NHL, NHL, Relapsed, Adult
Conditions
Keywords
Relapsed/Refractory B-cell Non-Hodgkin Lymphoma
Brief 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).
Interventions
DRUGCLN-978
CD19xCD3 T cell engager
Sponsors
Cullinan Therapeutics Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of CLN-978 based on AEs, AESIs, and SAEs | 24 months | Incidence and severity of adverse events (AEs)/adverse events of special interest (AESIs)/serious adverse events (SAEs); incidence of dose interruptions and delays |
| Define dose regimen for CLN-978 | 24 months | Dose-limiting Toxicities (DLTs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess preliminary efficacy of CLN-978 by duration of response in patients with selective histologies of R/R B-NHL | 24 months | Duration of response (DOR) |
| Select PK parameters of CLN-978: AUC | 24 months | Area under-the-concentration-time curve of CLN-978 |
| Assess preliminary efficacy of CLN-978 by overall response in patients with selective histologies of R/R B-NHL | 24 months | Overall response rate (ORR) |
| Select PK parameters of CLN-978: Half-life | 24 months | Half-life of CLN-978 |
| Immunogenicity of CLN-978 and potential impact on drug exposure | 24 months | Incidence of anti-drug antibodies to CLN-978 |
| Select PK parameters of CLN-978: Cmax | 24 months | Maximum concentration of CLN-978 |
| Assess preliminary efficacy of CLN-978 by complete response in patients with selective histologies of R/R B-NHL | 24 months | Complete response (CR) |
Countries
United States
Outcome results
None listed