A Study of CLN-978 in Patients With Relapsed or Refractory (R/R) B Cell Non-Hodgkin Lymphoma (B-NHL)

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) PS ≤ 2
• Documented diagnosis of one of the below CD19+ B-cell neoplasms according to WHO classification (Swerdlow et al., 2016) or WHO classification 2008:

• Diffuse large B-cell lymphoma - de novo or transformed
• High-grade B-cell lymphoma
• Primary mediastinal large B-cell lymphoma
• Follicular lymphoma
• Mantle cell lymphoma
• Marginal zone lymphoma (nodal, extranodal, or mucosa-associated)
• Relapsed, progressive, and/or refractory disease after at least 2 lines of therapy.
• For Part B expansion cohorts:

• Cohort B1: R/R DLBCL that has relapsed after at least 2 prior therapies including a CD20 monoclonal antibody and anthracycline.
• Cohort B2: R/R FL (grade 1-3a) that has relapsed after at least 2 prior therapies including CD20 monoclonal antibody and an alkylating agent.
• Cohort B3: Other R/R B-NHL.
• Measurable disease defined as ≥1 measurable nodal lesion (long axis >1.5 cm and short axis >1.0 cm) or ≥1 measurable extra-nodal lesion (long axis >1.0 cm) on computed tomography (CT) scan or magnetic resonance imaging (MRI) AND baseline fluorodeoxyglucose-positron emission tomography (FDG-PET) scan demonstrating positive lesion(s) compatible with CT- or MRI-defined anatomical tumor sites.
• Laboratory parameters including the following:

• Lymphocyte count < 5 x 10^9/L
• Platelet count ≥ 75 x 10^9/L
• Absolute neutrophil count ≥ 1.0 x 10^9/L; growth factor support allowed in cases of documented bone marrow involvement
• Hemoglobin ≥ 9 g/dL, with or without transfusion
• Creatinine clearance ≥ 45 mL/min
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN), except patients with confirmed Gilbert's Syndrome
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN (unless attributed to hepatic involvement by lymphoma)

Exclusion criteria

• Primary CNS lymphoma or known CNS involvement by lymphoma at study screening
• Known past or current malignancy other than the inclusion diagnosis
• Known clinically significant cardiac disease
• Significant central nervous system disease
• Prior organ allograft
• Confirmed history or current autoimmune disorder or other disease requiring ongoing immune suppression
• Active Hepatitis C Virus (HCV), Hepatitis B Virus (HBV), or known Human Immunodeficiency Virus (HIV) infection
• Live virus vaccines within 28 days of the first dose of CLN-978, during treatment, and until the end of last dose of CLN-978
• Known active, clinically significant bacterial, viral, fungal, mycobacterial, parasitic, or other infection, including coronavirus disease of 2019 (COVID-19) infection, at the time of enrollment or within 7 days of the first dose of CLN-978.
• Prior treatment with any of the following:

• Allogeneic HSCT
• Autologous HSCT within 30 days prior to the first dose of CLN-978
• Chimeric antigen receptor T cell therapy (CAR-T) within 30 days prior to the first dose of CLN-978
• Any investigational CD19 x CD3 T cell engager (TCE)
• Unconjugated CD19 monoclonal antibody ≤ 4 weeks prior to the first dose CLN-978
• Radio-conjugated or CD19 antibody-drug conjugate ≤ 12 weeks prior to the first dose CLN-978
• Investigational or standard of care monoclonal antibodies, chemotherapy, or other investigational agent ≤ 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of CLN-978
• Radiation therapy (XRT), with the exception of focal treatment for symptom control, ≤ 4 weeks of the first dose of CLN-978
• Woman of child-bearing potential who is pregnant, breast-feeding, or plans to become pregnant
• Male patients who plan to father a child or donate sperm within 120 days of last study drug administration