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

Recruiting now · Phase 2

Conditions studied: Recurrent Mantle Cell Lymphoma, Refractory Mantle Cell Lymphoma

In brief

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.

Key facts

Study ID

NCT07673367

Run by

Vanderbilt-Ingram Cancer Center

People needed

25

Starts

2026-07-31

Expected to finish

2032-07-31

Last updated by the study team

2026-08-05

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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
• Participants with HIV are eligible if they meet ALL of the following criteria:
• The CD4 count is ≥ 350 cells/uL at screening
• The HIV viral load is below the detectable level as per locally available testing
• Are on a stable anti-retroviral therapy (ART) regimen for at least 4 weeks prior to study entry
• NOTE: ART includes drugs, which are NOT strong cytochrome P450 (CYP)3A4 inducers (participants receiving ART that are strong CYP3A4 inducers are not eligible to be included in the study)
• HIV screening tests are not required unless:
• Known history of HIV infection
• As mandated by local health authority or institutional standards
• Are compliant with their ART
• Adequate organ function as defined. Specimens must be collected within 10 days prior to treatment initiation with nemtabrutinib in both pre-CAR and post-CAR T phase

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:
• P-glycoprotein (P-gp) substrates with a narrow therapeutic index
• CYP3A strong inducers
• CYP3A strong inhibitors
• NOTE: A washout period of at least 5 times the half-life after the last dose of any of the above treatments is required for a participant to be eligible for study enrollment
• Has received prior systemic anti-cancer therapy including investigational agents within 2 weeks or 5 half-lives before start of study treatment (whichever is shorter). Subjects can be screened pending required wash-out period before starting nemtabrutinib
• Has received prior radiotherapy within 2 weeks of start of study intervention or has radiation-related toxicities requiring corticosteroids
• NOTE: Two weeks or fewer of palliative radiotherapy for non-CNS disease, with a 1-week washout, is permitted
• Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed
• Is currently enrolled on another therapeutic clinical trial. Concurrent enrollment on another therapeutic clinical trial or any trial designed to impact the efficacy of anti-cancer therapy is prohibited
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration

Where it is running

• Vanderbilt University/Ingram Cancer Center — Nashville, Tennessee, United States (enrolling)

Full record on ClinicalTrials.gov

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