Epcoritamab in Patients With Follicular Lymphoma Not Accomplishing a CR With Upfront Chemoimmunotherapy

Inclusion Criteria:

* Biopsy-confirmed (fresh or archival tissue) follicular lymphoma grade 1-3A that is CD20+ (by immunophenotype or immunohistochemistry) at time of diagnosis. All degrees of CD20 positivity will be accepted. Composite high-grade lymphoma will be excluded.
* Subjects must have measurable disease at time of enrollment as defined by at least one lymph node with long axis ≥1.5 cm and short axis \>1.0 cm and Deauville ≥ 4 seen on baseline PET/CT
* Stage III/IV at initial diagnosis
* 1 prior line (at least 3 cycles) of systemic "upfront" or first-line therapy consisting of anti-CD20 antibody (e.g. obinutuzumab or rituximab) combined with chemotherapy (e.g. bendamustine, CHOP, CVP, or lenalidomide). Rituximab monotherapy, rituximab plus radiation, or radiation alone is not sufficient.
* Subjects need to have achieved a partial response or stable disease as best response following upfront treatment. Subjects with progressive disease will be excluded.
* Subjects must have completed all prior anti-lymphoma therapy at least 4 weeks (28 days) prior to start of epcoritamab.
* Age ≥18 years.
* 3.1.7 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 if marrow involved with disease)
  * Platelets ≥75,000 cells/mcl (transfusion allowed if marrow involved)
  * Hemoglobin ≥ 8 g/dL (transfusion allowed if marrow involved)
  * 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
  * AST(SGOT)/ALT(SGPT) ≤3× institutional ULN unless suspected/known involvement by follicular lymphoma
  * Creatinine ≤ institutional ULN OR creatinine clearance \> 45 ml/min (by Cockcroft-Gault estimate or 24-hr creatinine clearance measurement)
* Patients with hepatitis B core antibody positivity with negative PCR on antiviral therapy will be eligible but will be required to receive appropriate antiviral prophylaxis as described in Section 5.4. Patients with Hepatitis C antibody must have undetectable viral load.
* Participants with a history of prior malignancy will be eligible if all treatment of that malignancy was completed at least 2 years prior to enrollment to this study, the treatment was considered "curable-intent", and there is currently no evidence of disease.
* Resolution of toxicities from prior therapy to baseline or grade ≤1 (with the exception of grade 2 peripheral neuropathy or any grade alopecia)
* 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.

Exclusion Criteria:

* Use of investigational agents incorporated into prior induction therapy
* Uncontrolled intercurrent active infection requiring hospitalization or intravenous antimicrobial agents within 4 weeks of start of treatment
* Uncontrolled underlying cardiac conditions including but not limited to congestive heart failure grade III or IV (by NYHA) or EF \<45%, unstable angina pectoris, acute myocardial infarction \&lt; 6 months, cardiac arrhythmia
* History of uncontrolled neurologic condition including but not limited to seizure disorder, stroke, psychosis, dementia, CNS vasculitis, encephalitis
* EF \<45% or need for supplemental O2 at rest to maintain SaO2\>89%
* Immunosuppressive therapy for non-lymphoma-related indication within 28 days (or for lymphoma within 10 days) of initiation of treatment, including systemic corticosteroids 10 mg/day or greater of prednisone or equivalent
* Patients with known or suspected CNS involvement or leptomeningeal disease are excluded given concern for potentially increased risk of neurologic toxicity with epcoritamab. Patients with history of CNS malignancy from separate malignancy must have completed CNS-directed therapy and must currently have no evidence of disease
* Pregnant or breastfeeding women or participants unwilling to adhere to institutional guidelines for highly effective contraception for the duration of the therapy are excluded. This is because of the unknown but potential risk of teratogenic or abortifacient effects, as well as potential for adverse events in nursing infants secondary to treatment of the mother, as epcoritamab has not yet been studied in this patient population. A female can be determined to not be of childbearing potential if she meets any of the following criteria:

  * Premenarchal
  * Postmenopausal (\>45 years of age with amenorrhea for at least 12 months or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone \[FSH\] level \>40 IU/L or mIU/mL)
  * Permanently sterilized (e.g., bilateral tubal occlusion \[which includes tubal ligation procedures as consistent with local regulations\], hysterectomy, bilateral salpingectomy, bilateral oophorectomy)

Note: If the childbearing potential changes after start of the trial (e.g., woman who is not heterosexually active becomes active, premenarchal woman experiences menarche) a woman must begin a highly effective method of birth control, as described under 3.1.15.

* Known current alcohol or drug abuse, psychiatric illness, or unstable social situation that is likely to limit compliance with study requirements
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to epcoritamab
* Exposure to a live or a live attenuated vaccine within 4 weeks
* Patients with HIV will be excluded