Clinical trial NCT05006716: A Dose-Escalation and Expansion Study of BGB-16673 in Participants With B-Cell Malignancies
Official title: A Phase 1/2, Open-Label, Dose-Escalation and -Expansion Study of the Bruton Tyrosine Kinase Targeted Protein Degrader BGB-16673 in Patients With B-Cell Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: B-cell Malignancy
Marginal Zone Lymphoma
Follicular Lymphoma
Non-Hodgkin Lymphoma
Waldenström Macroglobulinemia
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Mantle Cell Lymphoma
Diffuse Large B Cell Lymphoma
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2021-08-16
Enrollment: 621
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Study consists of two main parts to explore BGB-16673 recommended dosing, a Phase 1 monotherapy dose finding comprised of monotherapy dose escalation and monotherapy safety expansion of selected doses, and a Phase 2 (expansion cohorts)


Eligibility criteria: Inclusion Criteria :

1. Confirmed diagnosis (per World Health Organization (WHO) guidelines, unless otherwise noted) of one of the following: Marginal Zone Lymphoma (MZL) , Follicular Lymphoma (FL), R/R Mantle Cell Lymphoma (MCL), R/R chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL), Waldenström macroglobulinemia (WM), Diffuse large B-cell lymphoma (DLBCL), or \>2 treatments per the Richter's transformation to DLBCL.
2. Participants who have previously received a covalently-binding Bruton´s tyrosine kinase (BTK) inhibitor (BTKi) in any line of therapy must have received treatment with the BTK inhibitor for ≥ 8 weeks (unless reason for discontinuation is intolerance).
3. For dose-finding and dose-expansion, participants who had previously received a covalently-binding BTK inhibitor as monotherapy or in combination with other anticancer agents are eligible for the study if they meet any of the following criteria: discontinued the previous BTK inhibitor due to disease progression, experienced disease progression after completing treatment with a BTK inhibitor or discontinued the BTK inhibitor due to toxicity or intolerance.
4. Measurable disease by radiographic assessment or serum IgM level (WM only)
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
6. Participants enrolling in the dose finding phase of the study may be previously treated with a BTKi or may be naïve to BTKi therapy depending on the diagnosis and country of enrollment; participants with MCL enrolling in the expansion cohorts (Phase 2) must have been treated with a BTKi in a prior line of therapy; CLL/SLL participants, in addition to being treated with a BTKi in a prior line of therapy, must also have received a Bcl-2 inhibitor in a prior line of therapy as well (Phase 2).

Exclusion Criteria:

1. Prior malignancy (other than the disease under study) within the past 2 years, except in situ malignancies that have been curatively resected, localized breast cancer treated with curative intent with no evidence of breast active disease for more than 3 years and receiving adjuvant hormonal therapy, localized Gleason score ≤ 6 prostate cancer undergoing observation or treatment with androgen depravation, or any other cancer treated with curative intent, not on adjuvant treatment, and in the opinion of the investigator is unlikely to recur.
2. Requires ongoing systemic treatment for any other malignancy
3. Requires ongoing systemic (defined as ≥ 10 mg/day of prednisone or equivalent) corticosteroid treatment.
4. Current or history of central nervous system involvement including the brain, spinal cord, leptomeninges, and cerebrospinal fluid (as documented by imaging, cytology, or biopsy) by B-cell malignancy, regardless of whether participants had received treatment for central nervous system disease
5. Known active plasma cell neoplasm, prolymphocytic leukemia, T-cell lymphoma, Burkitt lymphoma, acquired immunodeficiency syndrome (AIDS)-related B-cell lymphoma, Castleman disease, post-transplant lymphoproliferative disorders, hairy cell leukemia, germinal center B-cell (GCB), DLBCL, EBV+ DLBCL NOS, primary DLBCL of the central nervous system (CNS), primary cutaneous DLBCL - leg type, DLBCL associated with chronic inflammation, primary mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, ALK+ large B-cell lymphoma, primary effusion lymphoma, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, high-grade B-cell lymphoma - NOS, B-cell lymphoma unclassifiable with features intermediate between DLBCL and classical Hodgkin lymphoma, or history of or currently suspected transformation of an indolent lymphoma to an aggressive histology (except for participants with Richter Transformation to DLBCL are eligible for Part 1a, 1c, or Phase 2 and participants with history of follicular lymphoma transforming to non-GCB DLBCL who are eligible for Part 1a, 1c, or Phase 2).

