Study Comparing Pirtobrutinib (LOXO-305) and Ibrutinib for Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)

Inclusion Criteria

• Have a confirmed diagnosis of CLL or SLL that requires treatment.
• For Part 1, must know the status of a genetic marker called 17p deletion.
• For Part 2, must have a 17p deletion as shown by specific testing.
• Be in good general health with an ECOG performance status of 0 to 2, meaning fully active or with some restrictions but able to carry out light work.
• Have adequate organ function, including:
  • Platelet count of at least 50,000 per microliter, or 30,000 if bone marrow is affected.
  • Hemoglobin level of at least 8 grams per deciliter, or 6 if bone marrow is affected.
  • Neutrophil count of at least 750 per microliter, or 500 if bone marrow is affected.
  • Kidney function with creatinine clearance of at least 30 milliliters per minute.

Exclusion Criteria

• Have a history or suspicion of certain other types of lymphoma or leukemia.
• Have cancer that has spread to the brain or spinal cord.
• Have significant health issues affecting the kidneys, brain, mental health, hormones, metabolism, or immune system.
• Have uncontrolled autoimmune blood disorders.
• Have serious heart conditions, including certain heart rhythms or low heart function.
• Have active hepatitis B or C, or cytomegalovirus (CMV) infection.
• Have active, uncontrolled infections.
• Have HIV infection.
• Have digestive issues that affect absorption of oral medications.
• Have inflammatory bowel disease.
• For Part 1, have had previous treatment for CLL/SLL, except for certain drugs.
• For Part 2, must not have had any previous treatment for CLL/SLL.
• Be using other experimental drugs or cancer treatments, except hormone therapy.
• Require certain blood thinners like warfarin.
• Be taking more than 20 mg of prednisone daily or equivalent.
• Have received a live vaccine within 28 days before starting the study.
• Be on certain strong medications that affect drug metabolism and cannot be stopped before starting the study.
• Have known allergies to components of pirtobrutinib or ibrutinib.