Study of LOXO-305 Versus Investigator's Choice (IdelaR or BR) in Patients With CLL or SLL

• ClinicalTrials.gov Identifier: NCT04666038
• Recruitment Status: Recruiting
• First Posted: December 14, 2020
• Last Update Posted: April 5, 2021
• Sponsor: Loxo Oncology, Inc.
• Information provided by (Responsible Party): Eli Lilly and Company ( Loxo Oncology, Inc. )

Tracking Information

• First Submitted Date: December 7, 2020
• First Posted Date: December 14, 2020
• Last Update Posted Date: April 5, 2021
• Actual Study Start Date: March 9, 2021
• Estimated Primary Completion Date: January 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 7, 2020)

To evaluate progression-free survival (PFS) of LOXO-305 monotherapy (Arm A) compared to investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) (Arm B) [ Time Frame: Up to approximately 36 months ]

Assessed per iwCLL 2018

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 10, 2021)

• To evaluate the effectiveness of Arm A compared to Arm B based on Overall Response Rate (ORR) [ Time Frame: Up to approximately 36 months ]
  Assessed per iwCLL 2018
• To evaluate the effectiveness of Arm A compared to Arm B based on Overall Survival (OS) [ Time Frame: Up to approximately 36 months ]
  Assessed by survival
• To evaluate the effectiveness of Arm A compared to Arm B based on Time to Next Treatment (TTNT) [ Time Frame: Up to approximately 36 months ]
  Defined as time from randomization to next systemic anticancer therapy for CLL/SLL
• Time to worsening (TTW) of CLL/SLL related symptoms [ Time Frame: Up to approximately 36 months ]
  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
• Time to worsening (TTW) of physical function [ Time Frame: Up to approximately 36 months ]
  Using the 5 physical function items identified from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) questionnaire (also known as the EORTC IL 19 questionnaire), physical function will be measured. The range of raw scores for these items could be from 0-20 with the highest score indicating worst function.

Original Secondary Outcome Measures (submitted: December 7, 2020)

• To evaluate the effectiveness of Arm A compared to Arm B based on Overall Response Rate (ORR) [ Time Frame: Up to approximately 36 months ]
  Assessed per iwCLL 2018
• To evaluate the effectiveness of Arm A compared to Arm B based on Overall Survival (OS) [ Time Frame: Up to approximately 36 months ]
  Assessed by survival
• To evaluate the effectiveness of Arm A compared to Arm B based on Time to Next Treatment (TTNT) [ Time Frame: Up to approximately 36 months ]
  Defined as time from randomization to next non-protocol-specified therapy for CLL/SLL
• Time to worsening (TTW) of CLL/SLL related symptoms [ Time Frame: Up to approximately 36 months ]
  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
• Time to worsening (TTW) of physical function [ Time Frame: Up to approximately 36 months ]
  Using the 5 physical function items identified from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) questionnaire (also known as the EORTC IL 19 questionnaire), physical function will be measured. The range of raw scores for these items could be from 0-20 with the highest score indicating worst function.

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

Descriptive Information

• Brief Title: Study of LOXO-305 Versus Investigator's Choice (IdelaR or BR) in Patients With CLL or SLL
• Official Title: A Phase 3 Open-Label, Randomized Study of LOXO-305 Versus Investigator's Choice of Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in BTK Inhibitor Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-321)
• Brief Summary: This is a study for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) who have previously received treatment with at least a BTK inhibitor. The main purpose is to compare LOXO-305 to idelalisib plus rituximab or bendamustine plus rituximab. Participation could last up to four years, and possibly longer, if the disease does not progress.
• Detailed Description: This is a Phase 3 global, randomized, open-label study comparing LOXO-305 (Arm A) to investigator's choice of either idelalisib plus rituximab or bendamustine plus rituximab (Arm B) in CLL/SLL patients who have been treated with at least a covalent BTK inhibitor (BTKi). Patients may have discontinued the prior covalent BTKi due to disease progression (PD) or intolerance. Patients who have received venetoclax are eligible for the study. Eligible patients will be randomized in 1:1 to Arm A and Arm B.
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Eligible patients will be randomized in 1:1 into Arm A or Arm B. Patients randomized to Arm B who have disease progression (PD) confirmed by independent review committee (IRC) may be eligible to crossover into Arm A.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Chronic Lymphocytic Leukemia
• Small Lymphocytic Lymphoma

Intervention

• Drug: LOXO-305
  Oral LOXO-305
  Other Name: Pirtobrutinib
• Drug: Idelalisib
  Oral
  Other Name: Zydelig
• Drug: Bendamustine
  IV
  Other Name: Treanda, Treakisym, Ribomustin, Levact
• Drug: Rituximab
  IV
  Other Name: Rituxan, MabThera, Truxima

Study Arms

• Experimental: Arm A (LOXO-305)
  Orally
  Intervention: Drug: LOXO-305
• Active Comparator: Arm B (Idelalisib plus rituximab [IdelaR] or bendamustine plus rituximab [BR])
  Investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR).
  Interventions:

  • Drug: Idelalisib
  • Drug: Bendamustine
  • Drug: Rituximab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 7, 2020): 250
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2024
• Estimated Primary Completion Date: January 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Confirmed diagnosis of CLL/SLL requiring therapy as defined by iwCLL 2018 criteria
• Previously treated with a covalent BTK inhibitor
• Eastern Cooperative Oncology Group (ECOG) 0-2
• Absolute neutrophil count ≥ 0.75 × 109/L without granulocyte-colony stimulating factor support
• Hemoglobin ≥ 8 g/dL not requiring transfusion support or growth factors within 14 days of Cycle 1 Day 1
• Platelets ≥ 50 × 109/L not requiring transfusion support or growth factors within 14 days of C1D1. If an investigator has chosen bendamustine/rituximab as the Arm B treatment, platelets must be ≥ (75 × 109/L).
• AST and ALT ≤ 3.0 x upper limit of normal (ULN).
• Total bilirubin ≤ 1.5 x ULN.
• Estimated creatinine clearance of ≥ 30 mL/min.

Exclusion Criteria:

• Known or suspected Richter's transformation at any time preceding enrollment.
• Known or suspected history of central nervous system (CNS) involvement by CLL/SLL
• Ongoing drug-induced liver injury
• Active uncontrolled auto-immune cytopenia
• Significant cardiovascular disease
• History of allogeneic or stem cell transplantation (SCT) or chimeric antigen receptor-modified T cells (CAR-T) therapy within the past 60 days
• Active hepatitis B or hepatitis C
• Known active cytomegalovirus (CMV) infection.
• Active uncontrolled systemic bacterial, viral, fungal or parasitic infection.
• Known Human Immunodeficiency Virus (HIV) infection, regardless of CD4 count.
• Clinically significant active malabsorption syndrome or inflammatory bowel disease
• Prior exposure to non-covalent (reversible) BTK inhibitor.
• Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist.
• Current treatment with strong cytochrome P450 (CYP) 3A4 (CYP3A4) inhibitors or inducers and/or strong P-glycoprotein (P-gp) inhibitors
• Vaccination with a live vaccine within 28 days prior to randomization

• Patients with the following hypersensitivity:

  1. Known hypersensitivity, including anaphylaxis, to any component or excipient of LOXO-305, idelalisib, and bendamustine
  2. Prior significant hypersensitivity to rituximab

Sex/Gender

• Sexes Eligible for Study: All

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

Contacts

Contact: Patient Advocacy; 1-855-LOXO-305; clinicaltrials@loxooncology.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04666038
• Other Study ID Numbers: LOXO-BTK-20020
• 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: Not Provided
• Responsible Party: Eli Lilly and Company ( Loxo Oncology, Inc. )
• Study Sponsor: Loxo Oncology, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Safi Shahda, MD; Loxo Oncology

• PRS Account: Eli Lilly and Company
• Verification Date: April 2021