B-cell lymphomas blood cancer
Conditions
Interventions
phase1a:
Subjects in this phase who meet all inclusion criteria and do not meet any of
the exclusion criteria are assigned to 1 dose of the dose escalation period.
The subjects are given one or more
Sponsors
Nurix Therapeutics, Inc
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - 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.
Exclusion criteria
Exclusion criteria: - 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| This study*s phase 1a primary outcome parameters are: • Incidence of treatment-emergent adverse events (TEAEs); Grade 3, 4, 5 TEAEs; serious adverse events (SAE); TEAEs leading to study drug discontinuation; deaths due to TEAEs, and all deaths • Changes from baseline in safety parameters • Incidence of dose limiting toxicities (DLTs) This study*s phase 1b primary outcome parameters are: • ORR • Incidence of TEAEs; Grade 3, 4, 5 TEAEs; SAEs; TEAEs leading to discontinuation; deaths due to TEAEs; all deaths; and changes in safety parameters | — |
Secondary
| Measure | Time frame |
|---|---|
| This study*s phase 1a secondary outcome parameters are: • NX-5948 PK parameters in plasma (maximum concentration [Cmax], time at which Cmax is observed [Tmax], half-life, area under the concentration time curve up to the last measurable concentration [AUC0-last], area under the concentration time curve to the end of a dosing period [AUC0-tau], minimum concentration [Cmin], accumulation ratio). • Changes from baseline of BTK levels in B cells • Overall response rate (ORR) • Complete response (CR) rate For patients with CLL, CR/complete response with incomplete recovery (CRi) • Time to first response • Duration of response (DOR) • Progression-free survival (PFS) • Time to next therapy This study*s phase 1b secondary outcome parameters are: • NX-5948 PK parameters (Cmax, Tmax, half-life, AUC0-last, AUC0-tau, Cmin, accumulation ratio, Cerebrospinal Fluid (CSF): plasma concentration ratio) in plasma and CNS (for patients with CNS disease only) • Changes from baseline of BTK levels in B cells • CR rate For patients with CLL, CR/ complete response with incomplete recovery. • Time to first response • DOR • PFS • Time to next therapy | — |
Countries
Netherlands
Outcome results
None listed