Pirtobrutinib

Pirtobrutinib (Jaypirca) is a targeted cancer therapy used to treat chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL) in specific patients.

Pirtobrutinib is a BTK inhibitor that blocks BTK, a key enzyme that helps B-cell cancers survive and grow. By blocking BTK, Jaypirca helps to inhibit or prevent cancer cells from surviving and multiplying, which can slow the spread of MCL and CLL.

Jaypirca tablets are taken once daily, swallowed whole with water, with or without food. Do not cut, crush, or chew tablets.

Pirtobrutinib is used for the treatment of adult patients with:

• Chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) that is:
• Relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of treatment, including a BTK inhibitor. This indication is approved under accelerated approval based on the response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Pirtobrutinib is a BTK inhibitor.

Pirtobrutinib's mechanism of action (MOA) is to selectively block Bruton’s tyrosine kinase (BTK), a key driver of B-cell signaling, resulting in slowing of B-cell growth and the death of malignant B cells.

Because pirtobrutinib is a highly selective non-covalent (reversible) BTK inhibitor, it can target the BTK pathway in patients with relapsed or refractory disease, even after prior covalent BTK inhibitors have failed.

Pirtobrutinib (brand name Jaypirca) FDA approval was granted for mantle cell lymphoma (accelerated approval) on January 27, 2023, based on positive results from the BRUIN Phase 1/2 trial (NCT03740529). The original FDA approval has been extended to include relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) in certain patients.

The BRUIN Phase 1/2 trial demonstrated:

• 50% of Jaypirca patients experienced an improvement in their MCL
• For 35% of patients who responded, the improvement lasted at least 6 months
• For 15% of patients who responded, the improvement lasted at least 12 months.

Pirtobrutinib instructions

Take pirtobrutinib tablets 1 time each day at about the same time each day. Tablets can be taken with or without food. Tablets should be swallowed whole with water. Do not cut, crush, or chew the tablets.

General Information

Take pirtobrutinib tablets exactly as your healthcare provider tells you. Do not change your dose or stop treatment unless your healthcare provider tells you to do so.

You will need to have blood tests often.

Using this medicine may increase your risk of developing cancer. Ask your doctor about your individual risk.

Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Infections. Serious and deadly infections caused by bacteria, viruses, or fungi have occurred with pirtobrutinib, 24% were Grade 3 or higher; opportunistic infections such as those caused by Pneumocystis jirovecci pneumonia also occurred. Consider prophylaxis, such as vaccinations and antibiotics in those at increased risk.

Bleeding. Serious and fatal bleeding events (hemorrhage) have also occurred with pirtobrutinib. Monitor for any signs of bleeding and manage appropriately.

Low blood cell counts. Lower than normal blood cell counts, including low neutrophils, platelets, or red blood cells, can occur. Your healthcare provider will monitor your blood counts regularly throughout treatment.

Cardiac arrhythmia. Cardiac arrhythmias may occur, including atrial fibrillation and atrial flutter, and second primary cancers, including skin cancers, have also occurred. Use sun protection when outside.

Liver problems. Severe, life-threatening, or fatal liver problems can happen during treatment. Your healthcare provider will do blood tests to check your liver before and during treatment. Tell your healthcare provider right away if you have stomach pain or discomfort, dark-colored urine, or yellowing of your skin or eyes.

Fetal Harm. This medicine can cause fetal harm. Females of reproductive potential should use effective contraception.

It is not known if this medicine is safe and effective in children.

Tell your doctor if you have or have ever had:

• an infection or have been told you are at an increased risk of infection;
• recent surgery, or plan to have surgery or a dental procedure;
• bleeding problems or are taking a blood thinner medicine;
• heart rhythm problems;
• high blood pressure;
• other types of cancer, including skin cancer; or
• kidney disease.
• liver problems.

Pregnancy

Tell your healthcare provider if you are pregnant, plan to become pregnant or become pregnant, as pirtobrutinib may harm an unborn baby. Do not use this medicine if you are pregnant. Your healthcare provider will do a pregnancy test before starting treatment in females who can become pregnant. Females who are able to become pregnant should use effective birth control (contraception) during treatment and for 1 week after their last dose. Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment.

Breastfeeding

Tell your healthcare provider if you are breastfeeding or planning to breastfeed, as it is not known if pirtobrutinib passes into your breast milk. Do not breastfeed during treatment and for 1 week after your last dose.

Common pirtobrutinib side effects

Common pirtobrutinib side effects may include bruising, tiredness, diarrhea, swelling, muscle, joint pain, bone pain, fever, chills, cough with mucus, chest pain, and feeling short of breath.

Serious pirtobrutinib side effects

Get emergency medical help if you have signs of an allergic reaction, such as hives, difficulty breathing, or swelling of your face, lips, tongue, or throat.

Other serious pirtobrutinib side effects. Call your doctor at once if you have:

• chest pressure, racing or pounding heartbeats, fluttering in your chest, feeling short of breath;
• signs of infection - fever, chills, sore throat, body aches, unusual tiredness, loss of appetite, bruising or bleeding;
• bleeding inside your body - weakness, dizziness; pink or brown urine; abnormal vaginal bleeding; bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;
• low blood cell counts - fever, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed or short of breath; or
• liver problems - stomach pain or discomfort, dark-colored urine, or yellowing of your skin or eyes.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Also, see the ‘Warnings section’.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Usual Adult Dose of Jaypirca for CLL, SLL, and MCLDose: 200 mg orally once dailyLength of Therapy: Until disease progression or unacceptable toxicity occurs.Dose modification: Your dose may be modified due to side effects, kidney impairment or because of interactions with other medications.

Jaypirca is available in 50 mg and 100 mg tablets.

If you miss a dose, take it as soon as you remember on the same day. If it has been more than 12 hours from the time you usually take pirtobrutinib, skip the missed dose, and take your next dose on the next day at your usual time.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking pirtobrutinib with certain other medicines may affect how Jaypirca or the other medicines work and can cause side effects.

Pirtobrutinib interacts with other drugs that are metabolized in a certain way. Tell your doctor if you are taking medicines that contain any of the following drugs:

• strong CYP3A inhibitors: cobicistat, ritonavir, itraconazole, ketoconazole, posaconazole, voriconazole, ceritinib, clarithromycin, idelalisib, nefazodone, nelfinavir
• strong CYP3A inducers: apalutamide, carbamazepine, enzalutamide, ivosidenib, lumacaftor, mitotane, phenytoin, rifampin, St. John’s wort
• moderate CYP3A inducers: bosentan, cenobamate, dabrafenib, efavirenz, etravirine, lorlatinib, pexidartinib, phenobarbital, primidone, sotorasib

Pirtobrutinib may also interact with grapefruit juice, though the effect varies widely among brands of grapefruit juice.For more information on interactions with pirtobrutinib, click on the link below.

• Store tablets at room temperature between 68°F to 77°F (20°C to 25°C).
• The tablets come in a bottle with a child-resistant cap.
• Keep all medicines out of the reach of children and pets.

Active ingredients: pirtobrutinib

Jaypirca Inactive ingredients: croscarmellose sodium, hypromellose acetate succinate, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and silicon dioxide.

The tablet film coating contains FD&C Blue #2, hypromellose, titanium dioxide, and triacetin.

Eli Lilly and Company.