This study has been transitioned to CTIS with ID 2024-511267-28-00 check the CTIS register for the current data. To evaluate the long-term safety of zanubrutinib in patients with B-cell cancers who participated in a BeiGene parent study for…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoints:
* The primary endpoint of the study is safety as assessed by incidence of all
treatment-emergent AEs and SAEs
Secondary outcome
Secondary Endpoints:
* Progression-free survival (PFS) per investigator assessment
* Duration of response (DOR) per investigator assessment
* Overall survival (OS)
Background summary
This is an open-label, multi-center, LTE study to evaluate the long-term safety
and efficacy of zanubrutinib in patients with B-cell cancers who are or were
previously enrolled in a BeiGene parent study and who are still benefiting or
may benefit from treatment with zanubrutinib, or who are willing to have
long-term survival follow-up. Zanubrutinib (also known as BGB-3111) is a
second-generation small-molecule oral Bruton tyrosine kinase (BTK) inhibitor,
which forms an irreversible covalent bond at Cys481 within the adenosine
triphosphate binding pocket of the BTK protein. BTK is a member of the tyrosine
kinase expressed in hepatocellular carcinoma (TEC) family of tyrosine protein
kinases and is critical in the B-cell receptor signalling cascade. As a central
component to the B-cell receptor signalling pathway, BTK is involved in B-cell
growth, maturation, differentiation, proliferation, migration, and adhesion.
Constitutive activation of B-cell receptor signalling is critical for cell
survival and clonal expansion in many B-cell cancers. Genetic BTK defects cause
B-cell immunodeficiency and hypogammaglobulinaemia/ agammaglobulinaemia (Seiler
and Dreyling 2017). Inhibition of BTK has emerged as a promising strategy for
targeting MCL, WM and other B-cell cancers, such as chronic lymphocytic
leukaemia (CLL), small lymphocytic lymphoma (SLL), follicular lymphoma, and
diffuse large B-cell lymphoma (DLBCL) (Rickert 2013). Zanubrutinib is a novel,
oral, second-generation BTK inhibitor designed to be more selective and have
more favourable pharmacokinetic (PK) and pharmacodynamic (PD) properties than
the approved first-in-class BTK inhibitor ibrutinib (IMBRUVICA Product
Monograph 2020) which has demonstrated a high level of clinical activity across
a range of B-cell cancers (Burger et al 2015; Byrd et al 2015; Treon et al
2015a; Wang et al 2015). When inhibiting BTK, neoplastic B cells will not
proliferate, survive or adhere to the bone marrow. Zanubrutinib displays great
potency and BTK selectivity to treat B-cell cancers.
Study objective
This study has been transitioned to CTIS with ID 2024-511267-28-00 check the CTIS register for the current data.
To evaluate the long-term safety of zanubrutinib in patients with B-cell
cancers who participated in a BeiGene parent study for zanubrutinib
Study design
This is an open-label, multi-center, long-term extension (LTE) study to
evaluate the long-term safety and efficacy of zanubrutinib in patients with
B-cell cancers who are or were previously enrolled in a BeiGene parent study
and who are still benefiting or may benefit from treatment with zanubrutinib,
or who are willing to have long-term survival follow-up.
Scenarios of patients from BeiGene parent studies for potential enrollment in
this LTE study are detailed in Protocol (Section 4 for Eligibility Criteria (in
particular, Inclusion Criteria 1 and 2)). They include, but are not limited to,
the following:
- At the time of final analysis or study closure of the eligible BeiGene parent
study
- After occurrence of progressive disease (PD) on zanubrutinib or non-BTK
inhibitor drug(s)
(under certain circumstances)
Patients may transfer to this study at alternative timepoints for alternative
reasons after discussion with and approval by the medical monitor.
Patients who are only being followed for survival in the eligible BeiGene
parent study should enroll in this LTE study for continued survival follow-up.
Patients who are in survival follow-up after permanent discontinuation of
comparator drug(s) can be considered for zanubrutinib treatment in this study
unless they have a history of PD while receiving a BTK inhibitor (excluding
zanubrutinib).
Patients who will enroll in this study only for long-term survival follow-up
(ie, will not receive zanubrutinib on this study) will directly proceed with
survival follow-up assessments. after eligibility has been confirmed; no
assessments are required for eligibility confirmation.
