A Dose-Escalation and Expansion Study of BGB-16673 in Participants With B-Cell Malignancies

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 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)

Study Overview

• Status: Recruiting
• Conditions: Follicular Lymphoma; Waldenström Macroglobulinemia; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Chronic Lymphocytic Leukemia; Non-Hodgkin Lymphoma; Diffuse Large B Cell Lymphoma; Small Lymphocytic Lymphoma; B-cell Malignancy
• Intervention / Treatment: Drug: BGB-16673

• Study Type: Interventional
• Enrollment (Estimated): 466
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Study Director, MD
• Study Contact Backup: Name: BeiGene; Phone Number: 1.877.828.5568; Email: clinicaltrials@beigene.com

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Recruiting
      • Concord Repatriation General Hospital
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Recruiting
      • St Vincents Hospital Melbourne
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter MacCallum Cancer Centre
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • The Alfred Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • Linear Clinical Research
    • West Perth, Western Australia, Australia, 6005
      • Recruiting
      • Perth Blood Institute
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Recruiting
      • Tom Baker Cancer Center
• France
  • Bordeaux, France, 33076
    • Recruiting
    • Centre de Lutte Contre Le Cancer Institut Bergonie
  • Clermont Ferrand, France, 63003
    • Recruiting
    • Hopital Estaing
  • Creteil, France, 94000
    • Recruiting
    • CHU Henri Mondor
  • Marseille, France, 13009
    • Recruiting
    • Institut Paoli Calmettes
  • Montpellier Cedex, France, 34295
    • Recruiting
    • Chu Montpellier Hopital Saint Eloi
  • Paris, France, 75013
    • Recruiting
    • Hopital de la Pitie Salpetriere
  • Rouen Cedex, France, 76038
    • Recruiting
    • Centre Henri Becquerel
• Georgia
  • Tbilisi, Georgia, 0112
    • Recruiting
    • Arensia Exploratory Medicine Llc
• Germany
  • Ulm, Germany, 89081
    • Recruiting
    • Universitaetsklinikum Ulm, Innere Medizin Iii
• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • Policlinico Sorsola Malpighi, Aou Di Bologna
  • Milano, Italy, 20132
    • Recruiting
    • Ospedale San Raffaele
  • Milano, Italy, 20162
    • Recruiting
    • Niguarda Cancer Center Division of Hematology
  • Verona, Italy, 37134
    • Recruiting
    • Centroricerche Cliniche Di Verona Srl
• Korea, Republic of
  • Busan Gwang'yeogsi
    • Busan, Busan Gwang'yeogsi, Korea, Republic of, 47392
      • Recruiting
      • Inje University Busan Paik Hospital
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03080
      • Recruiting
      • Seoul National University Hospital
• Moldova, Republic of
  • Chisinau, Moldova, Republic of, 2025
    • Recruiting
    • The Institute of Oncology, Arensia Exploratory Medicine
• Spain
  • Barcelona, Spain, 08025
    • Recruiting
    • Hospital de La Santa Creu I Sant Pau
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitario Vall Dhebron
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital General Universitario Gregorio Maranon
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28033
    • Recruiting
    • Md Anderson Cancer Center Madrid Spain
  • Majadahonda, Spain, 28222
    • Recruiting
    • Hospital Universitario Puerta de Hierro Majadahonda
  • Valencia, Spain, 46010
    • Recruiting
    • Hospital Clínico Universitario de Valencia
• Sweden
  • Goteborg, Sweden, 41345
    • Recruiting
    • Sahlgrenska University Hospital Hematology
  • Stockholm, Sweden, 171 76
    • Recruiting
    • Karolinska Universitetssjukhuset Solna
  • Uppsala, Sweden, 75185
    • Recruiting
    • Uppsala Akademiska Sjukhus
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • University of Alabama At Birmingham Hospital
  • Arizona
    • Phoenix, Arizona, United States, 85254
      • Recruiting
      • Mayo Clinic Phoenix
    • Tucson, Arizona, United States, 85724
      • Recruiting
      • University of Arizona Cancer Center
  • California
    • La Jolla, California, United States, 92037
      • Recruiting
      • University of California San Diego (Ucsd) Moores Cancer Center
    • Los Angeles, California, United States, 90067
      • Recruiting
      • Valkyrie Clinical Trials
    • Santa Monica, California, United States, 90404
      • Recruiting
      • UCLA Santa Monica Cancer Care
    • Stanford, California, United States, 94305
      • Recruiting
      • Stanford Medicine
  • Colorado
    • Fort Collins, Colorado, United States, 80528
      • Recruiting
      • Uchealth North
