Pirtobrutinib

Pirtobrutinib is a small molecule, noncovalent inhibitor of BTK. BTK is a signaling protein of the B-cell antigen receptor (BCR) and cytokine receptor pathways.

• JAYPIRCA ® is a kinase inhibitor 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. ( 1.1 ).ICD-10: C85.90

• None. None ( 4 ).contraindicated

Recommended dosage: 200 mg orally once daily; swallow whole with water, with or without food. Do not cut, crush, or chew tablets. ( 2.1 ) Manage toxicity using treatment interruption, dosage reduction, or discontinuation. ( 2.2 ) Reduce dose in patients with severe renal impairment. ( 2.3 , 8.6 ) 2.1 Recommended Dosage The recommended dosage of JAYPIRCA is 200 mg orally once daily until disease progression or unacceptable toxicity. Advise patients of the following: Swallow tablets whole with water. Do not cut, crush, or chew tablets. Take JAYPIRCA at the same time each day. JAYPIRCA may be taken with or without food. If a dose of JAYPIRCA is missed by more than 12 hours, do not make up the dose and take the next dose as scheduled. 2.2 Dosage Modifications for Adverse Reactions Recommended dosage modifications of JAYPIRCA for adverse reactions are presented in Table 1 [see Warnings and Precautions ( 5.1 , 5.2 , 5.3 , and 5.4 )] . Table 1: Recommended Dosage Modification of JAYPIRCA for Adverse Reactions Dose modification is not recommended for asymptomatic lymphocytosis. Asymptomatic lipase increase may not necessarily warrant dose modification. a Evaluate the benefit-risk before resuming treatment at the same dose for a Grade 4 non-hematological toxicity.

Infections: Monitor for signs and symptoms of infection, evaluate promptly, and treat. ( 5.1 ) Hemorrhage: Monitor for bleeding and manage appropriately. ( 5.2 ) Cytopenias: Monitor complete blood counts during treatment. ( 5.3 ) Cardiac Arrythmias: Monitor for symptoms of arrhythmias and manage appropriately. ( 5.4 ) Second Primary Malignancies: Other malignancies have developed, including skin cancers and other carcinomas. Monitor and advise patients to use sun protection. ( 5.5 ) Hepatotoxicity, Including Drug-Induced Liver Injury: Monitor hepatic function throughout treatment. ( 5.6 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception. ( 5.7 , 8.1 , 8.3 ) 5.1 Infections Fatal and serious infections (including bacterial, viral, or fungal infections) and opportunistic infections have occurred in patients treated with JAYPIRCA. Across clinical trials, Grade 3 or higher infections occurred in 25% of 704 patients, most commonly pneumonia (20%), with fatal infections occurring in 5% of patients. Sepsis occurred in 6% of patients and febrile neutropenia in 3.8%. In patients with CLL/SLL, Grade 3 or higher infections occurred in 32% of patients, with fatal infections occurring in 8%. Opportunistic infections after treatment with JAYPIRCA have included, but are not limited to, Pneumocystis jirovecii pneumonia and fungal infection [see Adverse Reactions ( 6.1 )] .

The following clinically significant adverse reactions are described elsewhere in the labeling: Infections [see Warnings and Precautions ( 5.1 )] Hemorrhage [see Warnings and Precautions ( 5.2 )] Cytopenias [see Warnings and Precautions ( 5.3 )] Atrial Fibrillation and Atrial Flutter [see Warnings and Precautions ( 5.4 )] Second Primary Malignancies [see Warnings and Precautions ( 5.5 )] Hepatotoxicity, including DILI [see Warnings and Precautions ( 5.6 )] Most common adverse reactions (≥ 30%), including laboratory abnormalities, are fatigue, neutrophil count decreased, platelet count decreased, hemoglobin decreased, leukocytes decreased, lymphocyte count decreased and calcium decreased. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be compared to rates in the clinical trials of another drug and may not reflect the rates observed in the general patient population. The data in the WARNINGS AND PRECAUTIONS reflect exposure to JAYPIRCA as a single-agent, administered at 200 mg once daily in 704 patients with hematologic malignancies in the BRUIN and the BRUIN-CLL-321 studies. Among these 704 patients, the median duration of exposure was 12 months; 65% were exposed for at least 6 months and 50% were exposed for at least one year.

Lactation: Advise not to breastfeed ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings from animal studies, JAYPIRCA can cause fetal harm when administered to a pregnant woman. There are no available data on JAYPIRCA use in pregnant women to evaluate for a drug-associated risk. In an animal reproduction study, administration of pirtobrutinib to pregnant rats during organogenesis resulted in adverse developmental outcomes, including structural abnormalities, altered fetal growth, and embryo-fetal mortality, at maternal exposures approximately 3-times those in patients at the recommended daily dose of 200 mg (see Data). Advise pregnant women of the potential risk to a fetus. The background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Data Animal Data In an embryo-fetal development study in rats, pregnant animals were administered oral doses of pirtobrutinib at up to 500 mg/kg twice daily during the period of organogenesis. Doses ≥ 375 mg/kg twice daily caused decreased fetal body weights and increased incidence of malformations and variations in the urinary tract (including absent or abnormal ureters and kidneys), reproductive tract (malpositioned ovaries and misshapen uterus), and bone (misshapen sternebrae). At 500 mg/kg twice daily, total resorption was observed.

