A Phase 1, Dose Escalation, and Cohort Expansion Study Evaluating NX-5948, a Bruton*s Tyrosine Kinase (BTK) Degrader, in Adults with Relapsed/Refractory B-cell Malignancies
- Conditions
- B-cell lymphomasblood cancer10025320
- Registration Number
- NL-OMON54003
- Lead Sponsor
- urix Therapeutics, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 40
- Patients must be >= 18 years of age, and mentally competent
Patients in Phase 1a (Dose Escalation) must have 1 of the following
histologically confirmed R/R B-cell malignancies: R/R CLL, SLL, DLBCL of the
following subgroups: DLBCL, not otherwise specified (NOS), geminal center
B-cell type, activated B-cell type (includes transformed indolent lymphoma
[eg, grade 3b/transformed FL] and Richter-transformed DLBCL, high-grade B-cell
lymphoma (HGBL) with MYC and BCL-2 and/or BCL-6 rearrangements, high-grade
B-cell lymphomas NOS), (note: other subgroups of DLBCL or LBCL from the 2016
WHO classification of lymphoid malignancies are excluded), FL (grade 1-3a;
eligibility for systemic treatment as determined by the Groupe d*Etude des
Lymphomes Folliculaires [GELF] criteria), MCL, MZL (eligible subtypes include
EMZL, MALT, NMZL and SMZL), WM, PCNSL.
- Patients in Phase 1a must meet the following:
a. For non-PCNSL indications, received at least 2 prior lines of therapy and
have no other therapies known to provide clinical benefit.
b. For PCNSL, received at least 1 prior line of therapy.
Patients in Phase 1b (Safety Expansion) must have 1 of the following
histologically documented R/R B-cell malignancies, must meet criteria for
systemic treatment, and must have received the following prior therapies based
on indication:
CLL/SLL arm:
• CLL or SLL with prior exposure to both a BTKi and BCL-2 inhibitor, unless
previously deemed ineligible for those therapies.
MCL arm:
• MCL with prior exposure to a BTKi and an anti-CD20 monoclonal antibody
(mAb)-based chemo-immunotherapy regimen.
MZL arm:
• MZL (EMZL, MALT, NMZL, SMZL) with prior exposure to an anti-CD20 mAb-based
chemo-immunotherapy regimen and an additional line of therapy.
WM arm:
• WM with prior exposure to a BTKi and an additional line of therapy.
DLBCL arm:
• DLBCL of the following subgroups with prior exposure to an anthracycline
(unless previously deemed ineligible to receive), an anti-CD20 mAb based
chemo-immunotherapy regimen, and an additional line of therapy:
o NOS, germinal center B-cell type, activated B-cell type (includes transformed
indolent lymphoma [eg, grade 3b/transformed FL] and Richter-transformed DLBCL.
o HGBL with MYC and BCL-2 and/or BCL- 6 rearrangements, and HGBL NOS
(note: other subgroups of DLBCL or LBCL from the WHO classification of lymphoid
malignancies
FL arm:
FL (grade 1-3a; eligibility for systemic treatment as determined by the GELF
criteria) with prior exposure to an anti-CD20 mAb-based chemo-immunotherapy
regimen and an additional line of therapy.
PCNSL/SCNSL arm:
• PCNSL patients who have progressed or had no response to at least 1 prior
line of therapy.
• SCNSL patients meeting criteria for non-CLL/SLL arms above with secondary CNS
involvement of lymphoma.
- Known or suspected prolymphocytic leukemia or Richter*s transformation to
Hodgkin*s lymphoma at any time preceding enrollment.
- Prior treatment for the indication under study for anti-cancer intent that
includes:
a. Radiotherapy within 2 weeks of planned start of study drug (excluding
limited plaliatiev radiation).
b. Prior systemic chemotherapy within 2 weeks of planned start of study drug.
Note: Use of intrathecal chemotherapy is allowed per institutional guidelines.
c. Prior mAb therapy within 4 weeks of planned start of study drug.
d. Prior small molecule therapy within 5 half-lives or 2 weeks (whichever is
shorter) of planned start of study drug.
e. Autologous or allogeneic stem cell transplant within 100 days prior to
planned start of study drug.
f. Chimeric antigen receptor (CAR) T-cell therapy within 100 days prior to
start of study drug (within 60 days prior to start of study drug for Phase
1b).
g. Use of systemic corticosteroids outside of dosing limits described below and
within 14 days prior to initiation of study treatment excepting those used as
prophylaxis for radio diagnostic contrast. Patients with central nervous system
lymphoma (CNSL, including both primary and secondary CNSL): no greater than 40
mg/day prednisone, or equivalent; CNSL patients using greater than 20 mg/day
prednisone, or equivalent must be clinically stable at that dose for 14 days.
All other diagnoses: no greater than 20 mg/day prednisone or equivalent.
h. Use of systemic immunosuppressive drugs other than systemic corticosteroids
for any medical condition within 60 days, prior to first dose of study drug.
i. Previously treated with a BTK degrader.
- Active, uncontrolled autoimmune hemolytic anemia or autoimmune
thrombocytopenia.
- Patient has any of the following:
a. Myocardial infarction, unstable angina, unstable symptomatic ischemic heart
disease, or placement of a coronary arterial stent within 6 months of planned
start of study drug.
b. Uncontrolled atrial fibrillation or other clinically significant
arrhythmias, conduction abnormalities, or New York Heart Association (NYHA)
class III or IV heart failure within 6 months of planned start of study drug.
c. Thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or
symptomatic cerebrovascular events), stroke, or intracranial hemorrhage within
6 months of planned start of study drug.
d. Any other significant cardiac condition (eg, pericardial effusion,
restrictive cardiomyopathy, severe untreated valvular stenosis, severe
congenital heart disease, or persistent uncontrolled hypertension defined as
systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg
despite optimal medical management) within 6 months of planned start of study
drug.
- Bleeding diathesis, or other known risk for acute blood loss.
- History of Grade >= 2 hemorrhage within 28 days of planned start of study
drug.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>This study*s phase 1a primary outcome parameters are:<br /><br>• Incidence of treatment-emergent adverse events (TEAEs); Grade 3, 4, 5 TEAEs;<br /><br>serious adverse events (SAE); TEAEs leading to study drug discontinuation;<br /><br>deaths due to TEAEs, and all deaths<br /><br>• Changes from baseline in safety parameters<br /><br>• Incidence of dose limiting toxicities (DLTs)<br /><br><br /><br>This study*s phase 1b primary outcome parameters are:<br /><br>• ORR<br /><br>• Incidence of TEAEs; Grade 3, 4, 5 TEAEs; SAEs; TEAEs leading to<br /><br>discontinuation; deaths due to TEAEs; all deaths; and changes in safety<br /><br>parameters</p><br>
- Secondary Outcome Measures
Name Time Method