A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) (BRUIN-CLL-314)

• ClinicalTrials.gov Identifier: NCT05254743
• Recruitment Status: Recruiting
• First Posted: February 24, 2022
• Last Update Posted: May 13, 2024
• Sponsor: Loxo Oncology, Inc.
• Collaborator: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company ( Loxo Oncology, Inc. )

Tracking Information

• First Submitted Date: February 15, 2022
• First Posted Date: February 24, 2022
• Last Update Posted Date: May 13, 2024
• Actual Study Start Date: July 22, 2022
• Estimated Primary Completion Date: February 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 12, 2023)

Percentage of Participants Achieving Complete Response (CR), Complete Remission with Incomplete Hematologic Recovery (Cri), Nodular Partial Remission (nPR) or Partial Response (PR): Overall Response Rate (ORR) [ Time Frame: Baseline to best overall response at or before the initiation of subsequent anti-cancer therapy (if any) (approximately 3 years and 5 months) ]

ORR as assessed by independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria

Original Primary Outcome Measures (submitted: February 15, 2022)

Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Overall Response Rate (ORR) [ Time Frame: Baseline to disease progression (up to approximately 3 years and 5 months) ]

ORR as assessed by independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria

Current Secondary Outcome Measures (submitted: April 12, 2023)

• Event-Free Survival (EFS) [ Time Frame: Randomization to first occurrence of treatment discontinuation due to adverse event/toxicity, treatment-emergent atrial fibrillation or atrial flutter of any grade, progressive disease (PD) or death (approximately 4 years) ]
  EFS by IRC per iwCLL 2018 criteria
• Progression-Free Survival (PFS) [ Time Frame: Randomization to PD (per iwCLL 2018 criteria) or death from any cause (approximately 5 years 8 months) ]
  PFS by IRC per iwCLL 2018 criteria
• Duration of Response (DOR) [ Time Frame: Time from the date of the first documented response of CR, CRi, nPR or PR to the earlier of documentation of definitive PD (per iwCLL 2018 criteria) or death from any cause (approximately 2 years) ]
  DOR
• Overall Survival (OS) [ Time Frame: Randomization to death from any cause (approximately 6 years) ]
  OS
• Time to Next Treatment (TTNT) [ Time Frame: Randomization to initiation of the next systemic anticancer therapy for CLL/SLL or death from any cause, whichever occurs first (approximately 6 years) ]
  TTNT
• Time to Worsening (TTW) of CLL/SLL Related Symptoms [ Time Frame: Randomization to time to worsening symptoms (approximately 6 years) ]
  Using symptom questions identified from the EORTC item library. The range of raw scores for these items could be from 0 to 52 with highest score being worse symptoms.

Original Secondary Outcome Measures (submitted: February 15, 2022)

• Event-Free Survival (EFS) [ Time Frame: Randomization until treatment discontinuation due to adverse event (AE)/toxicity, atrial fibrillation or atrial flutter of any grade, or progressive disease (PD) (by IRC per iwCLL 2018 criteria) or death (up to approximately 4 years) ]
  EFS
• Progression-Free Survival (PFS) [ Time Frame: Randomization until PD (per iwCLL 2018 criteria) or death from any cause (up to approximately 5 years 8 months) ]
  PFS
• Time to worsening (TTW) of CLL/SLL related symptoms [ Time Frame: Randomization to time to worsening symptoms (up to approximately 6 years) ]
  Using symptom questions identified from the EORTC item library. The range of raw scores for these items could be from 0 to 52 with highest score being worse symptoms.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
• Official Title: A Phase 3 Open-Label, Randomized Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN-CLL-314)
• Brief Summary: The purpose of this study is to compare the efficacy and safety of pirtobruitinib (LOXO-305) to ibrutinib in participants with CLL/SLL. Participants may or may not have already had treatment for their cancer. Participation could last up to six years.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Chronic Lymphocytic Leukemia
• Leukemia, Lymphocytic
• Leukemia, B-cell
• Small Lymphocytic Lymphoma

Intervention

• Drug: Pirtobrutinib
  Administered orally.
  Other Names:

  • LOXO-305
  • LY3527727
• Drug: Ibrutinib
  Administered orally.

Study Arms

• Experimental: Pirtobrutinib
  Administered orally.
  Intervention: Drug: Pirtobrutinib
• Active Comparator: Ibrutinib
  Administered orally.
  Intervention: Drug: Ibrutinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 15, 2022): 650
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2028
• Estimated Primary Completion Date: February 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Confirmed diagnosis of CLL/SLL requiring therapy per iwCLL 2018 criteria
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

• Adequate organ function

  • Platelets greater than or equal to (≥)50 x 10⁹/liter (L) or ≥30 x 10⁹/L in participants with documented bone marrow involvement considered to impair hematopoiesis,
  • Hemoglobin ≥8 grams/deciliter (g/dL) or ≥6 g/dL in participants with documented bone marrow involvement considered to impair hematopoiesis
  • Absolute neutrophil count ≥0.75 x 10⁹/L or ≥0.50 × 10⁹/L in participants with documented bone marrow involvement considered to impair hematopoiesis
  • Kidney function: Estimated creatinine clearance ≥30 milliliters per minute (mL/min)

Exclusion Criteria:

• Known or suspected Richter's transformation to diffuse large B-cell lymphoma (DLBCL), prolymphocytic leukemia, or Hodgkin's lymphoma at any time preceding enrollment
• Known or suspected central nervous system (CNS) involvement
• A significant history of renal, neurologic, psychiatric, endocrine, metabolic or immunologic disease
• Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP])
• Significant cardiovascular disease including ejection fraction < 40% and any grade ongoing atrial fibrillation or atrial flutter
• Hepatitis B or hepatitis C testing indicating active/ongoing infection, based on Screening laboratory tests
• Active cytomegalovirus (CMV) infection
• Active uncontrolled systemic bacterial, viral, or fungal infection
• Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count
• Clinically significant active malabsorption syndrome or other condition likely to affect GI absorption of the oral-administered study treatments
• Ongoing inflammatory bowel disease
• Prior exposure to BTK inhibitor (covalent or noncovalent)
• Concurrent use of investigational agent or anticancer therapy except hormonal therapy
• Participants requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist
• Use of ≥ 20 mg prednisone daily or equivalent dose of steroid at the time of first dose of study drug
• Vaccination with a live vaccine within 28 days prior to randomization
• Participants receiving chronic therapy with a strong cytochrome P450 (CYP)3A inhibitor (except posaconazole and voriconazole) which cannot be stopped within 3-5 half lives of the CYP3A inhibitor therapy prior to start of study drug treatment
• Participants with known hypersensitivity, including anaphylaxis, to any component or excipient of pirtobrutinib or ibrutinib

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or; 1-317-615-4559; ClinicalTrials.gov@lilly.com

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Czechia, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, New Zealand, Poland, Spain, Taiwan, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05254743
• Other Study ID Numbers: 18281; J2N-OX-JZNU ( Other Identifier: Eli Lilly and Company ); LOXO-BTK-20030 ( Other Identifier: Loxo Oncology, Inc. ); 2021-003206-41 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: http://vivli.org/

• Current Responsible Party: Eli Lilly and Company ( Loxo Oncology, Inc. )
• Original Responsible Party: Same as current
• Current Study Sponsor: Loxo Oncology, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: May 2024