All patients must sign a new informed consent form for this study.
A treatment cycle for zanubrutinib consists of 28 days.
- The starting dose of zanubrutinib for patients with prior zanubrutinib
treatment should be
equivalent to the last dose level received in the BeiGene parent study.
- Zanubrutinib-naive patients (ie, eligible patients who will receive
zanubrutinib for the first time) will receive a standard dose of 320 mg once
daily or 160 mg twice daily (for a total daily dose of 320 mg zanubrutinib).
Efficacy assessments will be conducted at a minimum of every 6 months (± 14
days) per investigator discretion.
Patients who are receiving zanubrutinib in this study will continue to receive
zanubrutinib until PD, unacceptable toxicity, death, start of new
antineoplastic therapy, withdrawal of consent, lost to follow-up, or study
termination by the sponsor, whichever occurs first. Blood samples will be
obtained at Screening and at the time of PD for biomarker analysis purposes.
Patients who are continuing to receive benefit from monotherapy after PD, based
on the investigator*s assessment, may remain on monotherapy after discussion
with and approval by the medical monitor or designee. These patients who remain
in the study will continue to follow the required assessments during the
Treatment Phase.
All patients who permanently discontinue study drug will have a Safety
Follow-up Visit approximately 30 days after the last dose of study drug or
before the initiation of new antineoplastic therapy, whichever occurs first.
Patients will be followed with efficacy assessments (if applicable), for
further antineoplastic therapy, and for survival every 6 months (± 14 days)
according to the Treatment Phase schedule.
Intervention
NA
Study burden and risks
All safety information collected so far from all sources has been reviewed and
evaluated by BeiGene. The significance of these data has been evaluated taking
into consideration the cumulative experience and overall patient exposure to
zanubrutinib. The benefits and risks (safety experience) of treatment with
zanubrutinib have been assessed based on both clinical trials and
post-marketing experience and overall indicate a positive benefit-risk profile
for zanubrutinib. BeiGene considers that the benefit-risk profile for
zanubrutinib in the currently approved indications continues to remain
favorable. As demonstrated by clinical data obtained to date, zanubrutinib is a
highly selective and orally bioavailable BTK inhibitor that not only achieves
high systemic exposure for complete BTK occupancy in the blood and lymph nodes,
it also remains highly tolerable, despite its exposure and occupancy
advantages. Extent of exposure to study drug will be summarized descriptively
as duration of exposure (days), cumulative total dose received per patient
(mg), dose intensity (mg/day) and relative dose intensity, on the BeiGene
parent study, this current study, and the total exposure across both studies.
Aeschengraben 27 Aeschengraben 27
Basel 4051
NL
Aeschengraben 27 Aeschengraben 27
Basel 4051
NL
Listed location countries
Age
Inclusion criteria
Inclusion Criteria for Patients in Treatment Phase
Each patient eligible to participate in the Treatment Phase of this study must
meet all applicable
criteria:
1. As part of a BeiGene-sponsored parent study:
a. Currently participating, or
b. Participated recently
2. Intent to continue or start zanubrutinib treatment after occurrence of any
of the following:
a. At time of final analysis or study closure of the eligible BeiGene-sponsored
parent study:
* For zanubrutinib-naive patients, rationale for initiation of zanubrutinib
treatment must be discussed with and approved by the medical monitor
b. At time of progressive disease (PD) after occurrence of either of the
following:
i Patient was receiving zanubrutinib at the time of progressive disease (PD),
and the investigator and patient agree it is in the patient*s best interest to
continue zanubrutinib ((following discussion with the medical
monitor or designee of the parent study and this study)
*The following signs and symptoms may be indicators of non-clinically
significant progression warranting continued use of zanubrutinib despite
radiologic progression: absence of clinical symptoms and signs of
disease progression (including clinically significant worsening of
laboratory values), stable Eastern Cooperative Oncology Group
Performance Scale (ECOG PS), absence of rapid progression of disease
or of progressive tumor at critical anatomical sites that requires urgent
alternative medical intervention. In these scenarios, investigators must inform
patients that continuing treatment is not considered standard in the treatment
of cancer but that in the opinion of the investigator, the
patient will continue to benefit from zanubrutinib.)
