Zanubrutinib Combined With Tislelizumab in the Treatment of r/r PMBCL and EBV+ DLBCL

A Phase II Study on the Safety and Efficacy of Zanubrutinib Combined With Tislelizumab in the Treatment of Relapsed/Refractory Primary Mediastinal Large B-cell Lymphoma and Epstein-Barr Virus-positive Diffuse Large B-cell Lymphoma

The study is to investigate the safety and efficacy of Zanubrutinib combined with Tislelizumab in the treatment of relapsed/refractory primary mediastinal large B-cell lymphoma and Epstein-Barr Virus-positive diffuse large B-cell lymphoma.

Study Overview

• Status: Recruiting
• Conditions: Primary Mediastinal Large B Cell Lymphoma; EBV-Positive DLBCL, Nos
• Intervention / Treatment: Drug: Zanubrutinib; Drug: Tislelizumab

Detailed Description

R-CHOP regimen is the first-line therapy in DLBCL which greatly improved the efficacy of diffuse large B-cell lymphoma (DLBCL) and achieved good long-term survival. However, among DLBCL patients treated with R-CHOP, EBV+ had a lower 5-year OS than EBV- patients (65% vs 82%). For primary mediastinal large B-cell lymphoma (PMBCL), although the initial treatment has a better prognosis than DLBCL, there are still 10% to 30% of PMBCL patients with primary refractory or relapsed disease, and the prognosis is poor.

Zanubrutinib combined with Tislelizumab has been proved efficient in relapsed or refractory NHLs, with ORR rate 37%, CR rate of 16.7%. This phase II, prospective, open-label, single-arm study will evaluate the efficacy and safety of Zanubrutinib combined with Tislelizumab in the treatment of relapsed/refractory primary mediastinal large B-cell lymphoma and Epstein-Barr Virus-positive diffuse large B-cell lymphoma.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: weili Zhao, PhD, MD; Phone Number: +862164370045; Email: zwl_trial@163.com
• Study Contact Backup: Name: Pengpeng Xu, PhD, MD; Phone Number: +862164370045; Email: pengpeng_xu@126.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200020
      • Recruiting
      • Ruijin Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pathologically confirmed diffuse large B-cell lymphoma, EBV positive and primary mediastinal large B-cell lymphoma
• Have received at least one prior standard therapy line including Rituximab and anthracyclines.
• Age≥18
• ECOG 0,1,2
• Imaging accessible lesions
• Life expectancy>3 months
• Informed consented

Exclusion Criteria:

• Have received systemic or local treatment including chemotherapy within three weeks before enrollment
• Chronic or active infectious diseases that require systemic antibiotics, antifungals or antiviral therapy
• Lab at enrollment (Unless caused by lymphoma) : Neutrophile<1.0*10^9/L , Hemoglobin<80g/L, Platelet<50*10^9/L, ALT or AST >2*ULN,AKP or bilirubin >1.5*ULN Creatinine>1.5*ULN
• Other uncontrollable medical condition that may that may interfere the participation of the study Not able to comply to the protocol for mental or other unknown reasons
• HIV infection
• If HbsAg positive, should check HBV DNA, DNA positive patients cannot be enrolled. If HBsAg negative but HBcAb positive (whatever HBsAb status), should check HBV DNA, DNA positive patients cannot be enrolled
• Previously received BTK inhibitor or anti-PD-1/PD-L1 treatment
• History of active autoimmune disease or severe autoimmune disease
• Need to be given corticosteroids (dose equivalent to prednisone >20 mg/day) or other immunosuppressive agents within 14 days before the study drug administration
• A history of interstitial lung disease or non-infectious pneumonia, except for those caused by radiotherapy
• Need strong cytochrome P450 (CYP) 3A inhibitor or inducer drug treatment
• Received live vaccination within 28 days before the first dose of study drug
• Patients who can receive hematopoietic stem cell transplantation, and if the subject has received allogeneic stem cell transplantation within 6 months before the first administration of the study drug or has active graft-versus-host disease requiring continuous immunosuppressive therapy
• Have received any experimental drug within 28 days, or the toxicity of any previous chemotherapy has not been relieved to ≤ Grade 1
• History of malignancy except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, unless recovered for at least 2 years
• Have a history of other active malignancies within 2 years before entering the study, excluding cervical cancer in situ, local basal cell or squamous cell skin cancer that has been cured by adequate treatment; or the previous malignant tumor is localized and has undergone local radical treatment Treatment (surgery or other forms)
• Pregnant or nursing period
• Men or women who are fertile but refuse to take appropriate contraceptive measures, unless they have been surgically sterilized

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: zanubrutinib+Tislelizumab; Zanubrutinib 160mg Bid, D1-21, po；Tislelizumab 200mg, D1, ivgtt	Drug: Zanubrutinib; 160mg Bid, D1-21, po; Drug: Tislelizumab; 200mg, D1, ivgtt

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
complete response rate	Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria	21 days after 6 cycles of treatment (each cycle is 21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events	Up to 30 days after completion of study treatment
progression free survival	Progression-free survival was defined as the time from the date of diagnosis until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria,or death from any cause, whichever occurred first.	2 year
overall survival	Overall survival was defined as the time from the date of diagnosis to the date of death from any cause. Reported is the percentage of participants with event. of disease progression or relapse, using 2014 Lugano criteria,or death from any cause, whichever occurred first.	2 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The significance of biomarkers in tissue and plasma including cfDNA, PD-1,PD-L1	Dynamic change of the expression of PD-1, PD-L1	through study completion，an average of 2 years

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Investigators: Study Chair: Weili Zhao, PhD, MD, Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): January 1, 2024

Study Registration Dates

• First Submitted: January 4, 2021
• First Submitted That Met QC Criteria: January 11, 2021
• First Posted (Actual): January 12, 2021

Study Record Updates

• Last Update Posted (Actual): March 30, 2021
• Last Update Submitted That Met QC Criteria: March 29, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: targeted therapy; EBV-Positive DLBCL, nos; Primary Mediastinal Large B Cell Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Zanubrutinib
• Other Study ID Numbers: RJ-PMBCL-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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