IBI376 in Patients With Relapsed or Refractory Follicular Lymphoma/Marginal Zone Lymphoma

Patients will be recruited for 2 cohorts. Cohort A will recruit 58 RRFL subjects, and Cohort B will recruit 62 RRMZL subjects.

Inclusion criteria

• Aged 18 years or older.
• Histologically confirmed, relapsed or refractory, follicular B-cell non-Hodgkin lymphoma (NHL) (FL) Grade 1, 2, and 3a or MZL.
• Ineligible for hematopoietic stem cell transplant.
• Definition of RRFL or RRMZL: Subjects should have received 2 or more prior therapies for FL/MZL included at least one regimen containing Rituximab. Subjects should be refractory to Rituximab or experienced disease progression after achieved remission or disease progression within 6 months since last therapy.
• Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ≥ 1 lesion that measures > 1.5 cm in the longest dimension and ≥ 1.0 cm in the longest perpendicular dimension as assessed by computed tomography (CT) or magnetic resonance imaging (MRI).
• Subjects must be willing to undergo an incisional, excisional, or core needle lymph node or tissue biopsy or provide a lymph node or tissue biopsy from the most recent available archival tissue.
• ECOG performance status 0 to 2.
• Life expectancy ≥ 12 weeks.
• Adequate hematologic, hepatic, and renal function.
• Willingness to avoid pregnancy or fathering children.

Exclusion criteria

1 . Known histological transformation from indolent NHL to diffuse large B-cell lymphoma.

• History of central nervous system lymphoma (either primary or metastatic).

• Prior treatment with idelalisib, other selective PI3Kδ inhibitors, or a pan-PI3K inhibitor.

• Prior treatment with a Bruton's tyrosine kinase inhibitor (eg, ibrutinib).

• Allogeneic stem cell transplant within the last 6 months, or autologous stem cell transplant within the last 3 months before the date of study treatment administration.

• Active graft-versus-host disease. 7. Subjects positive for hepatitis B surface antigen or hepatitis B core antibody will be eligible if they are negative for HBV-DNA. Subjects positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA.