Brief Title
A Phase 1 Study of NX-5948 in Adults With Relapsed/Refractory B-cell Malignancies
Official Title
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
Brief Summary
This is a first-in-human dose escalation and cohort expansion multicenter, open-label study
designed to evaluate the safety and preliminary efficacy of NX-5948 in patients with advanced
B-cell malignancies.
Detailed Description
There are 2 parts to this study. The phase 1a portion (dose escalation) evaluates the safety
and tolerability of NX-5948 in adult patients with relapsed/refractory (R/R) chronic
lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), diffuse large B-cell lymphoma
(DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL),
or Waldenströms macroglobulinemia (WM), who have received at least 2 prior systemic therapies
(1 prior therapy for WM), and for whom no other therapies are known to provide clinical
benefit.
The phase 1b portion (cohort expansion) investigates the efficacy of NX-5948 at the dose
selected in Phase 1a in up to 5 cohorts of patients with R/R B-cell malignancies, who have
received at least 2 prior systemic therapies (or 1 prior therapy for patients with WM,
primary central nervous system lymphoma (PCNSL), or secondary central nervous system
involvement.
- Cohort A: CLL or (SLL) without a BTK C481 mutation
- Cohort B: CLL or SLL with a BTK C481 mutation
- Cohort C: DLBCL or MCL
- Cohort D: FL, MZL, or WM
- Cohort E: PCNSL, or any of the indications listed above with Central Nervous System
involvement
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Number of participants with protocol specified dose-limiting toxicities
Secondary Outcome
Pharmacokinetic (PK) profile of NX-5948: Maximum Serum Concentration
Condition
Chronic Lymphocytic Leukemia (CLL)
Intervention
NX-5948
Study Arms / Comparison Groups
Phase 1a Dose Escalation
Description: Multiple dose levels of NX-5948 to be evaluated; determination of Maximum Tolerated Dose/Phase 1b recommended dose
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
130
Start Date
November 2021
Completion Date
May 2024
Primary Completion Date
January 2024
Eligibility Criteria
Inclusion Criteria:
- Patients must be ≥18 years of age.
- Patients in Phase 1a (Dose Escalation) must have histologically confirmed R/R CLL,
SLL, DLBCL, FL, MCL, MZL, or WM.
- Patients in Phase 1a must meet the following:
o Received at least 2 prior systemic therapies (1 prior therapy for WM) and have no
other therapies known to provide clinical benefit.
- Patients in Phase 1b (Cohort Expansion) must have histologically confirmed R/R CLL,
SLL, DLBCL, FL, MCL, MZL, WM, PCNSL or any of the above indications with CNS
involvement
- Patients in Phase 1b (Cohort Expansion) must meet criteria for systemic treatment and
must have failed 2 prior lines of therapy (or 1 prior line of therapy for patients
with WM, PCNSL, or secondary CNS involvement).
- Patients must have radiographically measurable disease per response criteria specific
to the malignancy, evaluable disease in bone marrow or other compartments is also
allowed.
- ECOG performance status of 0 or 1.
- Adequate organ and bone marrow function, in the absence of growth factors and without
platelet transfusions as defined by lab parameters
Exclusion Criteria:
Key Exclusion Criteria:
- Prior treatment for the indication under study including:
1. Radiotherapy within 2 weeks of planned start of study drug (excluding limited
palliative radiation).
2. Prior chemotherapy within 4 weeks of planned start of study drug.
3. Prior monoclonal antibody therapy within 4 weeks of planned start of study drug.
4. Prior small molecule therapy within 4 weeks or 5 half-lives (whichever is
shorter) of planned start of study drug.
5. Autologous or allogeneic stem cell transplant within 100 days prior to planned
start of study drug.
6. Chimeric antigen receptor T-cell (CAR-T) therapy within 100 days prior to start
of study drug (30 days for Phase 1b). Must have evidence of B-cell recovery if
patient received prior CAR-T therapy.
7. Use of systemic corticosteroids within 14 days prior to first dose of study drug
of >20 mg/day prednisone or > 4 mg/day of dexamethasone or equivalent for
patients without CNS lymphoma (CNSL), or >40 mg/day prednisone or >8 mg/day
dexamethasone or equivalent for patients with CNSL, except for prophylaxis for
radio diagnostic contrast reactions. Patients with CNSL using >20 mg/day
prednisone or >4 mg/day dexamethasone or equivalent must be clinically stable at
that dose for 14 days.
8. Use of immunosuppressive drugs other than systemic corticosteroids within 30 days
prior to first dose of study drug
- Active, uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia.
- Patient has any of the following:
1. 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.
2. 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.
3. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, or
symptomatic cerebrovascular events), stroke, or intracranial hemorrhage within 6
months of planned start of study drug.
4. Any other significant cardiac condition (e.g., 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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Su Young Kim, MD, PhD, (415) 230-7860, [email protected]
Administrative Informations
NCT ID
NCT05131022
Organization ID
NX-5948-301
Responsible Party
Sponsor
Study Sponsor
Nurix Therapeutics, Inc.
Study Sponsor
Su Young Kim, MD, PhD, Study Director, Nurix Therapeutics, Inc.
Verification Date
November 2021