Lymphoma

Title: A Phase 3, Randomized, Open-Label Study of INCA033989 Versus Best Available Therapy in Participants With Essential Thrombocythemia and a CALR Mutation Previously Treated With Cytoreductive Therapy (EXCALIBUR-ET2)

MOA: IINCA033989 inhibits mutCALR induced JAK/STAT signaling and oncogenic cell proliferation.

Key Eligibility

• Confirmed diagnosis of high-risk ET
• Presence of a pathogenic CALR exon 9 mutation
  based on central lab results
• Prior treatment with at least 1 cytoreductive therapy,
  with inadequate or loss of response to the most recent
  prior ET therapy or intolerance/unacceptable toxicity
• ECOG 0-2
• Excludes presence of hematologic malignancy other
  than ET
• Prior allogenic or autologous stem-cell transplantation
  not allowed

Title: A Phase 2/3, randomized, open-label, active-comparator-controlled, parallel-group, multicenter study to evaluate the safety and efficacy of bomedemstat(MK-3543) versus best available therapy in participants with polycythemia vera who have an inadequate response to or are intolerant to hydroxyurea (MK-3543-025)

MOA: Bomedemstat (MK-3543) is an irreversible inhibitor of LSD1.

Key Eligibility:

• Subjects must have a confirmed local diagnosis of PV per WHO criteria
• Discontinued prior cytoreductive therapy for ≥5 half-lives before study
  treatment (phlebotomy permitted) and failed at least one prior cytoreductive
  therapy used to lower hematocrit
• Subjects must have a history of inadequate response, resistance to, or
  intolerant to HU per at least one of the protocol-specified criteria, based on
  modified ELN criteria for HU resistance or intolerance
• Locally assessed BM fibrosis Grade 0-1; must provide archival (≤6 months
  old) or newly obtained BM biopsy sample for central review.
• No splenomegaly or related symptoms; spleen size normal on exam or
  imaging (≤13 cm)
• Subjects currently receiving anticancer therapy are excluded
• Subjects that received bomedemstat in the past are excluded

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

A Prospective, Open-Label, Single-Arm, Phase II Study of Acalabrutinib and Rituximab in Untreated Elderly and/or Frail Patients With Diffuse Large B-Cell Lymphoma (ACRUE)

Brief Summary: The study will measure the safety, tolerability, and efficacy with acalabrutinib in combination with rituximab in treatment-naïve elderly and/or frail patients with diffuse large B-cell lymphoma (DLBCL), who are otherwise unsuitable for standard front line chemoimmunotherapy treatments.

Key Eligibility Criteria:

• ≥ 80 years of age at the time of screening, or ≥ 65 to 79 years of age at the time of screening and considered ineligible for chemoimmunotherapy
• Histologically documented DLBCL
• No prior treatment for DLBCL
• Stage II, III, or IV disease by the Ann Arbor Classification
• Eastern Cooperative Oncology Group performance status of 0, 1, or 2
• Any evidence of diseases that would make the study undesirable for the patient or that would impact compliance with the protocol excluded
• History of prior or current malignancy, that would affect compliance with the protocol or interpretation of the results excluded