A Phase 1 Dose-Escalation and Expansion Study of BGB-16673 in Patients With B-Cell Malignancies

• ClinicalTrials.gov Identifier: NCT05006716
• Recruitment Status: Recruiting
• First Posted: August 16, 2021
• Last Update Posted: January 18, 2023
• Sponsor: BeiGene
• Information provided by (Responsible Party): BeiGene

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
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	Drug: BGB-16673	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 232 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Open-Label, Dose-Escalation and -Expansion Study of the Bruton Tyrosine Kinase-Targeted Protein-Degrader BGB-16673 in Patients With B-Cell Malignancies
• Actual Study Start Date: September 13, 2021
• Estimated Primary Completion Date: September 30, 2024
• Estimated Study Completion Date: September 30, 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: Single Arm; Part 1: BGB-16673 for Monotherapy Dose Finding Part 2: BGB-16673 Two Expansion Cohorts	Drug: BGB-16673; BGB-16673 doses are to be administered as a once daily regimen

Outcome Measures

Primary Outcome Measures :

1. Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) with adverse events leading to discontinuation, and AEs graded according NCI-CTCAE V5. [ Time Frame: approximately 3 years ]
   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
2. Recommended Phase 2 Dose (RP2D) of Orally Administered BGB-16673 [ Time Frame: approximately 3 years ]
   The RP2D is the maximum tolerated dose (MTD) or less. An RP2D less than the MTD may be chosen if aspects of tolerability or efficacy not encompassed by the MTD determination suggest utilizing a lower dose

Secondary Outcome Measures :

1. Single Dose Maximum observed plasma concentration (Cmax) of BGB-16673 [ Time Frame: Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years) ]
   Collected for both Part 1 and Part 2
2. Single Dose Minimum observed plasma concentration (Cmin) of BGB-16673 [ Time Frame: Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years) ]
   Collected for both Part 1 and Part 2
3. Single Dose Time to reach Cmax (tmax) of BGB-16673 [ Time Frame: Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years) ]
   Collected for both Part 1 and Part 2
4. Single Dose Time to reach half of Cmax (T1/2) of BGB-16673 [ Time Frame: Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years) ]
   Collected for both Part 1 and Part 2
5. Single Dose Area under the plasma concentration-time curve (AUC) of BGB-16673 [ Time Frame: Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years) ]
   Collected for both Part 1 and Part 2
6. Single Dose apparent total clearance of drug from plasma after oral administration (CL/F) of BGB-16673 [ Time Frame: Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years) ]
   Collected for both Part 1 and Part 2
7. Single Dose apparent volume of distribution (Vz/F) of BGB-16673 [ Time Frame: Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years) ]
   Collected for both Part 1 and Part 2
8. Single Dose accumulation ratios of BGB-16673 [ Time Frame: Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years) ]
   Collected for both Part 1 and Part 2
9. Steady State Maximum observed plasma concentration (Cmax) of BGB-16673 [ Time Frame: Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years) ]
   Collected for both Part 1 and Part 2
10. Steady State minimum observed plasma concentration (Cmin) of BGB-16673 [ Time Frame: Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years) ]
    Collected for both Part 1 and Part 2
11. Steady State Time to reach Cmax (tmax) of BGB-16673 [ Time Frame: Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years) ]
    Collected for both Part 1 and Part 2
12. Steady State Time to reach half of Cmax (T1/2) of BGB-16673 [ Time Frame: Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years) ]
    Collected for both Part 1 and Part 2
13. Steady State Area under the plasma concentration-time curve (AUC) of BGB-16673 [ Time Frame: Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years) ]
    Collected for both Part 1 and Part 2
14. Steady State apparent total clearance of drug from plasma after oral administration (CL/F) of BGB-16673 [ Time Frame: Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years) ]
    Collected for both Part 1 and Part 2
15. Steady State apparent volume of distribution (Vz/F) of BGB-16673 [ Time Frame: Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years) ]
    Collected for both Part 1 and Part 2
16. BTK protein degradation in peripheral blood upon BGB-16673 monotherapy [ Time Frame: Day 1 pre-dose and 8 hours post-dose (approximately 2 years) ]
17. Number of Participants with overall response rate (ORR) [ Time Frame: approximately 3 years ]
    defined as the proportion of patients whose best overall response is better than stable disease.
18. Number of WM Participants with major response rate (MRR) in Waldenström's macroglobulinemia patients, [ Time Frame: approximately 3 years ]
    MRR is defined as the proportion of patients whose best overall response (BOR) is partial response (PR) or better (PR, very good partial response [VGPR], or complete response (CR)).

Eligibility Criteria

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

Criteria

Inclusion Criteria :

1. Provision of signed and dated written informed consent prior to any study-specific procedures, sampling, or data collection
2. Age ≥ 18 years
3. Confirmed diagnosis (per World Health Organization [WHO] guidelines, unless otherwise noted) of one of the following: MZL (Part 1a and 1b only), FL (Part 1a only), MCL, CLL/SLL, WM (Part 1a and 1b only), DLBCL (Part 1a only), or >2 treatments per the Richter's transformation to DLBCL (Part 1a only).
4. Patients who have previously received a covalently-binding BTK inhibitor in any line of therapy must have received treatment with the BTK inhibitor for ≥ 8 weeks (unless reason for discontinuation is intolerance).
5. For dose-finding and dose-expansion, patients 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.
6. Measurable disease by radiographic assessment or serum IgM level (WM only)
7. ECOG Performance Status of 0 to 2
8. Patients 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; patients with CLL/SLL or MCL enrolling in the expansion cohorts (Part 2) must have been treated with a BTKi in a prior line of therapy.

Exclusion Criteria:

1. Prior malignancy (other than the disease under study) within the past 2 years, except for curatively treated basal or squamous skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score ≤ 6 prostate cancer
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 patient 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, 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 Richter's transformation of an indolent lymphoma to an aggressive histology (only patients with Richter Transformation to DLBCL are eligible for Part 1a).

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

Contacts and Locations

Contacts

Contact: BeiGene; 1.877.828.5568; clinicaltrials@beigene.com

Contact: Study Director, MD

Locations

United States, Arizona

Mayo Clinic (Phoenix); Recruiting

Phoenix, Arizona, United States, 85004

The University of Arizona Cancer Center; Recruiting

Tucson, Arizona, United States, 85724-5024

United States, California

UCLA Santa Monica Cancer Care; Recruiting

Santa Monica, California, United States, 90404

United States, Florida

Mayo Clinic (Jacksonville); Recruiting

Jacksonville, Florida, United States, 32224

United States, Kentucky

Norton Cancer Institute, St. Matthews Campus; Recruiting

Louisville, Kentucky, United States, 40207

United States, Minnesota

Mayo Clinic (Rochester); Recruiting

Rochester, Minnesota, United States, 55905

United States, New York

Memorial Sloan Kettering Cancer Center; Recruiting

New York, New York, United States, 10065

Weill Cornell Medicine; Recruiting

New York, New York, United States, 10065

United States, Texas

The University of Texas, MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Australia, New South Wales

Concord Repatriation General Hospital; Recruiting

Concord, New South Wales, Australia, 2139

Australia, Victoria

St. Vincent's Hospital Melbourne; Recruiting

Fitzroy, Victoria, Australia, 3065

Peter MacCallum Cancer Institute; Recruiting

Melbourne, Victoria, Australia, 3000

The Alfred Hospital; Recruiting

Melbourne, Victoria, Australia, 3004

Australia, Western Australia

Perth Blood Institute; Recruiting

West Perth, Western Australia, Australia, 6005

Australia

Linear Clinical Research; Recruiting

Nedlands, Australia, 6009

Sponsors and Collaborators

BeiGene

More Information

• Responsible Party: BeiGene
• ClinicalTrials.gov Identifier: NCT05006716
• Other Study ID Numbers: BGB-16673-101; 2022-502157-33-00 ( Other Identifier: EU CT Number )
• First Posted: August 16, 2021
• Last Update Posted: January 18, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

• 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

Additional relevant MeSH terms:

Lymphoma; Neoplasms; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Waldenstrom Macroglobulinemia; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Leukemia, Lymphoid; Leukemia; Lymphoma, B-Cell; Leukemia, B-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders