Pirtobrutinib for Chronic Lymphocytic Leukemia
Recruiting in Palo Alto (17 mi)
+136 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Loxo Oncology, Inc.
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?The main purpose of this study is to assess the efficacy and safety of 3 dose levels of Pirtobrutinib in participants with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), who have received 1-3 lines of treatment including a covalent Bruton tyrosine kinase (BTK) inhibitor. The study is expected to last approximately 3 years.
What data supports the effectiveness of the drug Pirtobrutinib for Chronic Lymphocytic Leukemia?
Pirtobrutinib has shown high response rates in patients with chronic lymphocytic leukemia who are resistant to other BTK inhibitors, and it has been approved for use in mantle cell lymphoma. It is particularly promising for patients who need treatment after other therapies have failed, with ongoing studies to further understand its effectiveness.
12456What is known about the safety of Pirtobrutinib in humans?
Pirtobrutinib has been studied for safety in patients with mantle cell lymphoma and chronic lymphocytic leukemia. Common side effects include fatigue, muscle pain, diarrhea, swelling, shortness of breath, pneumonia, and bruising. There are warnings for potential infections, bleeding, low blood cell counts, irregular heartbeats, and risk of new cancers.
23467How is the drug Pirtobrutinib different from other treatments for chronic lymphocytic leukemia?
Pirtobrutinib is unique because it is a noncovalent (reversible) Bruton's tyrosine kinase inhibitor, which means it can be effective even when other similar drugs stop working. This makes it a promising option for patients who have developed resistance to existing treatments.
24567Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
Eligibility Criteria
This trial is for people with a type of blood cancer called CLL/SLL who have tried some treatments but still need help. They should be able to take pills, had up to 3 prior treatments including a specific drug type (BTK inhibitor), and be well enough to do daily activities.Inclusion Criteria
I have been diagnosed with CLL/SLL according to the latest criteria.
I have been treated for CLL/SLL before.
I can swallow pills.
I can take care of myself and am up and about more than half of my waking hours.
I have been treated with a BTK inhibitor.
I've had 1 to 3 treatments for my CLL/SLL.
Exclusion Criteria
I have been treated with specific types of medication for my condition.
I've had severe bleeding from a BTK inhibitor treatment.
My condition has progressed to a more aggressive form of cancer.
My CLL/SLL may have affected my brain or spinal cord.
Participant Groups
The study tests three doses of Pirtobrutinib in patients whose CLL/SLL has come back or didn't respond after treatment. It checks how well the drug works and its safety over about 3 years.
3Treatment groups
Experimental Treatment
Active Control
Group I: Pirtobrutinib Dose 3Experimental Treatment1 Intervention
Pirtobrutinib administered orally.
Group II: Pirtobrutinib Dose 2Experimental Treatment1 Intervention
Pirtobrutinib administered orally.
Group III: Pirtobrutinib Standard Dose (Dose 1)Active Control1 Intervention
Pirtobrutinib administered orally.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Ironwood Cancer & Research CentersChandler, AZ
City of Hope National Medical CenterDuarte, CA
City of Hope National Medical CenterIrvine, CA
Palo Alto Medical Foundation Research Institute (PAMFRI)Palo Alto, CA
More Trial Locations
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Who is running the clinical trial?
Loxo Oncology, Inc.Lead Sponsor
Eli Lilly and CompanyIndustry Sponsor
References
Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. [2021]Ibrutinib (Imbruvica): a novel targeted therapy for chronic lymphocytic leukemia.
Phase I Trial of the Pan-PI3K Inhibitor Pilaralisib (SAR245408/XL147) in Patients with Chronic Lymphocytic Leukemia (CLL) or Relapsed/Refractory Lymphoma. [2021]This phase I expansion-cohort study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the pan-PI3K inhibitor pilaralisib (SAR245408/XL147) in patients with chronic lymphocytic leukemia (CLL) or relapsed or refractory lymphoma.
Adverse drug events associated with ibrutinib for the treatment of elderly patients with chronic lymphocytic leukemia: A systematic review and meta-analysis of randomized trials. [2022]Chronic lymphocytic leukemia (CLL) is a rare hematological malignancy classified in the non-Hodgkin's lymphoma category. Ibrutinib, a first-in-class Bruton tyrosine kinase inhibitor has been approved for use in the treatment of CLL. This drug has shown beneficial effects including a higher overall response rate, sustained remissions, and a tolerable toxicity level. In this meta-analysis, we aimed to compare the adverse drug events which were associated with the use of ibrutinib for the treatment of patients with CLL.
Pirtobrutinib: a new hope for patients with BTK inhibitor-refractory lymphoproliferative disorders. [2023]Patients with lymphoproliferative disorders such as chronic lymphocytic leukemia and mantle cell lymphoma (MCL) who are resistant to covalent Bruton tyrosine kinase inhibitors (cBTKis), especially if also venetoclax refractory, have an unmet therapeutic need. Pirtobrutinib, a noncovalent BTKi, achieves high response rates in patients who are refractory to cBTKi, regardless of mechanism of cBTKi resistance. This led to recent accelerated US Food and Drug Administration approval in MCL. The toxicity profile in early studies suggests suitability for use in combination approaches. We summarize existing preclinical and clinical data for pirtobrutinib.
Pirtobrutinib after a Covalent BTK Inhibitor in Chronic Lymphocytic Leukemia. [2023]Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) have poor outcomes after the failure of covalent Bruton's tyrosine kinase (BTK) inhibitor treatment, and new therapeutic options are needed. Pirtobrutinib, a highly selective, noncovalent (reversible) BTK inhibitor, was designed to reestablish BTK inhibition.
Non-Covalent Bruton's Tyrosine Kinase Inhibitors in the Treatment of Chronic Lymphocytic Leukemia. [2023]Covalent Bruton's tyrosine kinase inhibitors (cBTKi) have led to a paradigm shift in the treatment of chronic lymphocytic leukemia (CLL). These targeted oral therapies are administered as standard treatments in both the front-line and relapsed and/or refractory settings. Given their administration as a continuous therapy with a "treat-to-progression" strategy, limitations of their use include discontinuation due to toxicity or from progression of the disease. Non-covalent Bruton's tyrosine kinase inhibitors (ncBTKi) distinguish themselves by binding reversibly to the BTK target, which may address the limitations of toxicity and acquired resistance seen with cBTKi. Several ncBTKis have been studied preclinically and in clinical trials, including pirtobrutinib and nemtabrutinib. Pirtobrutinib, which is now FDA approved for relapsed and/or refractory mantle cell lymphoma (MCL), has shown outstanding safety and preliminary efficacy in CLL in phase 1 and 2 clinical trials, with phase 3 trials underway. This agent may fill an unmet medical need for CLL patients requiring treatment after a cBTKi. Pirtobrutinib is particularly promising for the treatment of "double exposed" CLL, defined as CLL requiring treatment after both a cBTKi and venetoclax. Some patients have now developedacquired resistance to pirtobrutinib, and resistance mechanisms (including novel acquired mutations in BTK outside of the C481 position) have been recently described. Further study regarding the mechanisms of resistance to pirtobrutinib in patients without prior cBTKi exposure, as well as the potential for cross-resistance between cBTKi and ncBTKis, may be important to help inform where ncBTKis will ultimately fit in the treatment sequencing paradigm for CLL. An emerging clinical challenge is the treatment of CLL after ncBTKi discontinuation. Novel therapeutic strategies are being investigated to address the treatment of patients following disease progression on ncBTKis. Such strategies include novel agents (BTK degraders, bispecific antibody therapy, CAR T-cell therapy, PKC-beta inhibitors) as well as combination approaches incorporating a ncBTKi (e.g., pirtobrutinib and venetoclax) that may help overcome this acquired resistance.
FDA Approval Summary: Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma. [2023]In January 2023, the U.S. Food and Drug Administration granted accelerated approval to pirtobrutinib for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor. Approval was based on BRUIN, a single-arm study of pirtobrutinib monotherapy in patients with B-cell malignancies. Efficacy was based on independent review committee- assessed overall response rate (ORR) supported by durability of response in 120 patients with relapsed or refractory MCL who had received a prior BTK inhibitor and received the approved pirtobrutinib dosage of 200 mg once daily. The ORR was 50% (95% confidence interval [CI]: 41, 59) and the complete response rate was 13% (95% CI: 7, 20), with an estimated median duration of response of 8.3 months. The most common non-hematologic adverse reactions were fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. Warnings and Precautions in labeling include infection, hemorrhage, cytopenias, atrial arrhythmias, and second primary malignancies. Postmarketing studies were required to evaluate longer-term safety of pirtobrutinib and to verify the clinical benefit of pirtobrutinib. This article summarizes key aspects of the regulatory review, including the indication statement, efficacy and safety considerations, and postmarketing requirements.