Study With Mosunetuzumab and Zanubrutinib in R/R Follicular Lymphoma Patients

Exclusion Criteria

• •1. Histological diagnosis different from cFL (Campo E., 2022).
• •2. R/R FL who were treated with more than three lines of previous treatment (autologous stem cell transplant performed as part of consolidation to a previous line of therapy should not be considered as a line of therapy; rituximab maintenance as part of a previous line of therapy should not be considered as a line of therapy; radiotherapy alone or in combination with rituximab is not considered a line of therapy).
• •3. Patients with stage I or II (limited stage) suitable for RT alone treatment.
• •4. Prior exposure to a Bruton's tyrosine kinase (BTK) inhibitor (BTKi).
• •5. Prior exposure to an anti-CD20xCD3 bispecific antibody (bsAbs).
• •6. Need of anticoagulation with warfarin or equivalent vitamin K antagonists (e.g. phenprocoumon). Requires ongoing treatment with a strong CYP3A inducer.
• •7. Evidence or any history of transformation from FL to other aggressive histology.
• •8. Prior allogeneic hematopoietic stem cell transplantation.
• •9. History of severe bleeding disorder (G\>3), or history of spontaneous bleeding requiring blood transfusion or other medical intervention. History of stroke or intracranial hemorrhage within 6 months before first dose of study drug
• •10. Life expectancy \< 6 months.
• •11. History of progressive multifocal leukoencephalopathy (PML).
• •12. History of hemophagocytic lymphohistiocytosis (HLH) or chronic active EBV.
• •13. History of autoimmune disease, including, but not limited to: myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
• •14. Primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening as confirmed by mandatory brain computed tomography (CT) scan and, if clinically indicated, by lumbar puncture.
• •15. Subject has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, investigational therapy, including targeted small molecule agents within 14 days prior to the first dose of study drug. If receiving glucocorticoid treatment at screening, must be a maximum daily dose of prednisone 10 mg (or equivalent).
• •16. Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 90 days prior to first therapy administration.
• •17. Any uncontrolled or significant cardiovascular disease \[NYHA class ≥2\].
• •1. Myocardial infarction within 6 months before screening
• •2. Unstable angina within 3 months before screening
• •3. New York Heart Association class III or IV congestive heart failure
• •4. History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes)
• •18. Significant history of neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent.
• •19. Any history of other active malignancies within 3 years prior to study entry, except for adequately treated in situ carcinoma of the uterine cervix, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, non-muscle-invasive bladder cancer, localized Gleason score 6 prostate cancer, previous malignancy confined and surgically resected with curative intent.
• •20. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
• •1. Uncontrolled and/or active systemic infection (viral, bacterial or fungal), including active ongoing infection from SARS-CoV-2;
• •2. Chronic or acute hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen (Ag) negative, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from previous infection or intravenous immunoglobulins (IVIG) may participate; inactive carriers (HBsAg positive with undetectable HBV- DNA) are eligible. Patients with presence of HCV antibody are eligible only if PCR negative for HCV-RNA;
• •21. HIV seropositivity.
• •22. Pregnant or lactating women. If female, the patient is pregnant or breast-feeding.
• •23. Severe or debilitating pulmonary disease.
• •24. Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
• •25. Underlying medical conditions that, in the investigator's opinion, will render the administration of study drug hazardous or obscure the interpretation of toxicity or AEs.
• •26. Major surgery within 4 weeks of the first dose of study drug.
• •27. Vaccination or requirement for vaccination with a live vaccine within 28 days prior to the first dose of study drug or at any time during planned study treatment.
• •28. Ongoing alcohol or drug addiction or any psychiatric condition(s) which would compromise ability to comply with study procedures.
• •29. Hypersensitivity to zanubrutinib or mosunetuzumab or any of the other ingredients of the applicable study drugs.
• •30. Active and/or ongoing autoimmune anemia and/or autoimmune thrombocytopenia (eg, idiopathic thrombocytopenia purpura).