Pirtobrutinib and Epcoritamab vs R-(Mini)-CHOP for DLBCL-type Richter Transformation in older or frail adults

Inclusion Criteria:

1. Age ≥80 years OR considered frail defined by a frailty score of \>2 on the FRAIL scale via the patient´s assessment
2. Has documented treatment-naïve CLL or small lymphocytic lymphoma (SLL) according to iwCLL 2018 criteria3
3. CLL/SLL requiring treatment according to the iwCLL 2018 criteria3
4. Adequate marrow function independent of growth factor or transfusion support within 2 weeks of screening as follows, unless cytopenia is due to marrow involvement of CLL:

   * Absolute neutrophil count ≥ 1.0 × 10\^9/L
   * Platelet counts ≥ 30 × 10\^9/L; in cases of thrombocytopenia clearly due to marrow in-volvement of CLL (per the discretion of the investigator); platelet count should be ≥ 10 × 10\^9/L if there is bone marrow involvement
   * Total haemoglobin ≥ 9 g/dL (without transfusion support, unless anaemia is due to mar-row involvement of CLL)
5. Adequate liver function as indicated by a total bilirubin, AST, and ALT ≤2 times the institutional upper limit of normal (ULN) value unless directly attributable to the patient's CLL or Gilbert's syndrome
6. Adequate renal function defined by a value ≥30 mL/min, determined either by creatinine clearance directly measured with a 24-hour urine collection or via estimated GFR calculated according to the CKD-EPI equation or Cystatin C measurements (e.g. in sarcopenic patients).
7. Negative serological testing for hepatitis B (HBsAg negative and anti-HBc negative; patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA PCR is performed repeatedly until 6 months after last month of treatment), negative testing for hepa-titis C RNA within 6 weeks prior to registration
8. Life expectancy ≥ 3 months
9. In case of a recent previous (i.e. debulking) treatment, patients must have recovered from acute toxicities and treatment regimen must be stopped within the following time periods be-fore start of the study treatment in the CLL-Frail2 trial:

   * chemotherapy ≥ 28 days
   * antibody treatment ≥ 14 days
   * corticosteroids may be applied until the start of the study therapy; these have to be re-duced to an equivalent of ≤ 20mg prednisolone per day during treatment
10. Signed informed consent and, in the investigator's judgment, able to comply with the study protocol
11. Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

* 1\. Previous CLL-directed therapies 2. Transformation of CLL to aggressive NHL (Richter's transformation or pro-lymphocytic leu-kaemia) 3. Patients with a history of confirmed progressive multifocal leukoencephalopathy (PML) 4. Uncontrolled autoimmune condition 5. Malignancies other than CLL currently requiring systemic therapies (unless the malignant dis-ease is in a stable remission at the discretion of the treating physician) 6. Uncontrolled infection currently requiring systemic treatment 7. Any serious medical condition or abnormality in clinical laboratory tests that, in the investiga-tor's judgment, precludes the patient's safe participation in and completion of the study 8. Requirement of treatment with any moderate or strong CYP3A4 inhibitor or strong CYP3A4 inducer (≤ 14 days or 5 half-lives, whichever is shorter) before the first dose of study drug, or requiring ongoing treatment with a moderate or strong CYP3A inhibitor or a strong CYP3A in-ducer.

  9\. Requirement of therapy with phenprocoumon or other vitamin K antagonists 10. Known active infection with HIV, or serologic status reflecting active hepatitis B or C infection as follows:
  * Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible if hepatitis B virus (HBV) DNA is undetectable (\< 20 IU), and if they are willing to undergo monitoring for HBV reactivation
  * Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable 11. Major surgery within 4 weeks of the first dose of study drug 12. Any uncontrolled or clinically significant cardiovascular disease including the following:
  * New York Heart Association class III or IV congestive heart failure
  * History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricu-lar fibrillation, torsades de pointes) 13. History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand dis-ease if not CLL/SLL related, or history of spontaneous bleeding requiring blood transfusion or other medical intervention 14. Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery proce-dures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.

    15\. Use of investigational agents, e.g. monoclonal antibodies or other experimental drugs within clinical trials, which might interfere with the study drug within 28 days (or 5 times half-life \[t1/2\] of the compound, whichever is longer) prior to registration 16. Known hypersensitivity to zanubrutinib or sonrotoclax or any of the excipients 17. Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment) 18. Fertile men or women of childbearing potential unless:
  * surgically sterile or ≥ 2 years after the onset of menopause, or
  * willing to use two methods of reliable contraception including one highly effective contra-ceptive method (Pearl Index \<1) and one additional effective (barrier) method during study treatment and for 7 days after sonrotoclax and 30 days after zanubrutinib respec-tively 19. Vaccination with a live vaccine \<28 days prior to registration 20. Legal incapacity 21. Prisoners or subjects who are institutionalized by regulatory or court order 22. Persons who are in dependence to the sponsor or an investigator