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: May 12, 2022
• Sponsor: BeiGene
• Information provided by (Responsible Party): BeiGene

Tracking Information

• First Submitted Date: August 9, 2021
• First Posted Date: August 16, 2021
• Last Update Posted Date: May 12, 2022
• Actual Study Start Date: September 13, 2021
• Estimated Primary Completion Date: May 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 9, 2021)

• 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 ]
  also may be assessed using the 2018 iwCLL Guidelines for Diagnosis, Indications for Treatment, Response Assessment, and Supportive Management of CLLA. 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
• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 9, 2021)

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• BTK protein degradation in peripheral blood upon BGB-16673 monotherapy [ Time Frame: Day 1 pre-dose and 8 hours post-dose (approximately 2 years) ]
• Number of Participants with overall response rate (ORR) [ Time Frame: approximately 3 years ]
  Best overall response is defined as the best response recorded from the first dose of the study drug until data cut or the initiation of a new anticancer treatment
• Number of WM Participants with major response rate (MRR) [ 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)).

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 1 Dose-Escalation and Expansion Study of BGB-16673 in Patients With B-Cell Malignancies
• 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
• Brief Summary: Study consists of two parts to explore BGB-16673 recommended dosing, a part 1 monotherapy dose finding and a part 2 (cohort expansion in two cohorts)
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• B-cell Malignancy
• Marginal Zone Lymphoma
• Follicular Lymphoma
• Non-hodgkin Lymphoma
• Waldenström Macroglobulinemia

Intervention

Drug: BGB-16673

BGB-16673 doses are to be administered as a once daily regimen

Study Arms

• Experimental: Part 1 Monotherapy Dose Finding
  BGB-16673
  Intervention: Drug: BGB-16673
• Experimental: Part 2 Expansion Cohorts
  BGB-11673 for two expansion cohorts
  Intervention: Drug: BGB-16673

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 9, 2021): 76
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 30, 2025
• Estimated Primary Completion Date: May 30, 2024 (Final data collection date for primary outcome measure)

Eligibility 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, FL, MCL, CLL/SLL, or WM.
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.
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; patients with CLL/SLL or MCL enrolling in the expansion cohorts 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, or

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: BeiGene; 1.877.828.5568; clinicaltrials@beigene.com

Contact: Study Director, MD

• Listed Location Countries: Australia, United States

Administrative Information

• NCT Number: NCT05006716
• Other Study ID Numbers: BGB-16673-101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes

• Responsible Party: BeiGene
• Study Sponsor: BeiGene
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: BeiGene
• Verification Date: May 2022