Zanubrutinib + Tafasitamab for Mantle Cell Lymphoma

(ZANU-TAFA Trial)

Recruiting at 1 trial location

Overseen By Alvaro Alencar, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Alvaro Alencar, MD

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: CNS involvement, Cardiovascular disease, HIV, others

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

Compensation: Varies

Number of Visits: 24

27 Participants Needed

Trial Summary

What is the purpose of this trial?

The main purpose of this study to find the ideal dose for the combination treatment of Zanubrutinib and Tafasitamab in patients with mantle cell lymphoma. Another purpose is to assess how well the combination treatment works in patients with the study disease.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) of at least 7 days or five half-lives for medications that are moderate or strong CYP3A inhibitors or strong CYP3A inducers, if they can be safely substituted. If you are on such medications, you may need to stop or switch them before joining the trial.

Is the combination of Zanubrutinib and Tafasitamab safe for humans?

Zanubrutinib has been studied in patients with mantle cell lymphoma and is generally well tolerated, though some patients experienced side effects like diarrhea, infections, and anemia. Tafasitamab, also known as Monjuvi, has been used in combination with other drugs for treating certain types of lymphoma, but specific safety data for its combination with Zanubrutinib is not available in the provided research. ^{1 2 3 4 5}

What makes the drug Zanubrutinib + Tafasitamab unique for treating mantle cell lymphoma?

Zanubrutinib is a next-generation Bruton tyrosine kinase inhibitor that is highly selective, which means it targets the cancer cells more precisely with fewer side effects compared to older drugs. When combined with Tafasitamab, it offers a novel approach by potentially enhancing the immune system's ability to fight the cancer, providing a new option for patients who have limited treatment choices. ^{1 2 4 5 6}

Research Team

Alvaro J. Alencar

Principal Investigator

University of Miami

Eligibility Criteria

This trial is for adults over 18 with mantle cell lymphoma confirmed by WHO criteria, who have a life expectancy of more than 4 months and normal organ/marrow function. They must have at least one measurable disease site and be willing to avoid pregnancy or fathering children during the study.

Inclusion Criteria

My lymphoma is confirmed as mantle cell type by a lab test.

My scans show active cancer areas that can be measured.

My hemoglobin level is above 9 g/dL, or above 8 g/dL if my lymphoma has spread to my bone marrow.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Early Induction

Participants receive combination therapy of Zanubrutinib and Tafasitamab during cycles 1 to 3

12 weeks

3 visits (in-person)

Late Induction

Participants continue combination therapy of Zanubrutinib and Tafasitamab during cycles 4 to 12

36 weeks

9 visits (in-person)

Extended Induction

Participants continue combination therapy of Zanubrutinib and Tafasitamab during cycles 13 to 24

48 weeks

12 visits (in-person)

Maintenance Therapy

Participants receive maintenance therapy with Zanubrutinib until progression

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 48 months

Treatment Details

Interventions

• Tafasitamab
• Zanubrutinib

Trial Overview The trial aims to determine the optimal dose of Zanubrutinib combined with Tafasitamab in treating mantle cell lymphoma. It also evaluates how effective this combination therapy is for patients with this condition.

Participant Groups

Group I: Zanu-Tafa Phase 2 Group Experimental Treatment 2 Interventions

Participants in this group will receive the combination therapy of Zanubrutinib (Zanu) at the recommended phase 2 dose (RP2D) determined during Phase 1, and Tafasitamab at standard doses, followed by maintenance therapy with Zanubrutinib until progression.. Combination therapy will be administered via induction phases as follows: 1. Early induction - cycles 1 to 3 (12 weeks) 2. Late induction - cycles 4 to 12 (36 weeks) 3. Extended induction - cycles 13-24 (48 weeks) Subsequent maintenance Zanu therapy may last up to 2 years. Total study participation is up to four (4) years.

Group II: Zanu-Tafa Phase 1 Group Experimental Treatment 2 Interventions

Participants in this group will receive combination therapy of Zanubrutinib (Zanu) and Tafasitamab (Tafa) for up to 24 cycles, followed by maintenance therapy with Zanubrutinib until progression. Each cycle is 28 days in length. Combination therapy will be administered via induction phases as follows: 1. Early induction - cycles 1 to 3 (12 weeks) 2. Late induction - cycles 4 to 12 (36 weeks) 3. Extended induction - cycles 13-24 (48 weeks) Subsequent maintenance Zanu therapy may last up to 2 years. Total study participation is up to four (4) years.

Tafasitamab is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Monjuvi for:

• Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, in adult patients who are not eligible for autologous stem cell transplant

Approved in European Union as Minjuvi for:

• Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in adult patients who are not eligible for autologous stem cell transplant

Approved in Canada as Monjuvi for:

• Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in adult patients who are not eligible for autologous stem cell transplant

Who Is Running the Clinical Trial?

