Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Mantle-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Mantle Cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Zanubrutinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

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.

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.

Participants will be administered Zanubrutinib orally (PO) via capsules daily during each 28-day cycle at the following dose levels:

* Phase 1 Dose Level 1: 320 mg
* Phase 1 Dose Level -1: 240 mg
* Phase 2: Recommended dose determined in Phase 1.

Participants will be administered a 12 mg/kg dose of Tafasitamab intravenously (IV) during each 28-day cycle as follows:

* Early Induction - Cycle 1: Days 1, 4, 8, 15, and 22
* Early Induction - Cycles 2 and 3: Days 1, 8, 15 and 22
* Late Induction - Cycles 4 through 12: Days 1 and 15

Tafasitamab

Alvaro Alencar, MD

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.

Zanubrutinib and Tafasitamab in Mantle Cell Lymphoma

A Phase 1/2 Study of Zanubrutinib and Tafasitamab in Mantle Cell Lymphoma

Determination of the RP2D of Zanubrutinib, when used in combination with Tafasitamab, based on evaluation of dose limiting toxicity (DLT) in participants during the Phase 1 part of the study. DLT will be defined as the occurrence of specified adverse events (AEs) at least possibly related to the study therapy during the DLT review period.

The complete response (CR) rate among study participants in Phase 2 to Zanubrutinib at the RP2D in combination with Tafasitamab will be assessed. Response will be assessed using positron emission tomography (PET)/computerized tomography (CT) according to the Lugano 2014 criteria. CR will be defined by a Deauville score of less than or equal to (≤) 3.

The overall response rate (ORR) in study participants will be assessed. ORR will be defined at the percentage of participants achieving complete response (CR) or partial response to study therapy at at the end of early (cycles 1-3) and late induction (cycles 4-12). Response to treatment will be assessed using PET/CT according to Lugano 2014 criteria after weeks 12 and 48 of treatment. CR will be defined by a Deauville score of ≤ 3, and PR by a Deauville score of 4 or 5 with reduced uptake from baseline.

Progression-free survival among study participants will be assessed during treatment and clinical follow-up. PFS is defined as the time from start of treatment until disease progression or death.

Overall survival (OS) among study participants will be assessed during treatment and clinical follow-up. OS is defined from start of treatment until death from any cause.

The dosing, safety, and feasibility of combination of Zanubrutinib and Tafasitamab will be assessed and reported among study participants in Phase 1 as the number of participants experiencing treatment-related toxicity after start of study therapy, including treatment-related adverse events (AEs) and serious adverse events (SAEs). AEs and SAEs will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5, per physician discretion.

The duration of response (DOR) among study participants will be assessed during treatment and clinical follow-up. DOR is defined as the time from randomization to disease progression or death in patients who achieve complete response (CR) or partial response (PR).

Time to next treatment (TTNT) is defined as the time between the date of initiation of proposed treatment and the date of next subsequent systemic treatment initiation. For participants who do not have a subsequent treatment, the TTNT will be censored at last date known to be alive, except that death from any cause will be considered a competing risk event.

Spots Global Cancer Trial Database for Zanubrutinib and Tafasitamab in Mantle Cell Lymphoma

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