Metabolism

The pharmacokinetics of pirtobrutinib were characterized in healthy subjects and in patients with cancer. Pirtobrutinib exposure (AUC) and C max increases proportionally following single oral doses ranging from 300 mg to 800 mg (1.5 to 4 times the approved recommended dosage) and once daily doses ranging from 25 – 300 mg (0.125 to 1.5 times the recommended dosage).

• Jan 27, 2023NDANDA216059Loxo Oncol

1. 1Death9614%
2. 2Malignant Neoplasm Progression699.9%
3. 3Pneumonia588.3%
4. 4Disease Progression466.6%
5. 5Off Label Use385.4%
6. 6Chronic Lymphocytic Leukaemia365.2%
7. 7Anaemia324.6%
8. 8Pancytopenia304.3%
9. 9Lymphadenopathy294.2%
10. 10Drug Ineffective284.0%
11. 11Splenomegaly243.4%
12. 12White Blood Cell Count Increased243.4%
13. 13Cytokine Release Syndrome233.3%
14. 14General Physical Health Deterioration233.3%
15. 15Covid-19213.0%

The 10 most recently updated of 71 ClinicalTrials.gov registrations naming Pirtobrutinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Adding Pirtobrutinib to the Usual Treatment for People With Newly Diagnosed Richter Transformation, The PIRAMID Trial
  Not yet recruiting · Phase 3 · Interventional · 102 enrolled · SWOG Cancer Research Network
  NCT07220187updated 2026-06-11
• A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
  Recruiting · Phase 3 · Interventional · 737 enrolled · Loxo Oncology, Inc.
  NCT05254743updated 2026-06-09
• Pirtobrutinib and Mosunetuzumab for the Treatment of Relapsed/Refractory Grades 1-3A Follicular Lymphoma, PROMOTE-FL Trial
  Recruiting · Phase 2 · Interventional · 22 enrolled · University of Washington
  NCT06948786updated 2026-06-04
• Immune Profiling of CLL/SLL Treated With First-Line Pirtobrutinib
  Recruiting · Early phase 1 · Interventional · 30 enrolled · National Heart, Lung, and Blood Institute (NHLBI)
  NCT07428707updated 2026-06-04
• A Study of Pirtobrutinib, Venetoclax, and Rituximab in People With Waldenström's Macroglobulinemia (WM)/Lymphoplasmacytic Lymphoma (LPL)
  Recruiting · Phase 2 · Interventional · 40 enrolled · Memorial Sloan Kettering Cancer Center
  NCT07231952updated 2026-06-03
• A Study to Evaluate the Safety and Efficacy of BGB-16673 Compared to Pirtobrutinib in Adults With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
  Recruiting · Phase 3 · Interventional · 500 enrolled · BeOne Medicines
  NCT06973187updated 2026-06-03
• Fixed Duration Treatment With Combined Pirtobrutinib and Short Course Immuno-chemotherapy in Fit Patients With Previously Untreated Symptomatic Chronic Lymphocytic Leukemia (CLL).
  Not yet recruiting · Phase 2 · Interventional · 82 enrolled · French Innovative Leukemia Organisation
  NCT07624799updated 2026-06-03
• Pirtobrutinib Maintenance After CAR-T Therapy in Relapsed or Refractory B-Cell Lymphoma
  Not yet recruiting · Phase 2 · Interventional · 20 enrolled · Sun Yat-sen University
  NCT07622784updated 2026-06-03
• A Multicenter, Prospective Clinical Trial With a Concurrent Control Evaluating Methotrexate Combined With Rituximab,Sintilimab and Pirtobrutinib vs. Investigator-Selected Standard of Care in Treatment-Naive PCNSL
  Recruiting · Phase 2 · Interventional · 77 enrolled · Tongji Hospital
  NCT07350850updated 2026-06-02
• A Study to Evaluate Adverse Events and Change in Disease Activity of Subcutaneous (SC) Epcoritamab in Combination With Oral and Intravenous Anti-Neoplastic Agents in Adult Participants With Non-Hodgkin Lymphoma
  Recruiting · Phase 2 · Interventional · 496 enrolled · Genmab
  NCT05283720updated 2026-06-02

Frequently asked questions

How does Pirtobrutinib work?

Pirtobrutinib is a small molecule, noncovalent inhibitor of BTK. BTK is a signaling protein of the B-cell antigen receptor (BCR) and cytokine receptor pathways.

What is Pirtobrutinib used for?

According to FDA labeling, Pirtobrutinib carries indications including: JAYPIRCA ® is a kinase inhibitor 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. ( 1.1 ).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Pirtobrutinib?

Pirtobrutinib is classified as Bruton's tyrosine kinase (BTK) inhibitors, Kinase Inhibitor, Breast Cancer Resistance Protein Inhibitors, Bruton's Tyrosine Kinase Inhibitors, Cytochrome P450 2C19 Inhibitors, Cytochrome P450 2C8 Inhibitors, Cytochrome P450 3A Inhibitors, P-Glycoprotein Inhibitors.

What are the brand names for Pirtobrutinib?

Pirtobrutinib is marketed under brand names including Jaypirca.

What are the contraindications for Pirtobrutinib?

Pirtobrutinib labeling lists contraindications including: None. None ( 4 ).. Always consult the full prescribing information and a clinician.