Clonal Dynamics of Chronic Lymphocytic Leukaemia Treated With Pirtobrutinib After Previous Treatment With Zanubrutinib

Inclusion Criteria: 1. Patient has provided written informed consent using the PIPOZA Patient Information and Consent Form (PICF) 2. Confirmed diagnosis of CLL according to iwCLL 2018 criteria, also including CLL with atypical immunophenotype 3. Prior systemic therapy, which must include zanubrutinib as the most recent prior line of therapy. Patients must have received at least one cycle (28 days) of zanubrutinib 4. Patients must have an indication for second- or subsequent-line treatment in the opinion of the investigator as defined by iwCLL 2018 criteria, including: * Where the original indication for treatment has not resolved with initial therapy and it is considered reasonable to initiate second-line treatment without waiting for formal disease progression to be manifest * Where the rate of disease progression is considered rapid, and initiation of subsequent therapy is considered acceptable before formal progression where there is substantial persisting disease burden 5. Age 18 years of age or older at time of signing the PICF 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 7. Must have adequate bone marrow function, as defined below: * Absolute neutrophil count \> 0.75 × 109/L; if marrow is known to be infiltrated by CLL, granulocyte-colony stimulating factor (G-CSF) support may be used to achieve eligibility criteria * Platelets ≥ 30 × 109/L independent of transfusions within 7 days prior to screening assessment * Haemoglobin ≥ 70 g/L independent of transfusions within 7 days prior to screening assessment 8. Normal hepatic function defined as: * Total bilirubin ≤ 1.5× upper limit of normal (ULN) or ≤ 3.0 x ULN with documented liver involvement and/or Gilbert's Disease * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 3.0 × ULN or ≤ 5.0 × ULN with documented liver involvement 9. Adequate renal function defined as creatinine clearance of \> 30 mL/minute calculated by Cockroft-Gault formula or using biochemical or nuclear medicine techniques 10. Ability to swallow tablets 11. Patients must have had a zanubrutinib washout period of at least 24 hours prior to the planned start date of pirtobrutinib on Day 1 Cycle 1 12. Prior treatment-related adverse events must have recovered to Grade ≤ 1 or pretreatment baseline with the exception of alopecia and Grade 2 peripheral neuropathy 13. Women of childbearing potential defined as not postmenopausal for at least 2 years or surgically sterile must have a negative serum pregnancy test documented within 14 days prior to planned started date of pirtobrutinib on Day 1 Cycle 1 14. Men with partners of childbearing potential or women of childbearing potential must agree to use a highly effective contraceptive method of birth control during study treatment and for at least 6 months following the last dose of study drug. Sperm donation is prohibited during the duration of participation in this study and for 6 months after the last dose of study drug. Acceptable methods of birth control are: * Combined estrogen and progestin containing hormonal contraception associated with inhibition of ovulation given orally, intravaginally, or transdermally * Progestin-only hormonal contraception associated with inhibition of ovulation given orally, by injection, or by implant * Intrauterine device Intrauterine hormone-releasing system * Bilateral tubal occlusion * Vasectomised partner * Sexual abstinence: Considered a highly effective method only if defined as refraining from heterosexual intercourse during an entire period of risk associated with the study treatment. The reliability of sexual abstinence needs will be evaluated in relation to the duration of the study and to the usual lifestyle of the patient 15. The patient understands the purpose of the trial and procedures required for the trial which includes compliance with the protocol requirements and restrictions listed in the PICF and in this protocol Exclusion Criteria: 1. Known or suspected Richter's Transformation to diffuse large B-cell lymphoma, prolymphocytic leukaemia, or Hodgkin lymphoma at any time prior to registration 2. Known or suspected history of central nervous system involvement 3. History of allogeneic or autologous stem cell transplant or chimeric antigen receptor T-cell (CAR-T) therapy within the past 60 days and/or with any of the following: * Active graft versus host disease * Cytopenias from incomplete blood cell count recovery post-transplant or CAR-T therapy * Need for anti-cytokine therapy for toxicity from CAR-T therapy; residual symptoms of neurotoxicity Grade \> 1 from CAR-T therapy * Ongoing immunosuppressive therapy 4. Positive serology for human immunodeficiency virus (HIV) test in Screening 5. Concurrent anticancer therapy 6\. Use of ≥ 20 mg prednisone QD or equivalent dose of steroid per day within 7 days prior to the planned pirtobrutinib start date on Day 1 Cycle 1. Patients may not be on prednisone of any dose intended for antineoplastic use 7. Vaccination with a live vaccine within 28 days prior to registration 8. Prolongation of the corrected QT interval using the Fredericia formula (QTcF) \> 470 msec (QTcF is calculated using Fridericia's Formula: QTcF = QT / \[RR0.33\]) * Correction of suspected drug induced QTcF prolongation can be attempted at the investigator's discretion and only if clinically safe to do so with either discontinuation of the offending drug or switch to another drug not known to be associated with QTcF prolongation * Manual correction for underlying bundle branch block is allowed Note: Patients with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker 9. Female patient who is pregnant or plans to become pregnant within 1 month after the last dose of study treatment 10. Female patient who is lactating or plans to breastfeed during the study or within 1 week after th