Study of Bcl-2 Inhibitor BGB-11417 in Participants With Mature B-Cell Malignancies

Mature B-Cell Malignancies Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04277637
• Other study ID #: BGB-11417-101
• Status: Recruiting
• Phase: Phase 1
• Start date: March 24, 2020
• Est. completion date: August 30, 2027

Study information

• Verified date: June 2024
• Source: BeiGene
• Contact: BeiGene
• Phone: 1-877-828-5568
• Email: clinicaltrials[@]beigene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 537
• Est. completion date: August 30, 2027
• Est. primary completion date: August 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Confirmed diagnosis of one of the following:

NHL Cohorts:

1. 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

2. 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

3. 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)

4. 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:

5. 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:

6. 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)

• Measurable disease by computed tomography (CT)/magnetic resonance imaging (MRI),

defined as:

1. 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

2. 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
• Adequate pancreatic function indicated by:

1. Serum amylase = 1.5 x upper limit of normal (ULN)

2. 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.

Related Conditions & MeSH terms

• Mature B-Cell Malignancies
• Neoplasms

Intervention

Drug:
• BGB-11417
Film-coated tablets administered once daily at a dose as specified in the treatment arm
• 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)
• obinutuzumab
Given as an intravenous infusion administered per label.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Flinders Medical Centre	Bedford PK	South Australia
Australia	Pindara Private Hospital	Benowa	Queensland
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Monash Health	Clayton	Victoria
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	St Vincents Hospital Melbourne	Fitzroy	Victoria
Australia	Peter Maccallum Cancer Centre	Melbourne	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Linear Clinical Research	Nedlands	Western Australia
Australia	Orange Health Service (Central West Cancer Care Centre)	Orange	New South Wales
Australia	John Flynn Private Hospital	Tugun	Queensland
Germany	Universitatsklinikum Carl Gustav Carus An Der Technischen Universitat Dresden	Dresden
Germany	Universitaetsklinikum Ulm, Innere Medizin Iii	Ulm
Italy	Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda	Milano
Italy	Ospedale San Raffaele	Milano
Italy	Ospedale Santa Maria Della Misericordia	Perugia
Italy	Azienda Unita Sanitaria Locale Di Ravenna	Ravenna
Italy	Fondazione Policlinico Universitario Agostino Gemelli	Roma
Italy	Centroricerche Cliniche Di Verona Srl	Verona
New Zealand	Auckland City Hospital	Auckland
New Zealand	North Shore Hospital	Takapuna
New Zealand	Wellington Regional Hospital (Ccdhb)	Wellington
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital de La Santa Creu I Sant Pau	Barcelona
Spain	Ico H Duran I Reynals	Barcelona
Spain	Vall D Hebron Institute of Oncology Vhio	Barcelona
Spain	Start Madrid Fundacion Jimenez Diaz	Madrid
Spain	Clinica Universidad de Navarra Pamplona	Pamplona
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Marques de Valdecilla	Santander
United Kingdom	The Leeds Teaching Hospitals Nhs Trust	Leeds
United Kingdom	Oxford University Hospitals Nhs Foundation Trust	Oxford
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Northwestern University	Chicago	Illinois
United States	The James Cancer Hospital and Solove Research Institute At Ohio State University	Columbus	Ohio
United States	John Theurer Cancer Center Hackensack University Medical Center	Hackensack	New Jersey
United States	Md Anderson Cancer Center	Houston	Texas
United States	University of Kansas Medical Center Research Institute	Kansas City	Kansas
United States	UCLA Hematologyoncology	Los Angeles	California
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center Mskcc	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Upmc Hillman Cancer Center(Univ of Pittsburgh)	Pittsburgh	Pennsylvania
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

United States,  Australia,  Germany,  Italy,  New Zealand,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)		Up to 30 days after the last dose of study drug, an average of 18 months
Primary	Number of Participants Experiencing Serious Adverse Events (SAEs)		Up to 30 days after the last dose of study drug, an average of 18 months
Primary	Number of Participants Experiencing Adverse Events (AEs) leading to discontinuation of BGB-11417		Up to 30 days after the last dose of study drug, an average of 18 months
Primary	Part 1, Part 3: Maximum Tolerated Dose (MTD)		Day 1 to 21 days target dose of the study drug, an average of 18 months
Primary	Part 1, Part 3: Maximum RP2D of BGB-11417		Day 1 to last dose of study drug, an average of 18 months
Primary	Part 1, Part 3: Number of participants experiencing tumor lysis syndrome (TLS) relevant events		Up to 30 days after the last dose of study drug, an average of 18 months
Secondary	Maximum Observed Plasma Concentration (Cmax) of BGB-11417		Predose up to 12 hours postdose
Secondary	Area Under the Concentration-Time Curve from Time 0 to the Last Quantifiable Concentration (AUC0-last) of BGB-11417		Predose up to 12 hours postdose
Secondary	Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-8) of BGB-11417		Predose up to 12 hours postdose
Secondary	Time Taken for Half the Initial Dose Administered to Be Eliminated from The Body (T1/2) of BGB-11417		Predose up to 12 hours postdose
Secondary	Time to Maximum Plasma Concentration (Tmax) of BGB-11417		Predose up to 12 hours postdose
Secondary	Apparent Clearance (CL/F) of BGB-11417		Predose up to 12 hours postdose
Secondary	Apparent volume of distribution (Vz/F) of BGB-11417		Predose up to 12 hours postdose
Secondary	Steady State Area Under the Concentration-Time Curve of 0 - Last Day (AUCLast, ss) of BGB-11417		Predose up to 12 hours postdose
Secondary	Part 3, Part 4: Steady State Area Under the Concentration-Time Curve of 0 - Last Day (AUCLast, ss) of zanubrutinib		Predose up to 12 hours postdose
Secondary	Steady State Maximum Observed Plasma Concentration (Cmax, ss) of BGB-11417		Predose up to 12 hours postdose
Secondary	Part 3, Part 4: Steady State Maximum Observed Plasma Concentration (Cmax, ss) of zanubrutinib		Predose up to 12 hours postdose
Secondary	Steady State Trough Observed Plasma Concentration (Ctrough, SS) of BGB-11417		Predose up to 12 hours postdose
Secondary	Part 3, Part 4: Steady State Trough Observed Plasma Concentration (Ctrough, SS) of zanubrutinib		Predose up to 12 hours postdose
Secondary	Steady State Time to Maximum Plasma Concentration (Tmax, ss) of BGB-11417		Predose up to 12 hours postdose
Secondary	Part 3, Part 4: Steady State Time to Maximum Plasma Concentration (Tmax, ss) of zanubrutinib		Predose up to 12 hours postdose
Secondary	Part 2: AUC of BGB-11417 administered after a high fat/calorie meal (HF-Fed)		Predose up to 12 hours postdose
Secondary	Part 2: Cmax of BGB-11417 administered after a high fat/calorie meal (HF-Fed)		Predose up to 12 hours postdose
Secondary	Part 2, Part 4, Part 6: Overall Response Rate (ORR) as Assessed by the Investigator	ORR is defined as the proportion of participants who had confirmed complete response Complete Response (CR) or Partial Response (PR)	Up to 30 days after the last dose of study drug, an average of 18 months