A Phase 1 Dose-Escalation and Expansion Study of BGB-16673 in Patients With B-Cell Malignancies
Study Details
Study Description
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)
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1 Monotherapy Dose Finding BGB-16673 |
Drug: BGB-16673
BGB-16673 doses are to be administered as a once daily regimen
|
| Experimental: Part 2 Expansion Cohorts BGB-11673 for two expansion cohorts |
Drug: BGB-16673
BGB-16673 doses are to be administered as a once daily regimen
|
Outcome Measures
Primary Outcome Measures
- 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. [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 [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
- Single Dose Maximum observed plasma concentration (Cmax) of BGB-16673 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [Day 1 pre-dose and 8 hours post-dose (approximately 2 years)]
- Number of Participants with overall response rate (ORR) [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) [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
Criteria
Inclusion Criteria:
-
Provision of signed and dated written informed consent prior to any study-specific procedures, sampling, or data collection
-
Age ≥ 18 years
-
Confirmed diagnosis (per World Health Organization [WHO] guidelines, unless otherwise noted) of one of the following: MZL, FL, MCL, CLL/SLL, or WM.
-
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.
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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.
-
Measurable disease by radiographic assessment or serum IgM level (WM only)
-
ECOG Performance Status of 0 to 2
-
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:
-
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
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Requires ongoing systemic treatment for any other malignancy
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Requires ongoing systemic (defined as ≥ 10 mg/day of prednisone or equivalent) corticosteroid treatment.
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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
-
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 history of or currently suspected Richter's transformation.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The University of Arizona Cancer Center | Tucson | Arizona | United States | 85724-5024 |
| 2 | Norton Cancer Institute, St. Matthews Campus | Louisville | Kentucky | United States | 40207 |
| 3 | The University of Texas, MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 4 | Concord Repatriation General Hospital | Concord | New South Wales | Australia | 2139 |
| 5 | Peter MacCallum Cancer Institute | Melbourne | Victoria | Australia | 3000 |
| 6 | The Alfred Hospital | Melbourne | Victoria | Australia | 3004 |
| 7 | Perth Blood Institute | West Perth | Western Australia | Australia | 6005 |
| 8 | Linear Clinical Research | Nedlands | Australia | 6009 |
Sponsors and Collaborators
- BeiGene
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BGB-16673-101