Nemtabrutinib With CAR T Therapy in Relapsed/Refractory Mantle Cell Lymphoma

NCT07673367 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: VICC-VCCTT23481
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests the effect of nemtabrutinib in combination with brexucabtagene autoleucel (brexu-cel) in treating patients with mantle cell lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Nemtabrutinib, a BTK inhibitor, may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chimeric antigen receptor (CAR) T-cell therapy, such as brexu-cel, is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Chemotherapy, such as fludarabine and cyclophosphamide, are given before CAR T cell therapy to help kill cancer cells in the body and help make room for the CAR T cells. Giving nemtabrutinib in combination with brexu-cel may be safe, tolerable, and/or effective in treating patients with relapsed or refractory mantle cell lymphoma.

Conditions

Recurrent Mantle Cell Lymphoma; Refractory Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival after brexucabtagene autoleucel (brexu-cel) infusion in relapsed/refractory mantle cell lymphoma

  Will be analyzed using Kaplan-Meier product limit methods to estimate the survival distribution, median time-to-event with 95% confidence interval, patients at risk, patients with an event, patients censored and survival probabilities at selected time points. Kaplan-Meier methods will be used to estimate the event-free curves and corresponding quartiles (including the median).

  From the day of brexu-cel infusion to the earlier of documentation of objective disease progression, initiation of any non-protocol anti-lymphoma therapy or death from any cause, assessed up to 5 years

Secondary Outcomes (3)

• Estimate complete response (CR) rate following the infusion of CAR T cell

  Day 28 until up to one year after CAR T infusion

• Number of Adverse Events After CAR-T Cell Infusion with nemtabrutinib

  Up to 2 years from CAR T infusion

• Overall survival after CAR T infusion

  Day of CAR T infusion until up to 5 years

Study Arms (1)

Nemtabrutinib + brexu-cel

EXPERIMENTAL

PRE-CAR T PHASE (4-5 WEEKS): Starting 2 weeks before undergoing apheresis, patients receive nemtabrutinib orally (PO) once daily (QD) on days -40 to -6 in the absence of disease progression or unacceptable toxicity. Patients receive lymphodepleting chemotherapy fludarabine and cyclophosphamide on days -5 to -3. CAR T INFUSION PHASE (4-5 WEEKS): Patients receive brexu-cel IV on day 0. POST CAR T PHASE (UP TO 24 MONTHS): Starting around day 28 or later after brexu-cel infusion, patients without progressive disease (PD) receive nemtabrutinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 24 cycles (2 years) in the absence of disease progression or unacceptable toxicity.

Drug: Nemtabrutinib; Drug: Brexucabtagene autoleucel ( other names: brexu-cel , Tecartus)

Interventions

Nemtabrutinib DRUG

Given PO

Nemtabrutinib + brexu-cel

Brexucabtagene autoleucel ( other names: brexu-cel , Tecartus) DRUG

single IV administration

Nemtabrutinib + brexu-cel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of relapsed or refractory mantle cell lymphoma who meets institutional eligibility criteria to receive standard of care brexu-cel therapy
• Is an individual of any sex/gender, who are at least 18 years of age on the day of signing informed consent with confirmed diagnosis of R/R MCL will be enrolled in this study
• The participant (or legally acceptable representative if applicable) has provided documented informed consent/assent for the trial
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention
• The ability to swallow and retain oral medication
• \* NOTE: Administration of nemtabrutinib is not permitted through a percutaneous endoscopic gastro-jejunal (J-PEG) tube
• Participants who are hepatitis B virus surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to allocation
• \* Note: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. Hepatitis B screening tests should include HBsAg and anti-HBV. Hepatitis B screening tests are not required unless:
• Known history of HBV infection
• As mandated by local health authority
• Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
• Participants must have completed curative anti-viral therapy at least 4 weeks prior to allocation
• Hepatitis C screening tests are not required unless:
• Known history of HCV infection
• As mandated by local health authority

You may not qualify if:

• Gastrointestinal dysfunction that may affect drug absorption (e.g., gastric bypass surgery, gastrectomy)
• Diagnosis of Richter transformation including any history of Richter's transformation
• Active central nervous system (CNS) involvement with lymphoma. Previously treated CNS disease allowed as long as confirmed disease control based on imaging and negative cerebrospinal fluid (CSF) cytology
• Active infection requiring systemic therapy, including IV antibiotics during screening. Participants may be rescreened following completion of IV antibiotic course (24 hour washout period required). PO antibiotics are allowed if infection is considered controlled by treating physician
• AIDS defining opportunistic infection in the past 12 months prior to screening
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
• Corrected QT interval (QTc) prolongation (defined as a Fridericia's formula-corrected QT interval \[QTcF\] \> 450 msecs) or other significant electrocardiogram (ECG) abnormalities including second degree atrioventricular (AV) block type II, third degree AV block, or bradycardia (ventricular rate less than 50 beats/min)
• Known allergy/sensitivity (≥ grade 3) to nemtabrutinib or any of the excipients
• History of severe bleeding disorder defined as an ongoing congenital or acquired condition that leads to an increased likelihood of bleeding
• History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
• \* NOTE: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ of bladder or cervix
• A POCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• \* Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication
• Patients with refractory MCL to non-covalent BTK inhibitor such as pirtobrutinib or nemtabrutinib. Patients who have relapsed or refractory MCL after prior covalent BTK inhibitors are allowed. Patients who have received prior non-covalent BTK inhibitors and achieved at least partial response are allowed
• Currently being treated with the following drugs:

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

brexucabtagene autoleucel

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Bhagirathbhai Dholaria

  Vanderbilt University/Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vanderbilt-Ingram Services for Timely Access

CONTACT

800-811-8480; cip@vumc.org

Vanderbilt-Ingram Services Timely Access

CONTACT

cip@vumc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2026
• First Posted: June 29, 2026
• Study Start: July 31, 2026
• Primary Completion (Estimated): July 31, 2031
• Study Completion (Estimated): July 31, 2032
• Last Updated: July 1, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)