Clinical trial NCT04277637: Study of Bcl-2 Inhibitor Sonrotoclax (BGB-11417) in Participants With Mature B-Cell Malignancies
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Mature B-Cell Malignancies
Keywords: NHL
BCL2 Inhibitor
CLL
MCL
MZL
SLL
WM
Bcl-2i
BTKi
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2020-02-20
Enrollment: 437
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 investigator

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, MCL, or 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
  3. WM: serum immunoglobulin (Ig) M level \> 0.5 g/dL
* 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 current 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.

Primary outcomes:
measure: Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to 30 days after the last dose of study drug, an average of 18 months
measure: Number of Participants Experiencing Serious Adverse Events (SAEs)
timeFrame: Up to 30 days after the last dose of study drug, an average of 18 months
measure: Number of Participants Experiencing Adverse Events (AEs) leading to discontinuation of Sonrotoclax
timeFrame: Up to 30 days after the last dose of study drug, an average of 18 months
measure: Part 1, Part 3: Maximum Tolerated Dose (MTD) of Sonrotoclax
timeFrame: Up to approximately 2 months
measure: Part 1, Part 3, Part 5: RP2D of Sonrotoclax
timeFrame: Day 1 to last dose of study drug, an average of 18 months
measure: Part 1, Part 3, Part 5: Number of participants experiencing tumor lysis syndrome (TLS) relevant events
timeFrame: Up to 30 days after the last dose of study drug, an average of 18 months
measure: Part 1, Part 3, Part 5: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs
timeFrame: Up to approximately 2 months
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) After a Single Dose of Sonrotoclax
timeFrame: Predose up to 12 hours postdose
measure: Area Under the Concentration-Time Curve from Time 0 to the Last Quantifiable Concentration (AUC0-last) After a Single Dose of Sonrotoclax
timeFrame: Predose up to 12 hours postdose
measure: Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-∞) After a Single Dose of Sonrotoclax
timeFrame: Predose up to 12 hours postdose
measure: Time Taken for Half the Initial Dose Administered to Be Eliminated from The Body (T1/2) of Sonrotoclax
timeFrame: Predose up to 12 hours postdose
measure: Time to Maximum Plasma Concentration (Tmax) After a Single Dose of Sonrotoclax
timeFrame: Predose up to 12 hours postdose
measure: Apparent Clearance (CL/F) After a Single Dose of Sonrotoclax
timeFrame: Predose up to 12 hours postdose
measure: Apparent volume of distribution (Vz/F) After a Single Dose of Sonrotoclax
timeFrame: Predose up to 12 hours postdose
measure: Steady State Area Under the Concentration-Time Curve of 0 - Last Day (AUCLast, ss) of Sonrotoclax
timeFrame: Predose up to 12 hours postdose
measure: Part 3, Part 4: Steady State Area Under the Concentration-Time Curve of 0 - Last Day (AUCLast, ss) of zanubrutinib
timeFrame: Predose up to 12 hours postdose
measure: Steady State Maximum Observed Plasma Concentration (Cmax, ss) of Sonrotoclax
timeFrame: Predose up to 12 hours postdose
measure: Part 3, Part 4: Steady State Maximum Observed Plasma Concentration (Cmax, ss) of zanubrutinib
timeFrame: Predose up to 12 hours postdose
measure: Steady State Trough Observed Plasma Concentration (Ctrough, ss) of Sonrotoclax
timeFrame: Predose up to 12 hours postdose
measure: Part 3, Part 4: Steady State Trough Observed Plasma Concentration (Ctrough, ss) of zanubrutinib
timeFrame: Predose up to 12 hours postdose
measure: Steady State Time to Maximum Plasma Concentration (Tmax, ss) of Sonrotoclax
timeFrame: Predose up to 12 hours postdose
measure: Part 3, Part 4: Steady State Time to Maximum Plasma Concentration (Tmax, ss) of zanubrutinib
timeFrame: Predose up to 12 hours postdose
measure: Part 2: AUC of Sonrotoclax administered after a high fat/calorie meal (HF-Fed)
timeFrame: Predose up to 12 hours postdose
measure: Part 2: Cmax of Sonrotoclax administered after a high fat/calorie meal (HF-Fed)
timeFrame: Predose up to 12 hours postdose
measure: Part 2, Part 4, Part 6: Overall Response Rate (ORR) as Assessed by the Investigator
timeFrame: Up to 18 months
measure: Part 2: Major Response Rate (MRR) for WM as Assessed by the Investigator
timeFrame: Up to 18 months
measure: Part 6: Minimum residual disease (MRD) negativity as measured by next generation sequencing
timeFrame: Up to 18 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Hematologyoncology
state: California
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center Research Institute
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Hackensack
country: United States
facility: John Theurer Cancer Center Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Mskcc
state: New York
city: Columbus
country: United States
facility: The James Cancer Hospital and Solove Research Institute At Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: Upmc Hillman Cancer Center(Univ of Pittsburgh)
state: Pennsylvania
city: Houston
country: United States
facility: Md Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Orange
country: Australia
facility: Orange Health Service (Central West Cancer Care Centre)
state: New South Wales
city: Benowa
country: Australia
facility: Pindara Private Hospital
state: Queensland
city: Tugun
country: Australia
facility: John Flynn Private Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Bedford PK
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincents Hospital Melbourne
state: Victoria
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus An Der Technischen Universitat Dresden
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
city: Perugia
country: Italy
facility: Ospedale Santa Maria Della Misericordia
city: Ravenna
country: Italy
facility: Azienda Unita Sanitaria Locale Di Ravenna
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
city: Verona
country: Italy
facility: Centroricerche Cliniche Di Verona Srl
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Takapuna
country: New Zealand
facility: North Shore Hospital
city: Wellington
country: New Zealand
facility: Wellington Regional Hospital (Ccdhb)
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Vall D Hebron Institute of Oncology Vhio
city: Barcelona
country: Spain
facility: Ico H Duran I Reynals
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Start Madrid Fundacion Jimenez Diaz
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra Pamplona
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Leeds
country: United Kingdom
facility: The Leeds Teaching Hospitals Nhs Trust
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: