Nemtabrutinib and Lisocabtagene Maraleucel for the Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• Confirmed diagnosis of CLL/SLL per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) classification
• Measurable disease by imaging (lymph node [LN] > 1.5cm) or absolute lymphocyte count (ALC) (> 5000/μL) or marrow involvement of at least 30% by flow cytometry
• Eligible for lisocabtagene maraleucel (liso-cel) as standard-of-care per Food and Drug Administration (FDA) label for CLL/SLL
• At least 18 years of age at time of study enrollment
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• 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 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 randomization
• 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
• Absolute neutrophil count (ANC) ≥750/μL (or ≥500/μL in participants with documented bone marrow involvement)
• Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed
• Hemoglobin ≥ 8 g/dL
• Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed
• Platelets ≥50 000/μL (or ≥30 000/μL in participants with documented bone marrow involvement)
• Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed
• Creatinine ≤ 1.5 × upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or CrCl) ≥ 30 mL/min for participant with creatinine levels > 1.5 × institutional ULN
• Creatinine clearance (CrCl) should be calculated per institutional standard
• Total bilirubin ≤ 1.5 × ULN OR direct bilirubin ≤ ULN for participants with total bilirubin levels > 1.5 × ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) ≤ 2.5 × ULN (≤ 5 × ULN for participants with liver metastases)
• International normalized ratio (INR) OR prothrombin time (PT) ≤ 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Cardiac (echocardiogram [Echo] or multi-gated acquisition scan [MUGA]) ejection fraction ≥ 40%

You cannot join if

• Diagnosis of Richter Transformation
• Clinically significant (symptomatic) central nervous system (CNS) involvement at time of study enrollment. Previously treated CNS disease is allowed if the participant is asymptomatic. Incidental findings including positive cerebral spinal fluid (CSF) studies are not exclusionary
• Active infection and uncontrolled infection
• Active HBV/hepatitis C virus (HCV) infection
• Participants must have completed curative anti-viral therapy for HCV at least 4 weeks prior to study enrollment
• Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to study enrollment
• 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
• HIV with a detectable viral load or a CD4 count ≤ 350 cells/µL at time of screening
• Participants with HIV who do not meet the above criteria are eligible if they are on a stable antiretroviral therapy (ART) regimen (ART must not be strong CYP3A4 inducers) for at least 4 weeks prior to study entry and are compliant with ART are eligible
• Patients with an AIDS defining opportunistic infection in the past 12 months prior to screening
• Gastrointestinal dysfunction that may affect drug absorption (e.g., gastric bypass surgery, gastrectomy)
• 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 QTc > 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 to nemtabrutinib or any of the excipients
• Known prior progressive disease while on nemtabrutinib
• NOTE: Refer to the investigator's brochure (IB) for details regarding prior recipients of nemtabrutinib
• History of severe bleeding disorder defined as an ongoing congenital or acquired condition that leads to an increased likelihood of bleeding
• Known additional malignancy that is progressing or has required active treatment within the past 2 years
• NOTE: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. Participants with low-risk, early-stage prostate cancer (T1-T2a, Gleason score ≤6, and PSA < 10ng/mL), either treated with definitive intent or untreated in active surveillance with stable disease, are not excluded
• A participant of childbearing potential (POCBP) who has a positive urine pregnancy test within 72 hours prior to study enrollment. 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 participant to start receiving study medication
• Need or anticipation of need for additional bridging therapy in addition to nemtabrutinib
• Palliative radiation therapy for less than 2 weeks or the use of prednisone 30mg (or the prednisone equivalent) for a maximum of 5 days is allowed and is not exclusionary
• Currently being treated with the following drugs:
• 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 a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of inactivated 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
• Has not adequately recovered after 4 weeks from major surgery or has ongoing surgical complications
• Note: Biopsy and placement of central venous access devices are not considered major surgery
• Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Any condition or history that the study investigator deems not in the best interest of the patient to participate

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

nemtabrutinib. An orally available reversible inhibitor of Bruton's tyrosine kinase (BTK; Bruton agammaglobulinemia tyrosine kinase), with potential antineoplastic activity. Upon administration, nemtabrutinib non-covalently binds to and inhibits the activity of both the wild-type and the C481S mutated form of BTK, a resistance mutation in the BTK active site in which cysteine is substituted for serine at residue 481. This prevents the activation of the B-cell antigen receptor (BCR) signaling pathway and BTK-mediated activation of downstream survival pathways. This leads to an inhibition of the growth of malignant B cells that overexpress BTK. Compared to other BTK inhibitors, nemtabrutinib does not require interaction with the BTK C481 site and inhibits the proliferation of cells harboring the BTK C481S mutation. BTK, a member of the Src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed or mutated in B-cell malignancies; it plays an important role in the development, activation, signaling, proliferation and survival of B lymphocytes. NCI Drug Dictionary

lisocabtagene maraleucel. A preparation of a defined ratio of CD4+ and CD8+ autologous T lymphocytes transduced with a lentiviral vector expressing a chimeric antigen receptor (CAR) containing an anti-CD19 single chain variable fragment (scFv) fused to the signaling domain of 4-1BB (CD137), the zeta chain of the TCR/CD3 complex (CD3-zeta), and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, lisocabtagene maraleucel is directed to and induces selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. Devoid of both ligand binding domains and tyrosine kinase activity, the expressed EGFRt both facilitates in vivo detection of the administered, transduced T cells and can promote elimination of those cells through a cetuximab-induced antibody dependent cellular cytotoxicity (ADCC) response. The 4-1BB costimulatory signaling domain enhances both proliferation of T cells and antitumor activity. NCI Drug Dictionary

Treatments listed in the registry

• Nemtabrutinib (Drug): Given PO
• Lisocabtagene Maraleucel (Biological): Given IV

Na · Single Group · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• biopsy: Part of the study plan
• bone marrow: Part of the study plan
• blood samples: Part of the study plan
• CT scans: Part of the study plan
• PET scans: Part of the study plan
• echocardiogram: Part of the study plan
• leukapheresis: Part of the study plan

Main goals

• Complete response (CR) (Up to 5 years after completion of study treatment)

Other goals

• Overall response rate
• Overall survival (OS)
• Progression free survival (PFS)
• Time to response (TTR)
• Time to next treatment (TTNT)
• Duration of response (DoR)
• CR on positron emission tomography/computed tomography by Lugano criteria
• Incidence of adverse events
• Incidence of dose-limiting toxicity (DLT)
• Incidence of cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity (ICANS)
• Time to CRS or ICANS onset
• Time from CRS or ICANS onset to resolution

Planned enrollment: 20 (estimated).

• Fred Hutch/University of Washington Cancer Consortium, Seattle, Washington

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT07194980
• NCI Drug Dictionary: C138066
• NCI Drug Dictionary: C125192

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Oct 28, 2026. Public record; not medical advice.