GPL in Patients with Relapsed/refractory Diffuse Large B Cell Lymphoma

Exclusion Criteria

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• •1. Has previously received 4 or more lines of anticancer chemotherapies (autologous hematopoietic stem cell transplantation is considered as 1 line of treatment).
• •2. Has current evidence or history of macrophage activation syndrome/hemophagocytic lymphohistiocytosis (MAS/HLH).
• •3. Prior treatment with glofitamab.
• •4. Has acute bacterial, viral, or fungal infections confirmed with positive blood culture or diagnosed clinically in case there is no positive blood culture.
• •5. Has known active infection or reactivation of latent infection, regardless of bacteria, viruses, fungi, mycobacteria, or other pathogens, or has an episode of major infection requiring hospitalization or intravenous antibiotic treatment within 4 weeks from the dose of study drug.
• •6. Has received systemic immunotherapy including a radioimmunoconjugate, an antibody-drug conjugate, or an immune checkpoint inhibitor (eg. anti-cytotoxic T-lymphocyte-associated protein 4 \[anti-CTLA4\], anti-programmed death 1 \[anti-PD1\], and anti-programmed death ligand 1 \[anti-PDL1\]) within 4 weeks from the dose of study drug or within 5 half-lives of the drug.
• •7. Has experienced treatment-emergent immune-related AE during previous immunotherapy.
• •8. Has received radiotherapy, anticancer chemotherapy, or other experimental chemotherapy including chimeric antigen receptor therapy (CAR-T) within 4 weeks from the first dose of study drug.
• •9. Has received a homologous hematopoietic stem cell transplantation within 1 year or has previously received a solid organ transplantation.
• •10. Has received autologous hematopoietic stem cell transplantation within 100 days from the first dose of study drug.
• •11. Has a graft-versus-host disease (GVHD) requiring treatment.
• •12. Is not able to have oral intake of study drug.
• •13. Has resistance to BTK inhibitors or lenalidomide (defined as PFS less than 6 months after BTK inhibitors or lenalidomide).
• •14. Has previously been diagnosed with a malignancy other than the cancer included in this study, except appropriately treated basal cell carcinoma, squamous cell skin cancer, in situ cancer, and at least 5 years of disease free status from previous cancer.
• •15. Has a clinically significant cardiovascular disease as follows: a heart disease of New York Heart Association Functional Class III or IV or Objective class C or D, or had myocardial infarction within 6 months, or has uncontrolled arrhythmia or unstable angina. Of note, patients with well-controlled and asymptomatic atrial fibrillation are eligible.
• •16. Malabsorption syndrome, diseases that seriously affect gastrointestinal function, resection of the stomach or small intestine that may affect absorption, inflammatory bowel disease with symptoms, partial or complete intestinal obstruction, or obesity surgery such as gastric restriction and gastric bypass surgery.
• •17. Has a history of drug-specific hypersensitivity or anaphylaxis to the study drug (including active ingredients or excipients).
• •18. A condition with uncontrolled active bleeding or potential bleeding (e.g., hemophilia or von Willebrand disease)
• •19. Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP).
• •20. Requiring treatment with a strong cytochrome P450 (CYP)3A4 inhibitor/inducer.
• •21. Is receiving or needs to receive warfarin or a corresponding vitamin K antagonist (e.g., phenprocoumon within 7 days from the first dose of study drug.
• •22. Prothrombin time (PT)/international normalized ratio (INR) or activated partial thromboplastin time) (aPTT) (in the absence of lupus anticoagulant) \>2x ULN
• •23. Needs to receive a proton pump inhibitor (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole).Patients receiving proton pump inhibitors will be eligible after changing regiment to H2-receptor antagonists or antacids.
• •24. History of cerebrovascular disease or event including stroke or intracranial hemorrhage within 6 months prior to the first dose of study drug.
• •25. Has underwent major surgery within 28 days of the first dose of study drug. Subjects who underwent major surgery should be properly recovered prior to the first dose of the drug.
• •26. Serological status of hepatitis B or hepatitis C: If HBsAg is positive, the subject may be enrolled if he/she is on appropriate antiviral treatment and HBV DNA is not detectable. Patients who are HBcAb-positive, HBsAg-negative, and HBV DNA-negative should receive appropriate antiviral preventive treatment during the study. Patients who are positive for hepatitis C antibodies should have negative PCR results, and those with positive PCR results will be excluded. However, the salvage cohort group does not require preventive treatment. For safety, patients will continue active anti-HBV treatment with HBV DNA tests performed every 3 months until at least 6 months after completion of hie/her study participation. HBV DNA will be tested by PCR.
• •27. Has an active tuberculosis (a history of exposure or a history of positive tuberculosis testing with clinical symptoms or physical or radiological findings) or a latent tuberculosis requiring treatment.
• •28. Has a primary or secondary CNS lymphoma at enrollment.