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

• Status: Not yet recruiting
• Trial end date: 2027-04-01
• Target enrollment: 0
• Participant gender: All

Summary

CLN-978-001 is a Phase 1, open-label, dose escalation and dose expansion study of CLN-978 in patients with Relapse/Refractory (R/R) B-cell Non-Hodgkin Lymphoma (B-NHL).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cullinan Oncology, LLC

Criteria

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:

1. Diffuse large B-cell lymphoma - de novo or transformed

2. High-grade B-cell lymphoma

3. Primary mediastinal large B-cell lymphoma

4. Follicular lymphoma

5. Mantle cell lymphoma

6. 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:

1. Cohort B1: R/R DLBCL that has relapsed after at least 2 prior therapies including a CD20 monoclonal antibody and anthracycline.

2. 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.

3. 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:

1. Lymphocyte count < 5 x 10^9/L

2. Platelet count ≥ 75 x 10^9/L

3. Absolute neutrophil count ≥ 1.0 x 10^9/L; growth factor support allowed in cases of documented bone marrow involvement

4. Hemoglobin ≥ 9 g/dL, with or without transfusion

5. Creatinine clearance ≥ 45 mL/min

6. Total bilirubin ≤ 1.5 × upper limit of normal (ULN), except patients with confirmed Gilbert's Syndrome

7. 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:

1. Allogeneic HSCT

2. Autologous HSCT within 30 days prior to the first dose of CLN-978

3. Chimeric antigen receptor T cell therapy (CAR-T) within 30 days prior to the first dose of CLN-978

4. Any investigational CD19 x CD3 T cell engager (TCE)

5. Unconjugated CD19 monoclonal antibody ≤ 4 weeks prior to the first dose CLN-978

6. Radio-conjugated or CD19 antibody-drug conjugate ≤ 12 weeks prior to the first dose CLN-978

7. 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

8. 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