A Trial of Pirtobrutinib (LOXO-305) Plus Venetoclax and R... | NCT04965493

Studies
A Trial of Pirtobrutinib (LOXO-305) Plus Venetoclax and Rituximab (PVR) Versus Venetoclax and Rituximab (VR) in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

NCT04965493

Sponsor

Loxo Oncology, Inc.

Status

Active, not recruiting

Last Update Posted

Jan 29, 2026Actual

Enrollment

600Estimated

Phase

Phase 3

Conditions

Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma

Interventions

Pirtobrutinib
Venetoclax
Rituximab

Countries

United States
Australia
Belgium
Canada
China
Czechia
Denmark
France
Germany
Hungary
Ireland
Israel
Italy
Japan
Norway
Poland
Singapore
South Korea
Spain
Sweden
Switzerland
Taiwan
United Kingdom

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

ID	Type	Description	Link
J2N-OX-JZNO	Other Identifier	Eli Lilly and Company
LOXO-BTK-20022	Other Identifier	Eli Lilly and Company

Status Module

Record Verification Date

Jan 2026

Overall Recruitment Status or Expanded Access Status

Active, not recruiting

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

Sep 20, 2021Actual

Primary Completion Date

Oct 2026Estimated

Completion Date

Oct 2027Estimated

First Submitted Date

Jul 15, 2021

First Submission Date that Met QC Criteria

Jul 15, 2021

First Posted Date

Jul 16, 2021Actual

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Jan 27, 2026

Last Update Posted Date

Jan 29, 2026Actual

Name	Class
Eli Lilly and Company	INDUSTRY

Label	Type	Description	Intervention Names
Arm A (PVR)	Experimental	Fixed duration pirtobrutinib in combination with venetoclax and rituximab	Drug: Pirtobrutinib Drug: Venetoclax Drug: Rituximab
Arm B (VR)	Active Comparator	Venetoclax with rituximab	Drug: Venetoclax Drug: Rituximab

Name	Type	Description	Arm Group Labels	Other Names
Pirtobrutinib	Drug	Oral	Arm A (PVR)	LOXO-305 LY3527727

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
To evaluate progression-free survival (PFS) of pirtobrutinib plus venetoclax and rituximab (Arm A) compared to venetoclax and rituximab (Arm B)	Assessed by blinded independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018	Up to approximately 5 years

Secondary Outcomes

Measure	Description	Time Frame
To evaluate the efficacy of Arm A compared to Arm B: Progression-free survival (PFS)	Assessments of efficacy include PFS, assessed by investigator	Up to approximately 5 years
To evaluate the efficacy of Arm A compared to Arm B: Overall survival (OS)

Other Outcomes

Not provided

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Confirmed diagnosis of CLL/SLL requiring therapy per iwCLL 2018 criteria
Previous treatment with at least one line of therapy that may include a covalent Bruton's tyrosine kinase (BTK) inhibitor
Platelets greater than or equal to (≥)50 x 10⁹/liter (L), hemoglobin ≥8 grams/deciliter (g/dL) and absolute neutrophil count ≥1.0 x 10⁹/L
Adequate organ function
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
Estimated creatinine clearance ≥30 milliliters per minute (mL/min)

Exclusion Criteria:

Known or suspected Richter's transformation at any time preceding enrollment
Prior therapy with a 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
Prior therapy with venetoclax
Central nervous system (CNS) involvement
Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection
Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count
Allogeneic stem cell transplantation (SCT) or chimeric antigen receptor (CAR)-T within 60 days
Active hepatitis B or hepatitis C
Known active cytomegalovirus (CMV) infection
Uncontrolled immune thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia (AIHA)
Significant cardiovascular disease
Vaccination with a live vaccine within 28 days prior to randomization
Patients with the following hypersensitivity:
- Known hypersensitivity to any component or excipient of pirtobrutinib and venetoclax
- Prior significant hypersensitivity to rituximab
- Known allergy to allopurinol and inability to take uric acid lowering agent

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

Not provided

Standard Ages

AdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

ID	Term
D015451	Leukemia, Lymphocytic, Chronic, B-Cell
D006402	Hematologic Diseases
D008228	Lymphoma, Non-Hodgkin
D016393	Lymphoma, B-Cell

ID	Term
D015448	Leukemia, B-Cell
D007945	Leukemia, Lymphoid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006425	Hemic and Lymphatic Diseases
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D008223	Lymphoma

ID	Term
D058846	Antibodies, Monoclonal, Murine-Derived
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins