A Study Evaluating the Efficacy and Safety of Pirtobrutinib in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Loxo Oncology

Status and phase: Enrolling; Phase 2

Conditions: Small Lymphocytic Lymphoma; Chronic Lymphocytic Leukemia

Treatments: Drug: Pirtobrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06588478

2024-515689-15-01 (EU Trial (CTIS) Number)

J2N-MC-JZNX (Other Identifier)

18877

Details and patient eligibility

About

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.

Enrollment: 249 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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249 participants in 4 patient groups

Pirtobrutinib Standard Dose (Dose 1)-Part 1

Active Comparator group

Description:

Pirtobrutinib administered orally.

Treatment:

Drug: Pirtobrutinib

Pirtobrutinib Dose 2-Part 1

Experimental group

Description:

Pirtobrutinib administered orally.

Treatment:

Drug: Pirtobrutinib

Pirtobrutinib Dose 3-Part 1

Experimental group

Description:

Pirtobrutinib administered orally.

Treatment:

Drug: Pirtobrutinib

Pirtobrutinib Standard Dose-Part 2

Experimental group

Description:

Pirtobrutinib administered orally.

Treatment:

Drug: Pirtobrutinib