Epcoritamab in Previously Treated WM

Inclusion Criteria

• •A diagnosis of lymphoplasmacytic lymphoma/WM that is CD20+ by immunophenotype or immunohistochemistry confirmed by bone marrow biopsy/aspirate (fresh or archival tissue acceptable) at time of most recent progression. All degrees of CD20 positivity will be accepted.
• •Serum IgM level \>2x upper limit of normal (ULN)
• •Meeting criteria for initiation of treatment per IWWM2 criteria \[Kyle Semin Oncol 2002\], including but not limited to hyperviscosity syndrome, peripheral neuropathy, cold agglutinin disease, cryoglobulinemia, amyloidosis, cytopenias due to bone marrow infiltration, symptomatic or bulky lymph nodes, symptomatic splenomegaly, constitutional symptoms not otherwise explained by other causes, signs of organ dysfunction secondary to WM
• •At least one prior line of treatment that was discontinued either due to intolerance or disease progression
• •Prior therapies must have included an anti-CD20 antibody (e.g. rituximab) and a BTK inhibitor (e.g. ibrutinib, zanubrutinib). Patients who received ibrutinib and rituximab in combination as first line therapy will be eligible. BTKi should be stopped to allow a washout period of no less than 4 half-lives prior to epcoritamab.
• •Age ≥18 years
• •ECOG performance status £ 2
• •Life expectancy of greater than 2 years
• •Participants must meet the following organ and marrow function as defined below:
• •* absolute neutrophil count ≥1000 cells/mcl (G-CSF allowed)
• •* absolute lymphocyte count ≥200 cells/mcl
• •* platelets ≥75,000 cells/mcl OR ≥50,000 cells/mcl in the presence of bone marrow involvement or splenomegaly (Note: no PLT transfusions within 7 days prior to screening)
• •* hemoglobin ≥ 8 g/dL (transfusion allowed)
• •* total bilirubin ≤ 1.5 institutional upper limit of normal (ULN). In patients with suspected/known Gilbert's disease total bilirubin up to 3x ULN will be allowed but direct bilirubin must be ≤ 2 x ULN
• •* AST(SGOT)/ALT(SGPT) ≤3× institutional ULN
• •* creatinine ≤ institutional ULN OR
• •* creatinine clearance \>45 ml/min (by Cockcroft-Gault estimate or 24-hr creatinine clearance measurement)
• •Subject does not have an active (PCR-positive) Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection. If laboratory evidence for a chronic infection with hepatitis B, close monitoring and prophylactic therapy is required as described in Section 5.4.
• •Ability to understand and the willingness to sign a written informed consent document.
• •Females of childbearing potential must agree to practice a highly effective method of birth control (as defined by the EU Clinical Trial Facilitation Group) consistent with local regulations regarding the use of birth control methods for patients participating in clinical trials:
• •* Established use of oral, injected or implanted combined (estradiol and progesterone containing) hormonal contraception;
• •* Placement of an intrauterine device (IUD) or intrauterine system (IUS);
• •* Male partner sterilization (the vasectomized partner should be the sole partner for that patient)
• •* True abstinence (when this is in line with the preferred and usual lifestyle of the patient)
• •Women must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the trial and for 12 months after receiving the last dose of epcoritamab. Men must also not donate sperm during the trial and for 12 months after receiving the last dose of epcoritamab.
• •A man who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control (i.e. use of condom) during the trial and for 12 months after receiving the last dose of epcoritamab.
• •Patients with HIV may be enrolled if they are on stable antiretroviral therapy, have an undetectable viral load, and CD4 count \> 250 cells/mm3.