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

Study Overview
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Brief Summary
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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).

Official Title
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A Phase 1, Open-label, Dose Escalation and Dose Expansion Study of CLN-978 in Patients With Relapsed/Refractory (R/R) B-cell Non-Hodgkin Lymphoma (B-NHL)

Conditions
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NHL, NHL, Relapsed, Adult

Intervention / Treatment
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* Drug: CLN-978


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A Dose Escalation<br>Patients with R/R B-NHL treated with CLN-978 in dose escalation cohorts | Drug: CLN-978<br>* CD19xCD3 T cell engager<br>|
| Experimental: Part B Dose Expansion<br>Patients with R/R DLBCL, R/R FL and other R/R B-NHL treated with CLN-978 at a dose selected from the Part A Dose Escalation arm. | Drug: CLN-978<br>* CD19xCD3 T cell engager<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of CLN-978 based on AEs, AESIs, and SAEs | Incidence and severity of adverse events (AEs)/adverse events of special interest (AESIs)/serious adverse events (SAEs); incidence of dose interruptions and delays | 24 months | 
| Define dose regimen for CLN-978 | Dose-limiting Toxicities (DLTs) | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess preliminary efficacy of CLN-978 by overall response in patients with selective histologies of R/R B-NHL | Overall response rate (ORR) | 24 months | 
| Assess preliminary efficacy of CLN-978 by complete response in patients with selective histologies of R/R B-NHL | Complete response (CR) | 24 months | 
| Assess preliminary efficacy of CLN-978 by duration of response in patients with selective histologies of R/R B-NHL | Duration of response (DOR) | 24 months | 
| Select PK parameters of CLN-978: AUC | Area under-the-concentration-time curve of CLN-978 | 24 months | 
| Select PK parameters of CLN-978: Cmax | Maximum concentration of CLN-978 | 24 months | 
| Select PK parameters of CLN-978: Half-life | Half-life of CLN-978 | 24 months | 
| Immunogenicity of CLN-978 and potential impact on drug exposure | Incidence of anti-drug antibodies to CLN-978 | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsed/Refractory B-cell Non-Hodgkin Lymphoma