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

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)

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).

Study Overview

• Status: Active, not recruiting
• Conditions: NHL; NHL, Relapsed, Adult
• Intervention / Treatment: Drug: CLN-978

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute at Emory University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A Dose Escalation; Patients with R/R B-NHL treated with CLN-978 in dose escalation cohorts	Drug: CLN-978; CD19xCD3 T cell engager
Experimental: Part B Dose Expansion; 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; CD19xCD3 T cell engager

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Define dose regimen for CLN-978	Dose-limiting Toxicities (DLTs)	24 months
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

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

Collaborators and Investigators

• Sponsor: Cullinan Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: May 5, 2023
• First Submitted That Met QC Criteria: May 18, 2023
• First Posted (Actual): May 30, 2023

Study Record Updates

• Last Update Posted (Estimated): May 2, 2024
• Last Update Submitted That Met QC Criteria: April 30, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Relapsed/Refractory B-cell Non-Hodgkin Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: CLN-978-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No