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Comparison of rocbrutinib versus pirtobrutinib in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma

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What is this trial about?

A plain-language summary of the goals, design and what participants do

Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma are types of blood‑cell cancers that can return or keep growing after earlier treatment with drugs that permanently block a protein called BTK. This study examines two oral medicines taken as tablets once a day: rocbrutinib (LP-168) and pirtobrutinib. Both drugs belong to a class that targets the same protein pathway but have different chemical structures.

The purpose of the study is to compare how well the two medicines work and how safe they are in people whose disease has come back or did not respond after previous cBTKi therapy. Participants will be randomly assigned to receive either rocbrutinib or pirtobrutinib, will take the assigned pill daily, and will attend regular clinic visits where doctors will perform blood tests and imaging scans to check whether the disease stays stable or improves. The study will follow participants for several years to record the time without disease worsening, overall survival, and any side effects that may occur.

The research process

The trial runs in 8 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Randomization to Treatment Group

    After joining the study, you will be assigned by chance to receive either rocbrutinib (the test medication) or pirtobrutinib (the comparator medication). The assignment is done by the study team and you will know which medication you will take.

  2. Step 2

    Receive Study Medication

    You will be given tablets that you must take by mouth. Each tablet contains 200 mg of the active substance (rocbrutinib or pirtobrutinib depending on your group). The tablets are film‑coated and are provided in a supply that lasts until your next clinic visit.

  3. Step 3

    Take Medication Daily

    You will take one tablet each day, at the same time each day, unless the study doctor tells you otherwise. The medication is taken with water and does not require any special preparation.

  4. Step 4

    Attend Scheduled Clinic Visits

    You will visit the study clinic at regular intervals that are defined by the study protocol. During each visit you will meet the study staff, who will check your health, record any side effects, and confirm that you are taking the medication as instructed.

  5. Step 5

    Undergo Disease Assessments

    At the clinic visits you will have tests that evaluate the status of your chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). These assessments may include physical examinations, imaging scans, and blood tests that help determine whether the disease is progressing or responding to treatment. The results are reviewed by an independent review committee (IRC) and by the investigators (INV).

  6. Step 6

    Provide Blood Samples for Drug Level Testing

    During some visits you will give a small amount of blood so the laboratory can measure the concentration of rocbrutinib in your plasma. These sparse pharmacokinetic (PK) samples help researchers understand how the drug is absorbed and cleared from your body.

  7. Step 7

    Report Any Side Effects

    You will be asked to describe any new symptoms, feelings, or laboratory changes you notice. All side effects are recorded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0), which classifies the severity of each event.

  8. Step 8

    Continue Treatment Until End of Study or Discontinuation

    You will keep taking the assigned medication each day until the study ends, you experience an event that requires stopping treatment, or your doctor decides that you should leave the study. The overall study period may last several years, with the estimated end date of the trial being July 30 2030.

Who can join the trial?

