First-in-Human (FIH) Trial of GEN3009 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas

Exclusion Criteria

• •1. Prior treatment with a CD37-targeting agent.
• •2. Prior allogeneic Hematopoietic Stem Cell Transplantation (HSCT).
• •3. Prior treatment with a CD3xCD20 bispecific antibody (Combination Expansion cohort only).
• •4. Autologous HSCT within 3 months before the first dose of GEN3009.
• •5. Lymphomas leukemic phase: high absolute lymphocyte count or the presence of abnormal cells in the peripheral blood indicating circulating lymphoma cells.
• •6. Treatment with an anti-cancer biologic including anti-CD20 therapy, radio-conjugated or toxin-conjugated antibody or chimeric antigen receptor (CAR) T-cell therapy within 4 weeks or 5 half-lives, whichever is shorter, before the first dose of GEN3009. Treatment with small molecules such as BTK inhibitors, BCL2 inhibitors, or PI3K inhibitors within 5 half-lives prior to the first dose of GEN3009.
• •7. Chemotherapy or radiation therapy within 2 weeks of the first dose of GEN3009.
• •8. Treatment with an investigational drug or an invasive investigational medical device within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of GEN3009, and at any time during the study treatment period.
• •9. Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy.
• •10. Received a cumulative dose of corticosteroids more than the equivalent of 250 mg of prednisone within the 2-week period before the first dose of GEN3009.
• •11. Has uncontrolled intercurrent illness.
• •12. Seizure disorder requiring therapy (such as steroids or anti-epileptics) (Combination Expansion cohort only).
• •13. Toxicities from previous anti-cancer therapies have not resolved to baseline levels or to Grade 1 or less except for alopecia and peripheral neuropathy.
• •14. Primary central nervous system (CNS) lymphoma or known CNS involvement at screening.
• •15. Known past or current malignancy other than inclusion diagnosis.
• •16. Had allergic reactions to anti-CD20 or anti-CD37 monoclonal antibody treatment or intolerant to GEN3009 or to the combination therapy excipients.
• •17. Has had major surgery within 4 weeks before screening or will not have fully recovered from surgery, or has major surgery planned during the time the subject is expected to participate in the trial (or within 4 weeks after the last dose of GEN3009 and/or the combination therapy).
• •18. Known history/positive serology for hepatitis B.
• •19. Known medical history or ongoing hepatitis C infection that has not been cured.
• •20. Known history of seropositivity for HIV infection.
• •21. Is a woman who is pregnant or breast-feeding, or who is planning to become pregnant while enrolled in this trial or within 12 months after the last dose of GEN3009 and/or the combination therapy.
• •22. Is a man who plans to father a child while enrolled in this trial or within 12 months after the last dose of GEN3009 and/or the combination therapy.
• •23. Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments. Additionally, vulnerable subjects or subjects under guardianship, curatorship, judicial protection or deprived of liberty), are excluded from participation in this trial.
• •24. Exposed to live/live attenuated vaccine within 4 weeks prior to initiation of GEN3009 treatment.