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

Primary outcomes:
measure: Phase 1: Number of Participants with Adverse Events (AEs)
timeFrame: From the first dose of BGB-16673 until 30 days after the last dose of the study drug or before the initiation of a new anticancer therapy, whichever occurs first (Up to 47 weeks)
measure: Phase 1: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-16673
timeFrame: Approximately 28 days
measure: Phase 1: Recommended dose(s) for Expansion (RDFE) of BGB-16673
timeFrame: Approximately 28 days
measure: Phase 2: Overall response rate (ORR)
timeFrame: approximately 3 years
Secondary outcomes:
measure: Single dose and steady-state maximum observed plasma concentration (Cmax) of BGB-16673
timeFrame: Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose.
measure: Single dose and steady-state minimum observed plasma concentration (Cmin) of BGB-16673
timeFrame: Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose.
measure: Single dose and steady-state time to reach Cmax (tmax) of BGB-16673
timeFrame: Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose.
measure: Single dose and steady-state time to reach half of Cmax (T1/2) of BGB-16673
timeFrame: Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose.
measure: Single dose and steady-state area under the plasma concentration-time curve (AUC) of BGB-16673
timeFrame: Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose.
measure: Single dose and steady-state apparent total clearance of drug from plasma after oral administration (CL/F) of BGB-16673
timeFrame: Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose.
measure: Single dose and steady-state apparent volume of distribution (Vz/F) of BGB-16673
timeFrame: Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose.
measure: Single dose and steady-state accumulation ratios of BGB-16673
timeFrame: Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose.
measure: Bruton's tyrosine kinase (BTK) protein degradation in peripheral blood after BGB-16673 monotherapy
timeFrame: Week 1 Day 1 pre-dose; 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose and 8 hours post-dose; Week 9 Day 1 pre-dose.
measure: Phase 1: Overall response rate (ORR)
timeFrame: approximately 3 years
measure: Phase 1: Number of R/R WM Participants with major response rate (MRR)
timeFrame: approximately 3 years
measure: Phase 1: Number of Participants with AEs in part 1e (Japan-only cohort )
timeFrame: From the first dose of BGB-16673 in Part 1e until 30 days after the last dose of the study drug or before the initiation of a new anticancer therapy, whichever occurs first (approximately 3 years)
measure: Phase 2: Recommended Phase 2 Dose (RP2D)
timeFrame: approximately 3 years
measure: Phase 2: Number of Participants with AEs
timeFrame: From the first dose of BGB-16673 in Phase 2 until 30 days after the last dose of the study drug or before the initiation of a new anticancer therapy, whichever occurs first (approximately 3 years)
measure: Phase 2: Complete Response Rate (CRR)
timeFrame: approximately 3 years
measure: Phase 2: Response rate of minor response or better
timeFrame: approximately 3 years
measure: Phase 2: Duration of Response (DOR)
timeFrame: approximately 3 years
measure: Phase 2: Time to Response (TTR)
timeFrame: approximately 3 years
measure: Phase 2: Progression- Free Survival (PFS)
timeFrame: approximately 3 years
measure: Phase 2: Overall Survival (OS)
timeFrame: approximately 3 years
measure: Phase 2: Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionaire
timeFrame: Baseline and day 1 of Weeks 5, 13, 25, and 37
measure: Phase 2: National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lymphoma Cancer Symptom Index - 18 (NFLymSI-18)
timeFrame: Baseline and day 1 of Weeks 5, 13, 25, and 37
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama At Birmingham Hospital
state: Alabama
city: Goodyear
country: United States
facility: Western Regional Medical Center, Llc
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Phoenix
state: Arizona
city: Scottsdale
country: United States
facility: Honor Health Research Institute
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego (Ucsd) Moores Cancer Center
state: California
city: Palo Alto
country: United States
facility: Stanford Medicine
state: California
city: Santa Monica
country: United States
facility: UCLA Santa Monica Cancer Care
state: California
city: Fort Collins
country: United States
facility: Uchealth North
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital Cancer Institute
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Newnan
country: United States
facility: Southeastern Regional Medical Center
state: Georgia
city: Zion
country: United States
facility: Midwestern Regional Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Louisville
country: United States
facility: Norton Cancer Institute Pavilion
state: Kentucky
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center
state: Louisiana
city: Bethesda
country: United States
facility: American Oncology Partners of Maryland Pa
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College Newyork Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Mskcc
state: New York
city: Chattanooga
country: United States
facility: Tennesse Oncology Chattanooga
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, Pllc Nashville
state: Tennessee
city: Houston
country: United States
facility: Md Anderson Cancer Center
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
