Follicular Lymphoma Clinical Trials

• 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.

• Lymph node biopsy obtained in the previous 6 months

• Subjects must have measurable disease at time of enrollment as defined by at least one lymph node with long axis ≥1.5 cm

• Age ≥18 years

• ECOG performance status \> 2

• Life expectancy of \> 2 years

• Participants must meet the following organ and marrow function as defined below:

‣ Absolute neutrophil count ≥1000 cells/mcl

⁃ Platelets ≥100,000 cells/mcl

⁃ Hemoglobin ≥ 10 g/dL

• Adequate organ function, as documented by:

‣ Cardiac ejection fraction \>40% by echocardiogram or multi-gated acquisition (MUGA) scan

⁃ Total bilirubin ≤1.5 × upper limit of normal (ULN) (≤3 × ULN if attributed to lymphoma infiltration of liver)

⁃ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × ULN (≤5 × ULN if attributed to lymphoma infiltration of liver)

⁃ Alkaline phosphatase (ALP) ≤2.5 × ULN (≤5 × ULN if attributed to lymphoma infiltration of liver)

⁃ Calculated creatinine clearance by Cockcroft Gault formula ≥40 mL/min

⁃ NOTE: Irrespective of the presence of lymphoma infiltration of the liver, a participant with an AST \>3 × ULN and/or ALT \>3 × ULN concurrent with a total bilirubin \>1.5 × ULN will be excluded.

⁃ NOTE: Participants with known Gilbert syndrome will be excluded if the total bilirubin value is \>4 × ULN.

⁃ NOTE: Participants with a calculated creatinine clearance

• 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 5.2. Patients with Hepatitis C antibody must have undetectable viral load.

• Women of childbearing potential (WOCBP)\* must agree to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose of odronextamab. Egg donation is prohibited during the study and for 6 months after the last dose of the assigned study treatment. Highly effective contraceptive measures include:

‣ stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening.

⁃ intrauterine device (IUD); intrauterine hormone-releasing system (IUS)

⁃ bilateral tubal ligation/occlusion

⁃ vasectomized partner (provided that the male vasectomized partner is the sole sexual partner of the WOCBP study participant and that the vasectomized partner has obtained medical assessment of surgical success for the procedure)

⁃ sexual abstinence†, ‡.

⁃ A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to determine the occurrence of a postmenopausal state. The above definitions are according to the Clinical Trial Facilitation Group guidance. Pregnancy testing and contraception are not required for women with documented hysterectomy.

∙ WOCBP are defined as women who are fertile following menarche until becoming postmenopausal, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.

• Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the assigned study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.

⁃ Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of contraception. Female condom and male condom should not be used together.

• WOCBP must have negative serum pregnancy test at screening.

• Sexually active adult men must agree to use the following forms of medically acceptable birth control: consistent use of a condom OR vasectomy with medical assessment of surgical success, prior to initial dose, during the study and for at least 6 months following the last dose of odronextamab. Sperm donation is prohibited following odronextamab administration throughout the study and for at least 6 months following the last dose of odronextamab administration.

• Ability to understand and the willingness to sign a written informed consent document.