Blood

A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study Of Mavorixafor In Participants With Congenital And Acquired Primary Autoimmune And Idiopathic Chronic Neutropenic Disorders Who Are Experiencing Recurrent And/Or Serious Infections

MOA: Mavorixafor is a CXCR4 antagonist that blocks the binding of the CXCR4 ligand, SDF 1α/CXC chemokine ligand 12.

Key Eligibility:

• Diagnosis of congenital or acquired primary autoimmune and
  idiopathic chronic neutropenic disorder
• Subjects must be receiving G-CSF or other active background
  therapy for the past 12 months with ongoing infections, be on a
  stable dose and schedule for at least 4 weeks before screening,
  and maintain this regimen throughout the study
• Subjects with a diagnosis of secondary neutropenia are excluded
• Subjects with any of the following diagnoses are excluded:
  • Aplastic anemia
  • WHIM syndrome
  • Certain CNs
  • Neutropenia associated with a Duffy-null phenotype

A Phase II, Nonrandomized, Single-Arm Study of Elranatamab Outpatient Administration in Patients with Relapsed/Refractory Multiple Myeloma

MOA; Elranatamab is a bispecific antibody targeting BCMA and CD3, designed to redirect T cells to eliminate malignant plasma cells in MM.

Key Eligibility:

• Documented diagnosis of relapsed/refractory MM according to IMWG criteria
  • Must have received ≥1 prior LOT that includes both
    lenalidomide and an anti-CD38 mAb(in the same or
    separate prior lines)
• Must have measurable disease at screening
• Subjects must be able and willing to receive prophylaxis for VZV and PJP
• Subjects with the following plasma cell disorders are excluded:
  active plasma cell leukemia, Waldenström’s macroglobulinemia,
  POEMS syndrome, or primary AL amyloidosis
• Subjects with active CNS multiple myeloma involvement are
  excluded

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Elritercept (KER 050) for the Treatment of Transfusion-Dependent Anemia in Adult Participants with Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) (RENEW)

MOA: Elritercept is a recombinant fusion protein designed to inhibit signaling by select TGF-β superfamily ligands, including activin A, activin B, GDF8, and GDF11.

Key Eligibility

• Diagnosis of MDS with or without RS according to WHO 2016 classification that
  meets the IPSS-R classification of very low-, low-, or intermediate-risk MDS
• Transfusion dependent (16 weeks pre-randomization)
  a) LTB: 4–7 RBC units / 16 weeks
  b) HTB: ≥ 8 RBC units / 16 weeks
  • Pre-treatment Hgb levels <10 g/dL
  • At least 2 transfusion events and 1 in each of the 2 consecutive 8 weeks
    blocks over 16 weeks
• Subjects must be refractory (≥4 weeks of treatment), intolerant (any duration of
  treatment), or unlikely to respond to ESA treatment (EPO > 200 U/L)
• Subjects must have less than 5% blasts in an evaluable bone marrow aspirate
  collected at screening
• Subjects with del(5q) MDS, therapy-related (secondary) MDS, or any known
  history of AML are excluded
• Subjects with anemia due to any other known cause are excluded

NX-5948-201: A Single-arm, Phase 2, Open-label, Multicenter Study to Evaluate NX-5948 in Adults with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Previously Exposed to a Bruton's Tyrosine Kinase Inhibitor (BTKi) and a B-cell Lymphoma-2 Inhibitor (BCL-2i)

MOA: NX-5948 (bexobrutideg) is a CTM that induces the degradation of BTK in cells through recruitment of CRBN and promotes the formation of a ternary complex of CRBN, NX-5948, and BTK.

Key Eligibility Criteria:

• Confirmed diagnosis of relapsed/refractory CLL/SLL
• ECOG ≤2
• Subjects must have prior exposure to a cBTKi, ncBTKi, and BCL-2i either in separate LOT or in combination
• Subjects must have measurable disease by CT
• Subjects previously treated with a BTK degrader are excluded
• Subjects with a known or suspected prolymphocytic
  leukemia or Richter’s transformation are excluded

Outpatient Administration of Teclistamab or Talquetamab for Multiple Myeloma (OPTec/OPTal)

MOA: Teclistamab targets the CD3 receptor complex on T cells and BCMA on B-lineage cells. Talquetamab targets the D3 receptor complex in T cells and GPRC5D expressing cells.

Key Eligibility Criteria:

• Must have documented diagnosis of MM according to the IMWG diagnostic criteria
• Must have received 2 or more prior MM therapies including a PI, IMiD and CD38 antibody
• Patients with a high tumor burden, defined as having ≥60% plasma cell infiltrate on the bone marrow biopsy or aspirate, whichever is higher, or with multiple extramedullary disease sites or plasmacytomas are excluded
• Patients with a rapidly progressing disease per investigator assessment are excluded

A Phase 2 study to evaluate the efficacy and safety of selinexor monotherapy in subjects with JAK inhibitor (JAKi)-naïve myelofibrosis and moderate thrombocytopenia

Brief Summary: The main purpose of this study with corresponding optional expansion is to evaluate the efficacy of selinexor in JAKi-naïve participants with myelofibrosis (MF) and moderate thrombocytopenia based on spleen volume reduction (SVR). Additional efficacy and safety parameters will also be assessed during the study.

Key Eligibility Criteria:

• A diagnosis of MF or post-ET or post-PV MF
• Measurable splenomegaly during the screening period 
• ECOG Performance Status less than or equal to (<=) 2
• More than 10% blasts in peripheral blood or bone marrow (accelerated or blast phase) excluded
• Previous treatment with JAK inhibitors for MF excluded
• Previous treatment with selinexor or other XPO1 inhibitors excluded

A Phase 1/3 Study to Evaluate Efficacy and Safety of Selinexor, a Selective Inhibitor of Nuclear Export, in Combination With Ruxolitinib in Treatment-naïve Patients With Myelofibrosis

Brief Summary: This is a global, multicenter, 2-part study to evaluate the efficacy and safety of selinexor plus ruxolitinib in JAK inhibitor (JAKi) treatment-naïve myelofibrosis (MF) participants.

Key Eligibility Criteria:

• A diagnosis of primary MF or post-essential thrombocythemia (ET) or postpolycythemia- vera (PV) MF
• Active symptoms of MF as determined by presence of at least 2 symptoms using the Myelofibrosis Symptom Assessment Form (MFSAF) V4.0.
• Participants with international prognostic scoring system (DIPSS) risk category of intermediate-1, or intermediate-2, or high-risk.
• Measurable splenomegaly during the screening period as demonstrated by spleen volume of greater than or equal to (>=) 450 cubic centimeter (cm^3) .
• Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to (<=) 2.
• More than 10% blasts in peripheral blood or bone marrow (accelerated or blast phase) excluded.
• Previous treatment with JAK inhibitors for MF excluded.
• Previous treatment with selinexor or other XPO1 inhibitors excluded.

A Phase 1b, Open-Label Study to Assess the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Povetacicept in Subjects with Autoimmune Cytopenias (RUBY-4)

Brief Summary: The goal of this clinical study is to evaluate povetacicept in adults with autoimmune cytopenias of immune thrombocytopenia, autoimmune hemolytic anemia, and cold agglutinin disease to determine if povetacicept is safe and potentially beneficial in treating these diseases. 

Key Eligibility Criteria:

• Immune Thrombocytopenia (ITP):
  • Documented persistent or chronic primary ITP of at least 12 weeks duration from diagnosis to Cycle 1 Day 1
  • History of failure or relapse to at least 2 treatment regimens for ITP
• Warm Autoimmune Hemolytic Anemia (wAIHA):
  • Diagnosis of primary wAIHA of at least 12 weeks duration documented with a current or prior positive direct antiglobulin test (DAT) for anti-IgG (±C3d)
  • Documented history of anemia with hemoglobin ≤10 g/dL
• Cold Agglutinin Disease (CAD):
  • Diagnosis of primary CAD of at least 12 weeks duration 
  • Documented history of anemia with hemoglobin ≤10 g/dL
• Secondary AIHA, CAD, or ITP excluded