14 criteria

  • You must be 18 years old or older at the time of screening.
  • You must have a confirmed diagnosis of relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) based on tissue or cell testing.
  • You need at least one measurable tumor, such as a lymph node that is at least 1.5 cm long (or an extranodal lesion larger than 1.0 cm for SLL).
  • You must have previously received a covalent BTK (Bruton’s tyrosine kinase) inhibitor, either an investigational or approved drug, alone or with other treatments.
  • Your doctor must know whether you have a 17p chromosome deletion, which is checked with a test called FISH (fluorescence in‑situ hybridisation).
  • Your doctor must also know whether you have a TP53 gene mutation, which is checked with a test called NGS (next‑generation sequencing).
  • Your overall health must be rated as ≤ 2 on the ECOG performance‑status scale (Eastern Cooperative Oncology Group), meaning you are fully active or able to do light work.
  • You should be expected to live at least 24 weeks (about six months) from the start of the study.
  • Your blood‑clotting, kidney and liver function must be within normal limits: clotting times (APTT and PT) no more than 1.5 × the upper normal range; kidney clearance (creatinine clearance) at least 30 mL/min; liver enzymes (AST and ALT) no higher than three times the upper normal range; and bilirubin no higher than 1.5 × the upper normal range (except in certain harmless conditions).
  • Your bone‑marrow function must be adequate: white‑blood‑cell count (ANC) at least 1,000 per microliter unless low because the disease heavily involves the marrow; platelet count at least 50,000 per microliter (or at least 30,000 if low due to disease); and hemoglobin at least 8.0 g/dL without a blood transfusion in the past two weeks.
  • If you are a female who could become pregnant, or a male who is not surgically sterile, you must use one of the listed birth‑control methods (total abstinence, a partner who has had a sterilizing procedure, an intrauterine device, or hormonal contraception started at least one month before the study) throughout the study and for 90 days after the last dose.
  • Females who could become pregnant must have a negative pregnancy test before the first dose (blood test within 7 days or urine test on the day of dosing) and must repeat testing if any test is unclear.
  • Male participants must not donate sperm from the first dose until 90 days after the last dose of the study drug.
  • You must be able to read, understand, and voluntarily sign an informed‑consent form approved by an ethics committee before any study procedures.

Who cannot join the trial?

30 criteria

  • Prior use of a non‑covalent BTK inhibitor (ncBTKi) or a BTK‑PROTAC drug.
  • History of Richter’s transformation (an aggressive lymphoma that can develop from CLL).
  • Confirmed prolymphocytic leukemia (a different, more aggressive blood cancer).
  • Received any cancer treatment (chemotherapy, radiation, hormonal therapy, targeted drugs, etc.) within the last 14 days or before the study drug has cleared, and has not recovered to only mild side‑effects.
  • Taken strong CYP3A4 or CYP2C8 interacting medicines (such as certain antifungals, antibiotics, rifampin, carbamazepine, St. John’s wort) within 14 days before the first dose.
  • Taken high‑dose steroids (equivalent to more than 20 mg prednisone per day) for cancer, or strong immunosuppressive drugs, within 7 days before the first dose (except a short steroid course allowed for symptom control).
  • Require ongoing treatment with strong CYP3A4 inhibitors or inducers, or drugs that are affected by CYP2C8.
  • Require medicines that can lengthen the heart’s QTc interval or cause a dangerous rhythm called torsade de pointes.
  • Are taking warfarin or other vitamin K‑blocking blood thinners.
  • Need regular use of acid‑reducing drugs (proton‑pump inhibitors, H2 blockers, antacids) that cannot be stopped or timed as required by the study.
  • Require immediate cytoreduction (rapid tumor‑killing therapy) at study start (except a brief steroid course is allowed).
  • Have a significant history of kidney, nerve, mental health, lung, hormone, metabolism, immune, heart, or liver disease that the doctor feels would make participation unsafe.
  • Have conditions that make swallowing the study drug difficult or that greatly affect drug absorption (e.g., severe stomach or bowel disease, removal of part of the stomach or small intestine, ulcerative colitis, inflammatory bowel disease, bowel blockage).
  • Have had a stem‑cell transplant (autologous or allogeneic) within 60 days, are on immunosuppressive drugs after transplant, or have active graft‑versus‑host disease (GVHD) unless specific criteria are met.
  • Underwent major surgery or suffered serious injury within 14 days before the first dose.
  • Had another active cancer within the past year, except for certain skin cancers, in‑situ cervical cancer, or cancers that are stable and not expected to affect survival.
  • Have serious uncontrolled systemic illnesses such as active infections, uncontrolled high blood pressure, diabetes, unstable chest pain, heart failure, need for continuous oxygen, severe clotting problems, major bleeding, or severe liver, kidney, or metabolic disease.
  • Have ongoing drug‑induced liver injury.
  • Have recent major heart problems (uncontrolled or symptomatic irregular heartbeat, heart failure, heart attack, stroke) within 180 days, or have very low heart‑pump function (ejection fraction ≤ 40%) or advanced heart‑failure class.
  • Have a significant abnormal heart test (ECG) such as second‑degree AV block type II, third‑degree block, serious slow heart rate, or a QTc interval ≥ 480 ms.
  • Have active disease in the central nervous system (brain or spinal cord) or a history of CNS involvement that is not well controlled.
  • Have uncontrolled infections (bacterial, fungal, viral, parasitic), uncontrolled HIV, active hepatitis B or C, unexplained fever above 38.3 °C, or active cytomegalovirus infection.
  • Received live attenuated vaccines within 4 weeks before the first dose or plan to receive them during the study or within 4 weeks after the study ends.
  • Have bleeding disorders (such as von Willebrand disease, hemophilia A or B) or a history of brain bleeding within 180 days.
  • Have an uncontrolled autoimmune disease that requires more than 20 mg prednisone (or equivalent) daily within 4 weeks before starting the study.
  • Are pregnant.
  • Are breastfeeding or plan to breastfeed from the first dose until one week after the last dose.
  • Are allergic or intolerant to rocbrutinib, pirtobrutinib, or any of their ingredients.
  • Have eaten grapefruit, grapefruit juice, Seville oranges, or star fruit within 3 days before the first dose.
  • Have any other condition that the investigator judges makes participation unsuitable.
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Investigated drugs

  • pirtobrutinib

    is an oral medication taken as a tablet that belongs to a class of drugs called BTK inhibitors. It works by blocking a protein (BTK) that helps certain cancer cells grow and survive, especially in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). In this trial, pirtobrutinib is used as the standard treatment (comparator) to see how well the new drug performs against it.

  • rocbrutinib

    is an oral tablet being studied as a new treatment for CLL and SLL. Like pirtobrutinib, it targets the BTK protein, but it is a different molecule that may work better in patients whose disease has already been treated with other BTK inhibitors. In this trial, rocbrutinib is the experimental drug (test) whose ability to keep the disease from getting worse is being compared with pirtobrutinib.

What is already known about the treatment

  • Pirtobrutinib

    This medication is taken by mouth as a film‑coated tablet, usually 200 mg once daily. It is an approved drug for adults with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma after prior therapy. Pirtobrutinib works by reversibly attaching to the Bruton’s tyrosine kinase (BTK) enzyme, stopping the signal that tells cancer B‑cells to grow. It belongs to the class of reversible BTK inhibitors, a type of small‑molecule targeted therapy.

  • Rocbrutinib

    Rocbrutinib is also an oral tablet taken at a dose of 200 mg each day, but it is still under investigation and not yet approved for general use. It is being studied for the same types of blood cancers (relapsed or refractory CLL/SLL) in patients who have already received covalent BTK inhibitors. The drug binds permanently to the BTK enzyme, blocking the pathway that drives malignant B‑cell growth. Rocbrutinib is classified as an investigational covalent BTK inhibitor, a small‑molecule targeted agent.

Investigated diseases

  • Chronic Lymphocytic Leukemia (CLL)

    Chronic lymphocytic leukemia is a cancer of the white blood cells that starts in the bone marrow and leads to an excess of mature‑looking B‑lymphocytes in the blood. These cells grow slowly at first but can accumulate over time, crowding out normal blood cells. The disease may spread to the spleen, liver, and lymph nodes, causing them to enlarge. As the number of abnormal cells rises, the blood count can change and the marrow becomes less able to produce healthy cells. In some patients the disease becomes more aggressive, with faster growth of the leukemia cells.

  • Small Lymphocytic Lymphoma (SLL)

    Small lymphocytic lymphoma is a cancer that primarily involves the lymph nodes and other lymphoid tissues, using the same type of B‑cell as CLL. It presents as enlarged, painless lymph nodes that may increase in size gradually. Over time the lymphoma can involve the bone marrow and blood, essentially turning into CLL. The abnormal cells can also appear in the spleen and liver, leading to organ enlargement. The disease may progress slowly, but in some cases the number of cancer cells rises more quickly.

Trial detailsLast updated 22 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2026-525656-28-00Protocol codeLP-168-US-CLL301Estimated enrolment168 patients

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