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: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Fitzroy
country: Australia
facility: St Vincents Hospital Melbourne
state: Victoria
city: Frankston
country: Australia
facility: Peninsula Private Hospital
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
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: West Perth
country: Australia
facility: Perth Blood Institute
state: Western Australia
city: Brasilia
country: Brazil
facility: Hospital Sirio Libanes Brasilia
city: Caxias do Sul
country: Brazil
facility: Instituto de Pesquisa Em Saude Da Universidade de Caxias Do Sul
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner
city: Porto Alegre
country: Brazil
facility: Centro Gaucho Integrado de Oncologia Hospital Mae de Deus
city: Porto Alegre
country: Brazil
facility: Hospital Ernesto Dornelles
city: Sao Paulo
country: Brazil
facility: Real E Benemerita Associacao Portuguesa de Sao Paulo
city: Sao Paulo
country: Brazil
facility: Hospital Alemao Oswaldo Cruz
city: Sao Paulo
country: Brazil
facility: Hospital Nove de Julho Dasa
city: Sao Paulo
country: Brazil
facility: Instituto Dor de Pesquisa E Ensino Sao Paulo
city: Sao Paulo
country: Brazil
facility: Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
city: Vitoria
country: Brazil
facility: Hospital Santa Rita de Cassia Afecc
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency the Vancouver Centre
state: British Columbia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Calgary
country: Canada
facility: Arthur Je Child Comprehensive Cancer Centre
city: Quebec
country: Canada
facility: Chu de Quebec Universite Laval, Hopital de Lenfant Jesus, Centre Integre de Cancerologie (Cic)
city: Bordeaux
country: France
facility: Centre de Lutte Contre Le Cancer Institut Bergonie
city: Clermontferrand
country: France
facility: Hopital Estaing
city: Creteil
country: France
facility: Chu Henri Mondor
city: Lille
country: France
facility: Hopital Claude Huriez Chu Lille
city: Lyon Cedex
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Montpellier
country: France
facility: Chu Montpellier Hopital Saint Eloi
city: Paris
country: France
facility: Hopital de La Pitie Salpetriere
city: Rouen Cedex
country: France
facility: Centre Henri Becquerel
city: Tbilisi
country: Georgia
facility: Arensia Exploratory Medicine Llc
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus An Der Technischen Universitat Dresden
city: Koln
country: Germany
facility: Uniklinik Koeln (Aoer)
city: Leipzig
country: Germany
facility: Universitares Krebszentrum Leipzig
city: Luebeck
country: Germany
facility: Universitaetsklinikum Schleswig Holstein Campus Luebeck
city: Mainz
country: Germany
facility: Klinikum Johannes Gutenberg Universitaet Mainz
city: Munchen
country: Germany
facility: Klinikum Grosshadern Ludwig Maximilians Universitat Munchen
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Bologna
country: Italy
facility: Policlinico Sorsola Malpighi, Aou Di Bologna
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
city: Milano
country: Italy
facility: Niguarda Cancer Center Division of Hematology
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
city: Verona
country: Italy
facility: Centroricerche Cliniche Di Verona Srl
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital Clinical Oncology
state: Aichi
city: Chibashi
country: Japan
facility: Chiba Cancer Center
state: Chiba
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Kotoku
country: Japan
facility: Cancer Institute Hospital of Jfcr
state: Tokyo
city: YokohamaShi
country: Japan
facility: Yokohama Municipal Citizens Hospital
city: BusanjinGu
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
state: Busan Gwang'yeogsi
city: SeoGu
country: Korea, Republic of
facility: Pusan National University Hospital
state: Busan Gwang'yeogsi
city: GangnamGu
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Teugbyeolsi
city: SeochoGu
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St Marys Hospital
state: Seoul Teugbyeolsi
city: SeodaemunGu
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: SongpaGu
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul Teugbyeolsi
city: Chisinau
country: Moldova, Republic of
facility: The Institute of Oncology, Arensia Exploratory Medicine
city: Barcelona
country: Spain
facility: Hospital Universitario Vall Dhebron
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu I Sant Pau
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Md Anderson Cancer Center Madrid Spain
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Goteborg
country: Sweden
facility: Sahlgrenska University Hospital Hematology
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Solna
city: Uppsala
country: Sweden
facility: Uppsala Akademiska Sjukhus
city: Abidinpaa
country: Turkey
facility: Ankara University
city: Ankara
country: Turkey
facility: Dr Abdurrahman Yurtaslan Research and Training Hospital
city: Balcova
country: Turkey
facility: Dokuz Eylul University
city: Kayseri
country: Turkey
facility: Erciyes University
city: Sakarya
country: Turkey
facility: Sakarya Training and Research Hospital
city: Samsun
country: Turkey
facility: Ondokuz Mayis University
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre
city: Headington
country: United Kingdom
facility: Churchill Hospital Oxford University Hospital Nhs Trust
city: Leeds
country: United Kingdom
facility: St Jamess University Hospital
city: NewCastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals Nhs Trust
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: