The main purpose of Part 1 of this study is to assess the efficacy and safety of 3 dose levels of Pirtobrutinib in participants with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), who have received 1-3 lines of treatment including a covalent Bruton tyrosine kinase (BTK) inhibitor. The purpose of Part 2 of this study is to evaluate pirtobrutinib monotherapy in participants with treatment-naïve CLL/SLL with 17p deletions. Participation in Part 1 is expected to last approximately 3 years. Participation in Part 2 is expected to last up to 2 years.

Inclusion Criteria:

• Have confirmed diagnosis of CLL/SLL as defined by iwCLL 2018 criteria.

• Part 1: Have received prior CLL/SLL treatment

• Have received at least 1, but not more than 3 lines of prior treatment for CLL/SLL

• Have received a covalent BTK inhibitor

• Part 2: Have received no prior treatment for CLL/SLL

  • Part 1 - Known 17p deletion status (positive or negative)
  • Part 2 - Must have 17p deletion (positive)

• Have a requirement for therapy consistent with iwCLL 2018 criteria for initiation of therapy

• Capable of swallowing oral study medication.

• Have an Eastern Cooperative Oncology Group Performance Status (ECOG) score of 0 to 2.

Exclusion Criteria:

• Have received prior treatment with a BTK degrader or a noncovalent BTK inhibitor

• Have a history of greater than or equal to (>=) Grade 3 bleeding due to treatment with a BTK inhibitor

• Have known or suspected Richter's transformation

• Have known or suspected history of central nervous system involvement by CLL/SLL

• Previous or concurrent cancer distinct from CLL/SLL within 3 years before randomization. Exceptions may occur with documented sponsor approval. Examples include:

  • nonmelanoma skin cancer or lentigo malignant melanoma
  • cervical carcinoma in situ
  • localized prostate cancer undergoing active surveillance, and
  • localized (for example, lymph node negative) breast cancer with no evidence of active disease present for more than 3 years. Individual may be receiving adjuvant hormonal therapy

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Part 2 is non-randomized