part B: up to 24 months

2. Part A: Observed Maximum Plasma Concentration (Cmax) of BGB-10188 After a Single Dose

   Cmax of BGB-10188 after a single dose was determined.

   Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 168 hours post-dose on Day -7 (each cycle = 28 days)

3. Part A: Cmax of BGB-10188 at Steady State

   Cmax of BGB-10188 at steady state was determined.

   Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose on Cycle 1 Day 15 (each cycle = 28 days)

4. Part A: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) After Single Dose

   Area under the plasma concentration-time curve of BGB-10188 from time 0 to 24 hours (AUC0-24) was determined.

   Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8,12, and 24 hours post-dose on Day-7 (each cycle = 28 days)

5. Part B: Duration of Response (DOR)

   DOR was defined as the time from the first determination of an overall response per RECIST v1.1 until the first documentation of progression (PD) or death, whichever came first. Median DOR was estimated using the Kaplan-Meier method. Per RECIST v1.1., CR was defined as disappearance of all target lesions, non-target lesions, and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.

   Time frame: Up to 24 months

6. Part B: Time to Response (TTR)

   TRR was defined as the time from treatment initiation to the first documentation of response. Per RECIST v.1.1., CR was defined as disappearance of all target lesions, non-target lesions, and no new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

   Time frame: Up to 24 months

7. Part B: Cmax of BGB-10188 After a Single Dose

   Cmax of BGB-10188 after a single dose when given in combination with zanubrutinib was determined.

   Time frame: Pre-dose, 0.5,1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Cycle 1 Day 1 (each cycle = 28 days)

8. Part B: Cmax of BGB-10188 at Steady State

   Cmax of BGB-10188 at steady state when given in combination with zanubrutinib was determined.

   Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Cycle 1 Day 15 (each cycle = 28 days)

9. Part B: AUC 0-24 h of BGB-10188 After a Single Dose

   AUC 0-24 h of BGB-10188 after a single dose when given in combination with zanubrutinib was determined.

   Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Cycle 1 Day 1 (each cycle = 28 days)

10. Part D: Overall Response Rate (ORR)

    ORR was defined as the percentage of participants who had CR or PR as determined from investigator-derived tumor assessments per RECIST v. 1.1. Per RECIST v.1.1., CR was defined as disappearance of all target lesions, non-target lesions, and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    Time frame: Up to 15.2 months

11. Parts D and E: Duration of Response (DOR)

    DOR was defined as the time from the first determination of an overall response per RECIST v1.1 until the first documentation of PD or death, whichever came first. Median DOR was estimated using the Kaplan-Meier method. Per RECIST v1.1., CR was defined as disappearance of all target lesions, non-target lesions, and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment.

    Time frame: Part D: up to 15.2 months and Part E: up to 10.0 months

12. Parts D and E: Disease Control Rate (DCR)

    DCR was defined as the percentage of participants with best overall response (BOR), as per RECIST v.1.1, of a CR, PR, or stable disease (SD). Per RECIST v.1.1., CR was defined as disappearance of all target lesions, non-target lesions, and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

    Time frame: Part D: up to 15.2 months and Part E: up to 10.0 months

13. Parts D and E: Time to Response (TTR)

    TTR was defined as the time from treatment initiation to the first documentation of response. Per RECIST v.1.1., CR was defined as disappearance of all target lesions, non-target lesions, and no new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    Time frame: Part D: up to 15.2 months and Part E: up to 10.0 months

14. Part D: Cmax of BGB-10188 After a Single Dose

    Cmax of BGB-10188 after a single dose when given in combination with tislelizumab was determined.

    Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Cycle 1 Day 1 (each cycle = 28 days)

15. Part D: Cmax of BGB-10188 at Steady State

    Cmax of BGB-10188 at steady state when given in combination with tislelizumab was determined.

    Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Cycle 2 Day 1 (each cycle = 21 days)

16. Part D: AUC 0-24h of BGB-10188 After Single Dose

    AUC 0-24 h of BGB-10188 after a single dose when given in combination with tislelizumab was determined.

    Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Cycle 1 Day 1 (each cycle = 28 days)

17. Part D: AUC 0-24h of BGB-10188 at Steady State

    AUC 0-24 h of BGB-10188 at steady state when given in combination with tislelizumab was determined.

    Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Cycle 2 Day 1 (each cycle = 21 days)

18. Part E: Progression-Free Survival (PFS)

    PFS was defined as the time from the date of the first dose of study drugs to the date of the first documentation of PD assessed by the investigator using RECIST v1.1 or death, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Per RECIST v1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.

    Time frame: Up to 10.0 months

19. Part E: Clinical Benefit Rate (CBR)

    CBR was defined as the percentage of participants with best overall response, as defined by RECIST v1.1, of a CR, PR, or at least 24 weeks of SD. Per RECIST v.1.1., CR was defined as disappearance of all target lesions, non-target lesions, and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

    Time frame: Up to 10.0 months

20. Part E: Cancer Antigen (CA)-125 Response Rate Per Gynecological Cancer Intergroup

    CA-125 response rate was defined as the percentage of participants achieving a CA-125 response according to the Gynecological Cancer Center Intergroup criteria, in which a response had occurred if there was at least a 50% reduction in CA-125 levels from baseline.

    Time frame: Up to 10.0 months

21. Part E: Cmax of BGB-10188 After Single Dose

    Cmax of BGB-10188 after a single dose when given in combination with tislelizumab was determined.

    Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose on Cycle 1 Day 1 (each cycle = 21 days)

22. Part E: Cmax of BGB-10188 at Steady State

    Cmax of BGB-10188 at steady state when given in combination with tislelizumab was determined.

    Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose on Cycle 2 Day 1 (each cycle = 21 days)

23. Part E: AUC0-24h of BGB-10188 After Single Dose

    AUC0-24 h of BGB-10188 after a single dose when given in combination with tislelizumab was determined.

    Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose of Cycle 1 Day 1 (each cycle = 21 days)

Baseline characteristics

Study documents

• Study protocol · Apr 10, 2024
• Statistical analysis plan · Aug 16, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved. BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations. Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

Supporting information: Study protocol, Sap, Csr