Alvaro Alencar, MD

Lead Sponsor

Trials

1

Recruited

30+

BeiGene

Industry Sponsor

Trials

216

Recruited

32,500+

MorphoSys AG

Industry Sponsor

Trials

27

Recruited

6,600+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Findings from Research

Zanubrutinib, a next-generation Bruton tyrosine kinase inhibitor, shows promise as a targeted therapy for mantle cell lymphoma, particularly for patients who are elderly or have comorbidities and cannot undergo standard treatments.

An ongoing Phase III study is evaluating the safety and efficacy of zanubrutinib combined with rituximab compared to bendamustine with rituximab in patients with untreated mantle cell lymphoma who are not eligible for stem cell transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase III study of zanubrutinib plus rituximab versus bendamustine plus rituximab in transplant-ineligible, untreated mantle cell lymphoma. Dreyling, M., Tam, CS., Wang, M., et al.[2021]

In a phase 1/2 study involving 32 patients with relapsed/refractory mantle cell lymphoma, zanubrutinib showed a high overall response rate of 84%, with 25% of patients achieving a complete response and a median duration of response of 18.5 months.

Zanubrutinib was generally well tolerated, with the most common adverse events being diarrhea (43.8%) and infections (18.8% experiencing grade ≥3 infections), indicating that while there are side effects, the treatment is effective for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib for the treatment of relapsed or refractory mantle cell lymphoma. Tam, CS., Opat, S., Simpson, D., et al.[2021]

In a study of 103 patients with relapsed/refractory mantle cell lymphoma receiving CD19-directed CAR T-cell therapy (brexucabtagene autoleucel), those with a high baseline CAR-HEMATOTOX (HT) score experienced significantly worse outcomes, including prolonged neutropenia and a higher rate of severe infections.

Patients with high HT scores had a 1-year non-relapse mortality rate of 17% compared to 4.6% in those with low scores, and they also showed inferior progression-free survival and overall survival rates, highlighting the importance of the HT score in predicting treatment risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The CAR-HEMATOTOX score identifies patients at high risk for hematological toxicity, infectious complications, and poor treatment outcomes following brexucabtagene autoleucel for relapsed or refractory MCL. Rejeski, K., Wang, Y., Albanyan, O., et al.[2023]

In a phase II study involving 86 patients with relapsed mantle-cell lymphoma, zanubrutinib demonstrated a high overall response rate of 84%, with 68.6% achieving a complete response after a median follow-up of 18.4 months.

Zanubrutinib was generally well tolerated, with most adverse events being manageable; serious side effects like major bleeding were rare, indicating a favorable safety profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Patients with Relapsed or Refractory Mantle-Cell Lymphoma with Zanubrutinib, a Selective Inhibitor of Bruton's Tyrosine Kinase. Song, Y., Zhou, K., Zou, D., et al.[2021]

Zanubrutinib, a second-generation BTK inhibitor, has shown an impressive overall response rate of 84% in treating relapsed/refractory mantle cell lymphoma (MCL) based on data from 118 patients in two clinical trials, with a duration of response lasting 14-18 months.

Despite 57% of patients experiencing significant side effects, only 8% discontinued treatment, indicating that zanubrutinib is generally well tolerated and may offer advantages over first-generation BTK inhibitors like ibrutinib due to its higher selectivity and potential for combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib: a new BTK inhibitor for treatment of relapsed/refractory mantle cell lymphoma. Weaver, AN., Jimeno, A.[2020]

Zanubrutinib, an oral Bruton tyrosine kinase (BTK) inhibitor, received accelerated approval in the USA on November 14, 2019, for treating adult patients with mantle cell lymphoma (MCL) who have undergone at least one prior therapy.

The approval was based on the overall response rate (ORR) observed in phase II and I/II clinical trials, highlighting its efficacy in managing B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib: First Approval. Syed, YY.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

A Phase III study of zanubrutinib plus rituximab versus bendamustine plus rituximab in transplant-ineligible, untreated mantle cell lymphoma. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Zanubrutinib for the treatment of relapsed or refractory mantle cell lymphoma. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

The CAR-HEMATOTOX score identifies patients at high risk for hematological toxicity, infectious complications, and poor treatment outcomes following brexucabtagene autoleucel for relapsed or refractory MCL. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Treatment of Patients with Relapsed or Refractory Mantle-Cell Lymphoma with Zanubrutinib, a Selective Inhibitor of Bruton's Tyrosine Kinase. [2021]

5. Spain pubmed.ncbi.nlm.nih.gov

Zanubrutinib: a new BTK inhibitor for treatment of relapsed/refractory mantle cell lymphoma. [2020]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Zanubrutinib: First Approval. [2020]