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

Cancer Categories

Hematologic (Blood Cancers)

Karmanos Trial ID

2023-094

NCT ID

NCT05006716

Age Group

Adult

Scope

National

Phase

Phase I/II

Principal Investigator

Dipenkumar
Modi, M.D.
Oncology - Hematology, Oncology - Medical View Profile

Objective:

BGB-16673 Monotherapy Dose Finding (Phase 1)

Primary Objectives:

To evaluate the safety and tolerability of BGB-16673 monotherapy
To define the maximum tolerated dose (or maximum assessed dose) and the
recommended Phase 2 dose (RP2D) of BGB-16673

Secondary Objectives:

To characterize the pharmacokinetic profile of BGB-16673 as monotherapy
To characterize the pharmacodynamic profile of BGB-16673 in peripheral blood
To characterize the preliminary antitumor activity of BGB-16673 monotherapy

BGB-16673 Monotherapy (Phase 2)

Primary Objectives:

To evaluate the antitumor activity of BGB-16673 monotherapy in patients with
relapsed/refractory (R/R) mantle cell lymphoma (MCL) based on overall response
rate (ORR) as assessed by an Independent Review Committee (IRC)
To evaluate the antitumor activity of BGB-16673 monotherapy in patients with R/R
CLL/SLL based on ORR as assessed by investigators

Secondary Objectives:

To evaluate the safety and tolerability of BGB-16673 monotherapy
To further characterize the pharmacokinetic profile of BGB-16673
To further characterize the pharmacodynamic profile of BGB-16673 in peripheral
blood
Patients with R/R MCL:
- To evaluate the antitumor activity of BGB-16673 monotherapy based on ORR as
  assessed by investigators
- To evaluate the antitumor activity of BGB-16673 monotherapy based on best
  overall response (BOR), time to response (TTR), duration of response (DOR), and
  progression-free survival (PFS) as assessed by the IRC and investigators
- To characterize overall survival
- To measure patient-reported outcomes (PRO) in R/R MCL patients via National
  Comprehensive Cancer Network Functional Assessment of Cancer Therapy –
  Lymphoma System Index-18 (NFLymSI-18)
Patients with R/R CLL/SLL:
- To evaluate the antitumor activity of BGB-16673 monotherapy based on ORR,
  DOR, TTR, and PFS as assessed by investigators
- To characterize overall survival

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Eligibility

Inclusion Criteria:

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.
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).
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.
Measurable disease by radiographic assessment or serum IgM level (WM only)
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
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:

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.
Requires ongoing systemic treatment for any other malignancy
Requires ongoing systemic (defined as ≥ 10 mg/day of prednisone or equivalent) corticosteroid treatment.
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
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).

Locations

Karmanos Cancer Institute - Detroit Headquarters

4100 John R
Detroit, MI 48201
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Phone: 800-527-6266

Karmanos Cancer Institute at Weisberg Cancer Center - Farmington Hills

31995 Northwestern Hwy
Farmington Hills, MI 48334
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Phone: 800-527-6266

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