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

NHL Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05879744
• Other study ID #: CLN-978-001
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: May 31, 2023
• Est. completion date: April 2027

Study information

• Verified date: April 2024
• Source: Cullinan Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 90
• Est. completion date: April 2027
• Est. primary completion date: November 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• NHL

Intervention

Drug:
• CLN-978
CD19xCD3 T cell engager

Locations

Country	Name	City	State
United States	Winship Cancer Institute at Emory University	Atlanta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	City of Hope	Duarte	California
United States	Hackensack University Medical Center	Hackensack	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Cullinan Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Define dose regimen for CLN-978	Dose-limiting Toxicities (DLTs)	24 months
Secondary	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
Secondary	Assess preliminary efficacy of CLN-978 by complete response in patients with selective histologies of R/R B-NHL	Complete response (CR)	24 months
Secondary	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
Secondary	Select PK parameters of CLN-978: AUC	Area under-the-concentration-time curve of CLN-978	24 months
Secondary	Select PK parameters of CLN-978: Cmax	Maximum concentration of CLN-978	24 months
Secondary	Select PK parameters of CLN-978: Half-life	Half-life of CLN-978	24 months
Secondary	Immunogenicity of CLN-978 and potential impact on drug exposure	Incidence of anti-drug antibodies to CLN-978	24 months