A Study to Evaluate Zanubrutinib and Tislelizumab in Progressive Lymphoma Post CAR-T

NCT06167785 | Recruiting Phase 2 DMC

• 1 other identifier: OZUHN-024
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase ll study of participants with large B Cell lymphoma previously treated with anti-CD19 Chimeric antigen receptor (CAR-T) therapy. The purpose of the study is to to evaluate the efficacy of zanubrutinib and tislelizumab in patients with progressive lymphoma post anti-CD 19 CAR-T failure.

Conditions

Large B-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• determine the best overall response rate (ORR)

  To determine the best overall response rate (ORR) of the combination of zanubrutinib and tislelizumab as well as standard of care in patients previously treated with anti-CD19 CAR-T cell therapy. The best ORR is defined as the proportion of patients with a complete response (CR) or a partial response (PR) during the study, as determined by the investigator using Lugano 2014 criteria.

  2 years

Secondary Outcomes (4)

• Duration of response (DOR)

  2 years

• Progression free survival (PFS)

  2 years

• Event free survival (EFS)

  2 years

• Overall survival (OS)

  2 years

Study Arms (4)

Tislelizumab

EXPERIMENTAL

Tislelizumab 200mg intravenously every 3 weeks - initial safety run-in period

Drug: Tislelizumab

Zanubrutinib

EXPERIMENTAL

Zanubrutinib 160 mg oral twice daily - initial safety run-in period

Drug: Zanubrutinib

Tislelizumab + Zanubrutinib

EXPERIMENTAL

Tislelizumab 200mg intravenously day 1 of each cycle every 3 weeks * Zanubrutinib 160 mg oral twice daily starts day 1 of each cycle - expanded cohort

Drug: Tislelizumab + Zanubrutinib

Standard of Care

NO INTERVENTION

Patients will receive standard of care, which is up to the investigator's discretion. This may include, but not limited to, palliative chemotherapy, steroids and/or radiation as deemed appropriate.

Interventions

Tislelizumab DRUG

Tislelizumab 200mg intravenously every 3 weeks

Tislelizumab

Zanubrutinib DRUG

Zanubrutinib 160 mg oral twice daily

Zanubrutinib

Tislelizumab + Zanubrutinib DRUG

Tislelizumab 200mg intravenously day 1 of each cycle every 3 weeks + Zanubrutinib 160 mg oral twice daily starts day 1 of each cycle

Tislelizumab + Zanubrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Able and willing to provide written informed consent and to comply with the study protocol
• Radiologically measurable disease (≥ 1 nodal lesion \> 2.0 cm in the longest diameter, and/or extranodal lesion \> 1.0cm in the longest diameter)
• Relapse or refractory Large B cell Lymphoma post-CD19 directed CAR-T cell therapy within 6 weeks prior to enrollment (histological confirmation highly recommended although not mandatory)
• Intervention arm: Hemoglobin ≥ 80 g/L at screening\*
• Intervention arm: Platelet count ≥ 50 x 109/L at screening\*
• Intervention arm: Neutrophil count ≥ 1.0 x 109/L at screening\*
• Intervention arm: performance status ≤ 2 at screening
• AST and ALT \< 2.5 x upper limit of normal (ULN) at screening
• Serum total bilirubin \< 1.5 x ULN, or \< 3 x ULN in patients with documented Gilberts syndrome at screening
• Creatinine clearance ≥ 30 mL/min as estimated by Cockcroft-gault equation at screening \* Counts can be supported with growth factors or transfusions as per standard transfusion protocols

You may not qualify if:

• Life expectancy \< 30 days at the time of enrollment
• Prior exposure to bruton tyrosine kinase (BTK) or Programmed cell death (PD)-1 inhibitor at any time prior to enrollment
• Prior anaphylactic reaction to monoclonal antibody therapy at any time prior to enrollment
• On higher than physiologic doses (10mg daily) of prednisone daily at least 7 days prior to initiation of trial treatment
• Uncontrolled autoimmune disease
• Known active central nervous system (CNS) involvement disease
• History of prior allogeneic transplant or organ transplant
• Active bleeding or history of bleeding diathesis including, but not limited to,
• History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention
• History of stroke or intracranial hemorrhage within 180 days before first dose of study drug
• Difficulty with or unable to swallow oral medication, or known conditions that would significantly affect gastrointestinal function that would limit absorption of oral medication
• History of chronic or active, uncontrolled bacterial, viral or fungal infection; human T- cell lymphotropic virus type 1 seropositive status.
• Serologic status reflecting active viral hepatitis B or C infection as follows: (a) presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible if hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is undetectable (\< 20IU), and if they are willing to be on appropriate prophylaxis and undergo monitoring for HBV reactivation if clinically indicated.
• (b) Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV ribonucleaic acid (RNA) is undetectable.
• Individuals with known active human immunodeficiency (HIV) infection are eligible if CD4 and viral titres are controlled

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

University Health Network (UHN)

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

MeSH Terms

Interventions

tislelizumab; zanubrutinib

Study Officials

• John Kuruvilla, FRCPC

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John Kuruvilla, FRCPC

CONTACT

4169462821; LymphomaClinicalTrials@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2023
• First Posted: December 13, 2023
• Study Start: June 4, 2025
• Primary Completion: April 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: June 19, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)