What side effects are associated with this type of intervention?

Common treatments for lymphoma, particularly those involving BTK inhibitors like Nemtabrutinib, often include side effects such as infections, bleeding, and cardiovascular issues like hypertension and atrial fibrillation. Other non-hematologic adverse effects can include fatigue, gastrointestinal disturbances, and dermatologic reactions. These treatments aim to manage relapsed or refractory hematologic malignancies but require careful monitoring due to their potential toxicities.

What prior FDA approvals exist?

The FDA has approved several BTK inhibitors for the treatment of lymphoma. Ibrutinib (Imbruvica) was the first BTK inhibitor approved and is used for various types of B-cell malignancies, including mantle cell lymphoma, chronic lymphocytic leukemia (CLL), and Waldenström's macroglobulinemia. Acalabrutinib (Calquence) is another BTK inhibitor approved for mantle cell lymphoma and CLL. Zanubrutinib (Brukinsa) has also been approved for mantle cell lymphoma. These drugs work by inhibiting Bruton's tyrosine kinase, thereby disrupting B-cell receptor signaling and inducing apoptosis in malignant B cells.

What other types of research exist?

Promising novel alternatives to Nemtabrutinib for lymphoma patients include pembrolizumab, TTI-621, BNZ-1, and MRG-106. These treatments are still in trials and have not yet demonstrated long-term remissions, but they represent emerging options in the field.

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BTK Inhibitor

Nemtabrutinib for Blood Cancers

Phase 1 & 2

Waitlist Available

Research Sponsored by ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

Ability to swallow oral medications without difficulty

Must not have

Participants currently being treated with specific drugs as detailed in the provided text

Active Hepatitis B or Hepatitis C infection

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 86 months

Awards & highlights

Summary

This trial is testing a new pill called nemtabrutinib for patients with blood cancers that have returned or didn't respond to other treatments. The goal is to find a safe and effective dose of the drug. Nemtabrutinib is a new drug being tested for blood cancers, designed to reduce adverse effects.

Who is the study for?

This trial is for adults with certain blood cancers like lymphoma and leukemia that have come back or didn't respond to treatment. They must have tried at least two other treatments, be able to take pills, and not be eligible for standard therapies. Pregnant women, those with serious health issues, recent heart attacks, active infections or a history of cancer within the last year (with some exceptions) can't join.

What is being tested?

The study tests Nemtabrutinib tablets in patients with relapsed or refractory hematologic malignancies. It looks at how safe and tolerable the drug is, as well as its effects on the body and how it's processed by measuring various parameters over time without comparing it to another treatment.

What are the potential side effects?

While specific side effects are not listed here, common ones may include nausea, fatigue, diarrhea; rare but more severe could involve liver problems or allergic reactions. The trial will closely monitor participants for any adverse reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can take care of myself and am up and about more than half of the day.

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I can take pills without any trouble.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am currently taking specific medications as listed.

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I do not have an active Hepatitis B or C infection.

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My cancer has spread to my brain or spinal cord.

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My follicular lymphoma has become more aggressive or is grade 3b.

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I do not have any uncontrolled illnesses that would affect my participation in the study.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 86 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 86 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 86 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase 1: Number of Participants Experiencing Dose Limiting Toxicity (DLT)

Phase 1: Number of Participants Who Discontinued Study Treatment Due to an AE

Phase 1: Number of Participants Who Experienced an Adverse Event (AE)

+2 more

Secondary study objectives

Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC 0-24hrs)of Nemtabrutinib

Maximum Concentration (Cmax) of Nemtabrutinib

Phase 2: Expansion Cohorts A, B, H: Duration of Response (DOR) per iwCLL Criteria as Assessed by the Investigator

+7 more

Trial Design

10Treatment groups

Experimental Treatment

Group I: Phase 2: Expansion Food Effect Cohort IExperimental Treatment1 Intervention

B-cell Non-Hodgkin's lymphoma (NHL), CLL/SLL and WM participants receive up to 65 mg of nemtabrutinib fasted (1 hour prior to or 2 hours after meal) and non-fasted per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).

Group II: Phase 2: Expansion Cohort HExperimental Treatment1 Intervention

Waldenström macroglobulinemia (WM) participants who have failed at least 2 prior systemic therapies receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).

Group III: Phase 2: Expansion Cohort GExperimental Treatment1 Intervention

High-grade B-cell lymphoma (BCL) participants who have failed at least 2 prior systemic therapies and have known MYC and BCL2 and/or BCL6 translocations confirmed by flourescence in situ hybridization (FISH) or overexpression by immunohistochemistry (IHC) receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).

Group IV: Phase 2: Expansion Cohort FExperimental Treatment1 Intervention

Marginal Zone Lymphoma (MZL) participants who have failed at least 2 prior systemic therapies receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).

Group V: Phase 2: Expansion Cohort EExperimental Treatment1 Intervention

Mantle Cell Lymphoma (MCL) participants who have failed at least 2 prior systemic therapies receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).

Group VI: Phase 2: Expansion Cohort DExperimental Treatment1 Intervention

Follicular Lymphoma (FL) participants who have failed at least 2 prior systemic therapies and are histology grade 1, 2, or 3A receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).

Group VII: Phase 2: Expansion Cohort CExperimental Treatment1 Intervention

Richter's transformation (RT) participants who have failed at least one prior therapy receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).

Group VIII: Phase 2: Expansion Cohort BExperimental Treatment1 Intervention

R/R CLL/SLL participants who have failed or were intolerant to a BTKi with documentation of the absence of BTK mutation on C481 residue receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).

Group IX: Phase 2: Expansion Cohort AExperimental Treatment1 Intervention

Relapsed/Refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (R/R CLL/SLL) participants with at least 2 prior systemic therapies and previously treated with a covalent Bruton's tyrosine kinase inhibitor (BTKi) who must have a documented BTK mutation on C481 residue receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until progressive disease (PD), unacceptable adverse events (AEs), or discontinuation at investigator's discretion (up to approximately 64 months).

Group X: Phase 1: Dose Escalation and Determination of RP2DExperimental Treatment1 Intervention

Phase I: Dose Escalation and determination of RP2D, multiple dose levels of nemtabrutinib to be evaluated (Up to approximately 22 months).

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for lymphoma include Bruton tyrosine kinase (BTK) inhibitors, monoclonal antibodies, and chemotherapy. BTK inhibitors, such as Nemtabrutinib, work by blocking the BTK enzyme, which is crucial for the survival and proliferation of B-cells, including malignant B-cells in lymphoma. This inhibition leads to the death of cancerous cells and halts disease progression. Monoclonal antibodies target specific proteins on the surface of lymphoma cells, marking them for destruction by the immune system. Chemotherapy uses cytotoxic drugs to kill rapidly dividing cells, including cancer cells. These mechanisms are vital for lymphoma patients as they directly target the cancer cells, reduce tumor burden, and improve survival rates.

[Staging and Treatment Response Evaluation in Malignant Lymphomas - Czech Lymphoma Study Group Recommendations According to Criteria Revised in 2014 (Lugano Classification)].