Pirtobrutinib

Generic Name: Pirtobrutinib

Brand Names: Jaypirca

Drug Type: Small Molecule

Chemical Formula: C_₂₂H_₂₁F_₄N_₅O_₃

CAS Number: 2101700-15-4

Unique Ingredient Identifier: JNA39I7ZVB

Background: Pirtobrutinib is a small molecule and a highly selective non-covalent inhibitor of Bruton’s tyrosine kinase (BTK). Its high selectivity has been associated with lower discontinuation rates due to adverse events and a lower incidence of atrial fibrillation. Unlike BTK covalent inhibitors, such as ibrutinib, that bind to the cysteine 481 (Cys481) amino acid within the active site of BTK, the inhibitory activity of pirtobrutinib is maintained even in the presence of Cys481 mutations. Although the mechanisms of resistance to covalent BTK inhibitors have not been fully elucidated, it appears that the presence of Cys481 mutations is the most common reason for resistance to covalent BTK inhibitors. However, other mutations may confer resistance to non-covalent BTK inhibitors such as pirtobrutinib.

In January 2023, the use of pirtobrutinib for the treatment of relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy was approved under the FDA's Accelerated Approval pathway.

Indication: Pirtobrutinib is indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.

Associated Conditions: Refractory Mantle Cell Lymphoma, Relapsed Mantle Cell Lymphoma

Clinical Trials

Study of Oral LOXO-338 in Patients With Advanced Blood Cancers

Phase 1

Active, not recruiting

Conditions: Multiple Myeloma
Waldenstrom Macroglobulinemia
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Non-Hodgkin
Lymphoma, Mantle-Cell
Lymphoma, B-cell Marginal Zone
B-cell Lymphoma

Interventions: Drug: LOXO-338
Drug: Pirtobrutinib

First Posted Date: 2021-08-27

Last Posted Date: 2025-04-18

Lead Sponsor: Eli Lilly and Company

Target Recruit Count: 316

Registration Number: NCT05024045

Locations: 🇺🇸
The University of Arizona Cancer Center, Tucson, Arizona, United States
🇺🇸
City of Hope National Medical Center, Duarte, California, United States
🇺🇸
Mayo Clinic in Florida, Jacksonville, Florida, United States

and more 20 locations

A Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab (BR) in Untreated Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

Phase 3

Active, not recruiting

Conditions: Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma

Interventions: Drug: Pirtobrutinib
Drug: Bendamustine
Drug: Rituximab

First Posted Date: 2021-08-27

Last Posted Date: 2025-04-25

Lead Sponsor: Loxo Oncology, Inc.

Target Recruit Count: 250

Registration Number: NCT05023980

Locations: 🇨🇳
Hunan Cancer Hospital, Changsha, Hunan, China
🇧🇷
Hospital de Clinicas de Porto Alegre, Porto Alegre, Rio Grande Do Sul, Brazil
🇧🇷
Centro Gaucho Integrado - Mae de Deus Center, Porto Alegre, Rio Grande Do Sul, Brazil

and more 105 locations

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)

Phase 3

Active, not recruiting

Conditions: Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma

Interventions: Drug: Pirtobrutinib
Drug: Venetoclax
Drug: Rituximab

First Posted Date: 2021-07-16

Last Posted Date: 2025-05-21

Lead Sponsor: Loxo Oncology, Inc.

Target Recruit Count: 600

Registration Number: NCT04965493

Locations: 🇮🇹
IRCCS - AOU di Bologna, Bologna, Italy
🇮🇹
Ospedale Santa Croce e Carle, Cuneo, Italy
🇮🇹
A.O.U. di Modena, Modena, Italy

and more 174 locations

A Study of LOXO-305 in Chinese Participants With Blood Cancer (Including Lymphoma and Chronic Leukemia)

Phase 2

Active, not recruiting

Conditions: Leukemia, Lymphoid
Lymphoma, Non-Hodgkin
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Leukemia, Lymphocytic, Chronic, B-Cell

