Zanubrutinib + Tislelizumab for Lymphoma

(ZeTA Trial)

Overseen By John Kuruvilla, FRCPC

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must not be taking: BTK inhibitors, PD-1 inhibitors

Disqualifiers: Autoimmune diseases, CNS involvement, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

76 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the effectiveness of the drugs zanubrutinib and tislelizumab for individuals with large B cell lymphoma, a type of blood cancer, who did not respond to anti-CD19 CAR-T therapy. The trial will evaluate different treatment combinations to identify the most effective one. Individuals whose lymphoma has returned or not improved after anti-CD19 CAR-T therapy may qualify for this trial if they have a measurable tumor and can tolerate oral medication. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on high doses of prednisone or require treatment with warfarin or other vitamin K antagonists. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that zanubrutinib is generally safe for patients. In a large review of several studies, most patients tolerated it well, with only a few experiencing serious side effects like an irregular heartbeat. Similarly, tislelizumab has a manageable safety profile, with most side effects being mild, even with long-term use.

When used together, zanubrutinib and tislelizumab are usually well-tolerated by people with B-cell blood cancers, as studies have found. While side effects can occur, they are typically manageable. Overall, the combination appears promising, offering a good balance between effectiveness and safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Zanubrutinib and Tislelizumab for treating lymphoma because both drugs have unique mechanisms of action. Zanubrutinib is a BTK inhibitor that interferes with a protein crucial for the growth of cancer cells, offering a targeted approach that could potentially result in fewer side effects compared to traditional chemotherapy. Tislelizumab, on the other hand, is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. Unlike standard treatments like chemotherapy, steroids, or radiation, which are more generalized, this combination targets specific pathways in lymphoma cells, which might lead to improved outcomes and reduced side effects. This targeted approach is what makes these treatments stand out and generates excitement among researchers.

What evidence suggests that this trial's treatments could be effective for lymphoma?

In this trial, participants will receive either Zanubrutinib alone, Tislelizumab alone, or a combination of both. Previous studies have shown that Zanubrutinib delivers strong results in patients with cancers that have returned or are not responding to treatment, controlling the disease for two years in about 72.9% of patients. Tislelizumab also demonstrated high effectiveness, with about 87.1% of patients showing improvement. Past research combining these two treatments further improved patient outcomes, with 58.3% of patients responding well to the combination. This combination shows promise for helping patients whose lymphoma worsened after receiving anti-CD19 CAR-T therapy. ^{1 4 5 6 7}

Who Is on the Research Team?

John Kuruvilla, FRCPC

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

This trial is for adults over 18 with large B-cell lymphoma that has progressed after CAR-T therapy. Participants must have measurable disease, be able to consent and follow the study plan, and meet certain blood count criteria. Those with more than one site of disease are eligible for the intervention arm.

Inclusion Criteria

Able and willing to provide written informed consent and to comply with the study protocol

Intervention arm: Platelet count ≥ 50 x 10^9/L at screening

I have a tumor that can be measured by scans.

Exclusion Criteria

Life expectancy < 30 days at the time of enrollment

History of prior allogeneic transplant or organ transplant

I have not had major surgery in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Safety Run-in

Evaluation of the tolerability and safety of tislelizumab or zanubrutinib monotherapy

6 weeks

2 cycles of monotherapy

Expanded Cohort

Combination therapy with tislelizumab and zanubrutinib for patients with acceptable toxicity profile and no disease progression

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tislelizumab
• Zanubrutinib

Trial Overview The study tests Zanubrutinib alone or combined with Tislelizumab in patients whose lymphoma worsened post-CAR-T treatment. It's a phase II trial aiming to assess how effective these drugs are in this situation.

How Is the Trial Designed?

Group I: Zanubrutinib Experimental Treatment 1 Intervention

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

Group II: Tislelizumab + Zanubrutinib Experimental Treatment 1 Intervention

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

Group III: Tislelizumab Experimental Treatment 1 Intervention

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

Group IV: Standard of Care Active Control 1 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.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9365351/

Tislelizumab for Relapsed/Refractory Classical Hodgkin ... Tislelizumab demonstrated an overall response rate of 87.1% with a high complete response (CR) rate (62.9%) and with a median progression-free survival (PFS) of ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7041

Updated efficacy and safety results from the phase 2 study ... Conclusions: Timdarpacept in combination with tislelizumab showed promising therapeutic efficacy and a well-tolerated safety profile in cHL ...

3. asco.org asco.org/abstracts-presentations/ABSTRACT332719

Tislelizumab (BGB-A317) for relapsed/refractory (R/R) ... Tislelizumab (BGB-A317) for relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL): Long-term follow-up efficacy and safety results from a phase 2 study.

4. nature.com nature.com/articles/s41375-019-0545-2

Treatment of relapsed or refractory classical Hodgkin ... Seventy patients were enrolled in the study and received at least one dose of tislelizumab. After median follow-up of 9.8 months, 61 (87.1%) ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10440460/

Treating relapsed/refractory mature T- and NK-cell ... Tislelizumab monotherapy showed modest efficacy in R/R mature T- and NK-cell neoplasms with some long-lasting remissions. •. Tislelizumab was well tolerated and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34716199/

Tislelizumab for Relapsed/Refractory Classical Hodgkin ... Responses were durable as shown by a median duration of response of 31.3 months, and median progression-free survival (PFS) of 31.5 months. The ...

7. academic.oup.com academic.oup.com/oncolo/article/30/7/oyaf177/8169845

Long-term safety analysis of pooled data for tislelizumab as ... It demonstrates that tislelizumab has a manageable safety profile with mostly low-grade immune-mediated adverse events, even with extended treatment.