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

Chronic Lymphocytic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05006716
• Other study ID #: BGB-16673-101
• Secondary ID: 2022-502157-33-0
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 13, 2021
• Est. completion date: September 30, 2027

Study information

• Verified date: April 2024
• Source: BeiGene
• Contact: BeiGene
• Phone: 1.877.828.5568
• Email: clinicaltrials[@]beigene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 466
• Est. completion date: September 30, 2027
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• B-cell Malignancy
• Chronic Lymphocytic Leukemia
• Diffuse Large B Cell Lymphoma
• Follicular Lymphoma
• Leukemia, Lymphocytic, Chronic, B-Cell
• Lymphoma
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma
• Marginal Zone Lymphoma
• Neoplasms
• Non-Hodgkin Lymphoma
• Small Lymphocytic Lymphoma
• Waldenstrom Macroglobulinemia
• Waldenström Macroglobulinemia

Intervention

Drug:
• BGB-16673
Orally administered

Locations

Country	Name	City	State
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	Perth Blood Institute	West Perth	Western Australia
Canada	Tom Baker Cancer Center	Calgary	Alberta
France	Centre de Lutte Contre Le Cancer Institut Bergonie	Bordeaux
France	Hopital Estaing	Clermont Ferrand
France	Chu Henri Mondor	Creteil
France	Institut Paoli Calmettes	Marseille
France	Chu Montpellier Hopital Saint Eloi	Montpellier Cedex
France	Hopital de La Pitie Salpetriere	Paris
France	Centre Henri Becquerel	Rouen Cedex
Georgia	Arensia Exploratory Medicine Llc	Tbilisi
Germany	Universitaetsklinikum Ulm, Innere Medizin Iii	Ulm
Italy	Policlinico Sorsola Malpighi, Aou Di Bologna	Bologna
Italy	Niguarda Cancer Center Division of Hematology	Milano
Italy	Ospedale San Raffaele	Milano
Italy	Centroricerche Cliniche Di Verona Srl	Verona
Korea, Republic of	Inje University Busan Paik Hospital	Busan	Busan Gwang'yeogsi
Korea, Republic of	Seoul National University Hospital	Seoul	Seoul Teugbyeolsi
Moldova, Republic of	The Institute of Oncology, Arensia Exploratory Medicine	Chisinau
Spain	Hospital de La Santa Creu I Sant Pau	Barcelona
Spain	Hospital Universitario Vall Dhebron	Barcelona
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Md Anderson Cancer Center Madrid Spain	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda
Spain	Hospital Clinico Universitario de Valencia	Valencia
Sweden	Sahlgrenska University Hospital Hematology	Goteborg
Sweden	Karolinska Universitetssjukhuset Solna	Stockholm
Sweden	Uppsala Akademiska Sjukhus	Uppsala
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	American Oncology Partners of Maryland Pa	Bethesda	Maryland
United States	University of Alabama At Birmingham Hospital	Birmingham	Alabama
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Uchealth North	Fort Collins	Colorado
United States	Nebraska Cancer Specialists	Grand Island	Nebraska
United States	Md Anderson Cancer Center	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	University of California San Diego (Ucsd) Moores Cancer Center	La Jolla	California
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Valkyrie Clinical Trials	Los Angeles	California
United States	Norton Cancer Institute Pavilion	Louisville	Kentucky
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center Mskcc	New York	New York
United States	Weill Cornell Medical College Newyork Presbyterian Hospital	New York	New York
United States	Mayo Clinic Phoenix	Phoenix	Arizona
United States	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	UCLA Santa Monica Cancer Care	Santa Monica	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Stanford Medicine	Stanford	California
United States	Tampa General Hospital Cancer Institute	Tampa	Florida
United States	University of Arizona Cancer Center	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Georgia,  Germany,  Italy,  Korea, Republic of,  Moldova, Republic of,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Phase 1: Overall response rate (ORR)	defined as the proportion of participants whose best overall response is better than stable disease.	approximately 3 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Phase 2 (Cohort 3): BOR of minor response or better		approximately 3 years
Secondary	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
Secondary	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