Interventions: Drug: LOXO-305

First Posted Date: 2021-04-19

Last Posted Date: 2025-04-20

Lead Sponsor: Eli Lilly and Company

Target Recruit Count: 87

Registration Number: NCT04849416

Locations: 🇨🇳
Beijing Cancer hospital, Beijing, Beijing, China
🇨🇳
Hainan General Hospital, Haikou, Hainan, China
🇨🇳
Xingtai People's Hospital, Xingtai, Hebei, China

and more 19 locations

Study of LOXO-305 (Pirtobrutinib) Versus Investigator's Choice (Idelalisib Plus Rituximab or Bendamustine Plus Rituximab) in Patients With Previously Treated Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

Phase 3

Active, not recruiting

Conditions: Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma

Interventions: Drug: Pirtobrutinib
Drug: Idelalisib
Drug: Bendamustine
Drug: Rituximab

First Posted Date: 2020-12-14

Last Posted Date: 2025-04-20

Lead Sponsor: Loxo Oncology, Inc.

Target Recruit Count: 238

Registration Number: NCT04666038

Locations: 🇨🇦
Princess Margaret Hospital (Ontario), Toronto, Ontario, Canada
🇺🇸
Community Health Network, Indianapolis, Indiana, United States
🇨🇳
Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China

and more 229 locations

Study of BTK Inhibitor LOXO-305 Versus Approved BTK Inhibitor Drugs in Patients With Mantle Cell Lymphoma (MCL)

Phase 3

Recruiting

Conditions: Lymphoma, Mantle-Cell

Interventions: Drug: Ibrutinib
Drug: Pirtobrutinib
Drug: Acalabrutinib
Drug: Zanubrutinib

First Posted Date: 2020-12-10

Last Posted Date: 2025-05-21

Lead Sponsor: Loxo Oncology, Inc.

Target Recruit Count: 500

Registration Number: NCT04662255

Locations: 🇺🇸
Alaska Oncology and Hematology, LLC, Anchorage, Alaska, United States
🇺🇸
Arizona Oncology Associates, P.C. - HOPE, Phoenix, Arizona, United States
🇺🇸
UCLA Medical Center, Los Angeles, California, United States

and more 186 locations

Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome

Phase 1

Recruiting

Conditions: Relapsed/Refractory Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Richter's Syndrome
Treatment-naïve High Risk Chronic Lymphocytic Leukemia

Interventions: Biological: Epcoritamab
Drug: Venetoclax
Drug: Lenalidomide
Drug: rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone
Drug: Pirtobrutinib

First Posted Date: 2020-11-10

Last Posted Date: 2025-05-06

Lead Sponsor: Genmab

Target Recruit Count: 424

Registration Number: NCT04623541

Locations: 🇫🇷
CHU de Montpellier Hôpital Saint Eloi, Montpellier, Cedex 5, France
🇺🇸
O'Neal Comprehensive Cancer Center at University of Alabama at Birmingham, Birmingham, Alabama, United States
🇺🇸
University of California Davis Medical Center Sacramento, California City, California, United States

and more 74 locations

A Study of Oral LOXO-305 in Patients With Previously Treated CLL/SLL or NHL

Phase 1

Active, not recruiting

Conditions: Waldenstrom Macroglobulinemia
Mantle Cell Lymphoma
Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia
B-cell Lymphoma
Marginal Zone Lymphoma

Interventions: Drug: Pirtobrutinib
Drug: Venetoclax
Drug: Rituximab

First Posted Date: 2018-11-14

Last Posted Date: 2025-04-06

Lead Sponsor: Loxo Oncology, Inc.

Target Recruit Count: 860

Registration Number: NCT03740529

Locations: 🇺🇸
University of Pennsylvania Hospital, Philadelphia, Pennsylvania, United States
🇺🇸
Ohio State University Hospital, Columbus, Ohio, United States
🇺🇸
Cleveland Clinic Foundation, Cleveland, Ohio, United States

and more 53 locations

Drug Development Updates

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