ii Patient was receiving a non-BTK inhibitor drug at the time of progressive
disease (PD), and the investigator and patient agree that the patient may
clinically benefit from zanubrutinib treatment (following discussion with the
medical
monitor or designee of the parent study and this study)
c. At an alternative timepoint for an alternative reason not described in
Inclusion Criteria 2a and 2b (following discussion with the medical monitor or
designee)
3. Patient who is currently on zanubrutinib treatment:
Does not meet any criteria in Section 6.1.3 for zanubrutinib hold or permanent
discontinuation, and, in the opinion of the investigator, will continue to
benefit from
zanubrutinib treatment
* If patient meets Section 6.1.3 criteria but both investigator and patient
agree it
is in the patient*s best interest to continue zanubrutinib, patient may be
eligible after discussion with and approval by the medical monitor
* Patient who is receiving zanubrutinib in combination with standard-of-care
drug(s): Only has to meet criteria for continued zanubrutinib treatment to be
eligible. Continued treatment with standard-of-care drug(s) is determined by
applicable prescribing information
4. Zanubrutinib-naive patient who either is currently participating in a
BeiGene parent study
or recently participated in a BeiGene parent study:
Must meet the following criteria <= 15 days before first dose of study drug:
a. Platelets >= 50,000/mm3
b. Absolute neutrophil count >= 750/mm3
c. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 3 x
upper
limit of normal
d. Serum total bilirubin <= 3 x upper limit of normal (not required for cases
with
documented Gilbert Syndrome)
e. QT interval corrected for heart rate using Fridericia*s formula (QTcF) <= 480
msec;
site to provide copy of ECG tracing and rhythm
f. No known New York Heart Association (NYHA) Class III or IV congestive heart
failure (see Appendix 2 for NYHA criteria)
g. Creatinine clearance >= 30 mL/min (as estimated by the Cockcroft-Gault
equation
based on ideal body weight or estimated glomerular filtration rate [eGFR] from
the
Modification of Diet in Renal Disease [MDRD])
5. Female patients of childbearing potential must be willing to use a highly
effective method
of birth control initiated before first dose of study drug, for the duration of
the study, and
for >= 90 days after last dose of zanubrutinib (see Appendix 3 for the
definition of
childbearing potential and highly effective methods of birth control)
6. Nonsterile males must be willing to use a highly effective method of birth
control for the
duration of the study, and for >= 90 days after last dose of zanubrutinib (see
Appendix 3
for the definition of sterile male and highly effective methods of birth
control)
7. Written informed consent
Inclusion Criteria for Patients in Survival Follow-up
Each patient eligible to participate in survival follow-up of this study must
meet all the following
criteria:
1. Currently enrolled in an eligible BeiGene parent study in survival follow-up
and will not
be treated with zanubrutinib in this study
2. Written informed consent
Exclusion criteria
Exclusion Criteria for Patients in Treatment Phase
Each patient eligible to participate in the Treatment Phase of this study must
not meet any of the
following exclusion criteria:
1. Permanently discontinued from zanubrutinib treatment in the
BeiGene-sponsored parent study due
to unacceptable toxicity, noncompliance with study procedures, or withdrawal of
consent
2. Uncontrolled active systemic infection or recent infection requiring
parenteral antimicrobial
therapy
3. Life-threatening illness, medical condition, or organ system dysfunction
which, in the
investigator's opinion, could compromise the patient's safety, interfere with
the
absorption or metabolism of zanubrutinib, or put the study outcomes at undue
risk
4. Concomitant chemotherapy, targeted therapy, radiation therapy,
antibody-based therapy,
or any prohibited concomitant therapy outlined in the protocol
5. Pregnant or lactating woman
6. Inability to comply with study procedures
7. Concurrent participation in another therapeutic clinical study
8. History of progressive disease (PD) while receiving a BTK inhibitor
(excluding
zanubrutinib)
9. Vaccination with a live vaccine within 35 days prior to first dose of study
drug
Exclusion Criteria for Patients in Survival Follow-up
Each patient eligible to participate in survival follow-up of this study must
not meet any of the
following exclusion criteria:
1. Permanently discontinued from the BeiGene parent study
2. Inability to comply with requests for survival follow-up
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | BGB-3111-LTE1 |
| EU-CTR | CTIS2024-511267-28-00 |
| EudraCT | EUCTR2020-000547031-NL |
| CCMO | NL77947.041.21 |