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

Phase 1

Active, not recruiting

• Conditions: NHL; NHL, Relapsed, Adult
• Interventions: Drug: CLN-978

• Registration Number: NCT05879744
• Lead Sponsor: Cullinan Therapeutics Inc.

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-05-05
• Study First Submitted QC: 2023-05-18
• Study First Posted: 2023-05-30
• Study Start: 2023-05-31
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-30
• Last Update Posted: 2024-05-02
• Primary Completion: 2026-11
• Study Completion: 2027-04

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 90

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part A Dose Escalation	CLN-978	Patients with R/R B-NHL treated with CLN-978 in dose escalation cohorts
Part B Dose Expansion	CLN-978	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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: Cmax	24 months	Maximum concentration of CLN-978
Select PK parameters of CLN-978: AUC	24 months	Area under-the-concentration-time curve of CLN-978
Select PK parameters of CLN-978: Half-life	24 months	Half-life 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)
Assess preliminary efficacy of CLN-978 by complete response in patients with selective histologies of R/R B-NHL	24 months	Complete response (CR)
Immunogenicity of CLN-978 and potential impact on drug exposure	24 months	Incidence of anti-drug antibodies to CLN-978

Trial Locations

Locations (6)

Winship Cancer Institute at Emory University; 🇺🇸 Atlanta, Georgia, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

City of Hope; 🇺🇸 Duarte, California, United States

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States