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic Jacksonville
    • Tampa, Florida, United States, 33606
      • Recruiting
      • Tampa General Hospital Cancer Institute
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa Hospitals and Clinics
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Recruiting
      • Norton Cancer Institute Pavilion
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Recruiting
      • Mary Bird Perkins Cancer Center
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Recruiting
      • American Oncology Partners of Maryland Pa
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic Rochester
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • Recruiting
      • Nebraska Cancer Specialists
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Recruiting
      • Comprehensive Cancer Centers of Nevada
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center Mskcc
    • New York, New York, United States, 10021
      • Recruiting
      • Weill Cornell Medical College Newyork Presbyterian Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Recruiting
      • Virginia Commonwealth University Massey Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1a (Monotherapy Dose Escalation); Dose escalation in selected R/R B-Cell malignancies to inform safety, tolerability and MTD.	Drug: BGB-16673; Orally administered
Experimental: Part 1b (Monotherapy Safety Expansion); Additional participants with selected R/R B-Cell malignancies will be enrolled at selected doses to help inform the selection of the recommended phase two dose (RP2D).	Drug: BGB-16673; Orally administered
Experimental: Part 1c (Additional Monotherapy Safety Expansion); After RP2D is determined, additional safety data will be collected to confirm RP2D for participants with selected B-cell malignancies not being evaluated in Part 2	Drug: BGB-16673; Orally administered
Experimental: Part 2 (Monotherapy Expansion); The totality of the data from Part 1a, Part 1b, and Part 1c will be used to further evaluate the safety and efficacy of BGB-16673 at the recommended dose(s) for Phase 2 expansion in specific histologies.	Drug: BGB-16673; Orally administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) with adverse events leading to discontinuation, and Adverse Events (AEs) graded according NCI-CTCAE V5.	TEAE is defined as an AE that had an onset date or a worsening in severity from baseline (pretreatment) on or after the date of the first dose of the study drug and up to 30 days after the last dose of study treatment or the initiation of a new anticancer therapy, whichever is earlier	approximately 3 years
Recommended Phase 2 Dose (RP2D) of BGB-16673	RP2D is the recommended dose for further evaluation in Part 2, determined based on the totality of the available clinical safety, clinical efficacy, pharmacokinetics (PK), and pharmacodynamic data in Part 1.	approximately 3 years
Maximum Tolerated Dose (MTD) of BGB-16673	determined by the sponsor based on the Safety Monitoring Committee's recommendation considering the totality of the available clinical safety, clinical efficacy, pharmacokinetics (PK), and pharmacodynamic data	approximately 3 years
Phase 2: Overall response rate (ORR)	Cohort specific ORRs based on best overall response of partial response (PR) or better as assessed by Independent Review Committee (IRC) for prticipants in cohorts 1 and 2; by investigator for other cohorts.	approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Single Dose Maximum observed plasma concentration (Cmax) of BGB-16673	Collected for both Part 1 and Part 2	Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Single Dose Minimum observed plasma concentration (Cmin) of BGB-16673	Collected for both Part 1 and Part 2	Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Single Dose Time to reach Cmax (tmax) of BGB-16673	Collected for both Part 1 and Part 2	Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Single Dose Time to reach half of Cmax (T1/2) of BGB-16673	Collected for both Part 1 and Part 2	Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Single Dose Area under the plasma concentration-time curve (AUC) of BGB-16673	Collected for both Part 1 and Part 2	Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Single Dose apparent total clearance of drug from plasma after oral administration (CL/F) of BGB-16673	Collected for both Part 1 and Part 2	Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Single Dose apparent volume of distribution (Vz/F) of BGB-16673	Collected for both Part 1 and Part 2	Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Single Dose accumulation ratios of BGB-16673	Collected for both Part 1 and Part 2	Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Steady State Maximum observed plasma concentration (Cmax) of BGB-16673	Collected for both Part 1 and Part 2	Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Steady State minimum observed plasma concentration (Cmin) of BGB-16673	Collected for both Part 1 and Part 2	Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Steady State Time to reach Cmax (tmax) of BGB-16673	Collected for both Part 1 and Part 2	Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Steady State Time to reach half of Cmax (T1/2) of BGB-16673	Collected for both Part 1 and Part 2	Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Steady State Area under the plasma concentration-time curve (AUC) of BGB-16673	Collected for both Part 1 and Part 2	Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Steady State apparent total clearance of drug from plasma after oral administration (CL/F) of BGB-16673	Collected for both Part 1 and Part 2	Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Steady State apparent volume of distribution (Vz/F) of BGB-16673	Collected for both Part 1 and Part 2	Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Bruton's tyrosine kinase (BTK) protein degradation in peripheral blood after BGB-16673 monotherapy	Collected for both Part 1 and Part 2	Day 1 pre-dose and 8 hours post-dose (approximately 2 years)
Phase 1: Overall response rate (ORR)	defined as the proportion of participants whose best overall response is better than stable disease.	approximately 3 years
Phase 1: Number of Waldenström Macroglobulinemia (WM) Participants with major response rate (MRR)	MRR is defined as the proportion of participants whose best overall response (BOR) is partial response (PR) or better (PR, very good partial response (VGPR), or complete response (CR)).	approximately 3 years
Phase 2: Duration of Response (DOR)	DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first as assessed by the investigator and the IRC.	approximately 3 years
Phase 2: Time to Response (TTR)	TTR is defined as the time from study treatment start to date of the earliest qualifying response (partial response or better), as assessed by IRC and the investigator	approximately 3 years
Phase 2: Progression- Free Survival (PFS)	PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by IRC and the investigator	approximately 3 years
Phase 2: Overall Survival (OS)	OS is defined as the time from first study drug administration to the date of death due to any cause	approximately 3 years
Phase 2 (Cohort 1): Best Overall Response (BOR) of partial response with lymphocytosis or better	Best overall response is defined as the best response recorded from the first dose of the study drug until the data cutoff date or initiation of a new anticancer treatment, whichever occurs first. As determined by IRC and investigators.	approximately 3 years
Phase 2 (Cohort 3): BOR of minor response or better		approximately 3 years
Phase 2 (Cohort 1): Participant-reported outcomes (PRO) via Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionarre	FACT-Leu is a PRO questionnaire that is developed to measure disease-specific symptoms and/or treatment-related concerns in participants with leukemia (Cela et al. 2012). It has been linguistically validated in over 50 languages, and frequently to measure HRQoL in chronic lymphocytic leukemia (CLL) participants. The questionnaire is comprised of 44 questions and 5 subscales including Physical Well-being (7 items), Social / Family Well-being (7 items), Emotional Well-being (6 items), Functional Wellbeing (7 items), and 17 single items under Additional Concerns).	approximately 3 years
Phase 2 (Cohort 2): Participant-reported outcomes (PRO) via National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lymphoma Cancer Symptom Index - 18 (NFLymSI-18)	The NFlymSI-18 is a participant-reported outcome questionnaire that is developed to measure disease-specific symptoms and/or treatment-related concerns in participants with advanced lymphoma	approximately 3 years

Collaborators and Investigators

• Sponsor: BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2021
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: August 9, 2021
• First Submitted That Met QC Criteria: August 9, 2021
• First Posted (Actual): August 16, 2021

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Disease Attributes; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Leukemia, Lymphoid; Leukemia; Leukemia, B-Cell; Lymphoma, B-Cell; Chronic Disease; Neoplasms; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Waldenstrom Macroglobulinemia; Leukemia, Lymphocytic, Chronic, B-Cell
• Other Study ID Numbers: BGB-16673-101; 2022-502157-33-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No