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