RegulationAccelerated Approval (United States), Conditional marketing approval (China), Orphan Drug (South Korea), Priority Review (United States), Priority Review (China)

Structure/Sequence

Molecular FormulaC22H21F4N5O3

InChIKeyFWZAWAUZXYCBKZ-NSHDSACASA-N

CAS Registry2101700-15-4

Clinical Trials associated with Pirtobrutinib

NCT07624799

/ Not yet recruitingPhase 2IIT

Fixed Duration Treatment With Combined Pirtobrutinib and Short Course Immuno-chemotherapy in Fit Patients With Previously Untreated Symptomatic Chronic Lymphocytic Leukemia (CLL). A Phase II FILO Trial

The evidence base in support of fixed-duration, first-line approaches in medically fit patients with CLL is clearly strengthening, whether through combining targeted agents with immunochemotherapy or through chemotherapy-free combinations. The long-term PB MRD response rates with the investagators fixed-duration (15-month) immunochemotherapy approach remain the best to date, even compared to the new targeted agent combinations of ibrutinib-venetoclax or obinutuzumab-venetoclax.
The investigators' phase 2 ICLL07 trial in previously untreated fit CLL patients with a fixed-duration immunochemotherapy approach (with 4 cycles of FC-obinutuzumab and chemosparing strategy) carries a low risk for short and long term toxicities which still exist, including cardiac toxicities probably related to BTK inhibitors, moreover, two patients experienced treatment related myelodysplastic syndrome or acute myeloid leukemia beyond the end of treatment. Follow-up at 5,5 years from treatment start showed a persistent PB MRD benefit beyond end of treatment, high survival rates, and low long term toxicity with no difference in the durability of MRD response between the mutated and unmutated IGHV patients.
The investigators aim to explore the safety and efficacy of a fixed duration strategy combining a new BTK inhibitor with a favorable safety profile and a limited number of ICT courses.
The main goals and concerns are:
i) to ensure deep response and long lasting MRD ii) to reduce the duration of BTKi exposure and the risk of clonal evolution with the appearance of deleterious mutations iii) to limit the risk of hematopoietic secondary cancers (MDS/AML) by excluding patients in whom clonal hematopoiesis of undetermined potential (CHIP) is detected before inclusion and decreasing the number of courses of chemotherapy to 3 cycles. Moreover, patients with TP53 abnormalities will be excluded with a lower cut off (1% versus 10% in the previous studies) iv) to limit the risk of BTKi toxicity by using a non-covalent BTKi

Start Date01 Sep 2026

Sponsor / Collaborator-

NCT07220187

/ Not yet recruitingPhase 3IIT

A Randomized Phase III Study of Pirtobrutinib Plus R-CHOP vs. R-CHOP for Participants With Previously Untreated Richter Transformation (PIRAMID)

This phase III trial compares the effect of adding pirtobrutinib to the usual treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) to R-CHOP alone for the treatment of Richter transformation, which is when chronic lymphocytic leukemia or small lymphocytic lymphoma turns into large B-cell lymphoma, a more aggressive (faster-growing) form of lymphoma. Pirtobrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill cancer cells. It may also lower the body's immune response. Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's DNA and may kill cancer cells. It also blocks a certain enzyme needed for cell division and DNA repair. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Adding pirtobrutinib to R-CHOP may kill more cancer cells than R-CHOP alone in patients with Richter transformation.

Start Date31 Aug 2026

Sponsor / Collaborator

SWOG

[+1]

NCT07516093

/ Not yet recruitingPhase 3

A Phase 3, Randomized, Open-label, Multicenter Study of NX-5948 Versus Pirtobrutinib in Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

The study will evaluate the efficacy and safety of NX-5948 (bexobrutideg) versus pirtobrutinib in participants with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who are relapsed or refractory to prior covalent Bruton tyrosine kinase inhibitor (cBTKi) treatment.

Start Date01 Jun 2026

Sponsor / Collaborator

Nurix Therapeutics, Inc.

100 Clinical Results associated with Pirtobrutinib

100 Translational Medicine associated with Pirtobrutinib

100 Patents (Medical) associated with Pirtobrutinib

199

Literatures (Medical) associated with Pirtobrutinib

01 Jul 2026·AMERICAN JOURNAL OF HEMATOLOGY

Dissecting Pirtobrutinib Resistance in Mantle Cell Lymphoma Through Single‐Cell Multi‐Omics

Article

Author: Lukas M. Simon ; Heng-Huan Lee ; Michael Wang ; Joseph McIntosh ; Yijing Li ; Sairah Ahmed ; Wei Wang ; Yue Fei ; Fangfang Yan ; Jovanny Vargas ; Yang Liu

ABSTRACT:

Pirtobrutinib (PBN), a non‐covalent BTK inhibitor, has been approved by the FDA for relapsed/refractory mantle cell lymphoma (MCL); however, resistance to PBN has been observed. To dissect the molecular dynamics driving PBN resistance, we performed integrative single‐cell multi‐omic profiling (scRNA‐seq, scATAC‐seq, and scDNA‐seq) on longitudinal MCL patient samples. Our analyses revealed both genetic and non‐genetic routes of resistance: In some patients, resistance involves sequential copy number gains (e.g., 1q, 2p, and 8q) accompanied by transcriptomic reprogramming and epigenetic alterations, whereas in others, resistance occurs through non‐genetic mechanisms driven by transcriptional and epigenetic remodeling. Integration of scATAC‐seq and scRNA‐seq enabled gene regulatory network inference and in silico perturbation analysis, highlighting RAD21 and SMC3, core components of the cohesin complex, as chromatin regulators whose downregulation may re‐sensitize cells to PBN. A stem‐like malignant B cell population enriched in resistant samples exhibited features of metabolic reprogramming and epithelial‐mesenchymal transition. Together, our findings highlight heterogeneous, multi‐layered mechanisms of PBN resistance and suggest chromatin regulators as potential therapeutic targets to overcome PBN resistance in MCL.

23 Jun 2026·Blood Advances

Invasive fungal infections after Bruton tyrosine kinase inhibitor treatment: a systematic review and meta-analysis

Review

Author: Kates, Olivia S. ; Avery, Robin K. ; Srisurapanont, Karan ; Dioverti-Prono, M. Veronica ; Zhang, Sean X. ; Permpalung, Nitipong ; Baddley, John W. ; Meejun, Tanaporn ; Schulz, Cory A. ; Li, Lucy X. ; Manothummetha, Kasama

Abstract:

The epidemiology of invasive fungal infections (IFIs) among patients receiving Bruton tyrosine kinase inhibitors (BTKIs) remains incompletely characterized. We conducted a systematic review and meta-analysis of 88 studies including 23 737 patients to evaluate the prevalence and risk factors for IFIs in this population. Among 16 studies that applied the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium consensus definitions of IFIs, the pooled prevalence of proven/probable IFIs was 2.83% (95% confidence interval [CI], 1.97-4.06), with the highest prevalence observed in patients with central nervous system lymphoma (9.02%). Aspergillosis was the most frequently reported IFI (1.76%), followed by pneumocystosis, candidiasis, and cryptococcosis. The risk factors significantly associated with proven/probable IFIs were concurrent corticosteroid use (odds ratio [OR], 5.03; 95% CI, 2.31-10.92) and ≥3 previous lines of therapy (OR, 3.26; 95% CI, 1.54-6.88). Across clinical trials, the prevalence of fungal infections varied across BTKI agents, ranging from 2.50% with tirabrutinib, to 0.62% with pirtobrutinib. Data on antifungal and Pneumocystis jirovecii pneumonia prophylaxis were limited and inconclusive. Among clinical trials that reported fungal infections as adverse events, the prevalence of IFI was the highest in patients treated with tirabrutinib (2.50%), followed by zanubrutinib (2.13%), ibrutinib (1.75%), acalabrutinib (1.31%), orelabrutinib (1.08%), and pirtobrutinib (0.62%). Although some findings suggest a potential benefit in selected patients, current evidence remains insufficient to support broad prophylaxis recommendations. These results underscore the need for individualized risk assessment and further research to inform prevention strategies.

13 Jun 2026·EXPERT OPINION ON PHARMACOTHERAPY

From covalent to reversible: the expanding role of BTK inhibitors in chronic lymphocytic leukemia

Review

Author: Robak, Tadeusz

INTRODUCTION:

BTK inhibitors are divided into two groups based on their binding mechanism: covalent, irreversible (cBTKis), and non-covalent, reversible BTK inhibitors (ncBTKis). The covalent BTK inhibitors approved for use in CLL include the first-generation inhibitor ibutinib and second-generation BTK inhibitors, acalabrutinib and zanubrutinib. Non-covalent and reversible BTKs bind reversibly to BTK and remain effective even if C481S mutations are present.

AREAS COVERED:

This paper reviews recent developments in the use of BTK inhibitors in the treatment of chronic lymphocytic leukemia (CLL). Google Scholar and PubMed were initially searched for articles in English, published from 2016 to Aril 2026. In addition, a manual search was performed of conference proceedings from the last 5 years of The American Society of Hematology, American Society of Clinical Oncology and the European Hematology Association.

EXPERT OPINION:

Covalent BTKis and ncBTKis revolutionized CLL treatment in the last decade Three cBTKis, ibrutinib, acalabrutinib, and zanubrutinib, are approved by FDA for the treatment of CLL. The most advanced ncBTKis are pirtobrutinib and nemtabrutinib. Of these, only pirtobrutinib is recommended for patients refractory to cBTKis. However, further clinical trials focusing on dose optimization are needed, as well as combination studies with existing drugs and novel agents.

223

News (Medical) associated with Pirtobrutinib

30 Jun 2026

·www.prnewswire.com

Innovent Biologics and Lilly Enter into Commercialization Agreement for Verzenios® (abemaciclib) in Mainland China

SAN FRANCISCO and SUZHOU, China, June 30, 2026 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures, and commercializes high-quality medicines for the treatment of oncology, autoimmune, cardiovascular and metabolic, ophthalmology and other major disease areas, and Eli Lilly and Company (NYSE: LLY) today jointly announced that they have entered into a distribution and promotion agreement regarding Lilly's CDK4 & 6 inhibitor Verzenios® (abemaciclib) in mainland China: Innovent will be responsible for the importation, marketing, distribution and promotion of Verzenios® (abemaciclib) in mainland China; Lilly will continue to be responsible for manufacturing, supply, and development for the product. Verzenios® (abemaciclib), developed by Lilly, is a CDK4 & 6 inhibitor that has been approved in China for multiple indications, including: (1) Early Breast Cancer: in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive early breast cancer at high risk of recurrence. (2) Locally Advanced or Metastatic Breast Cancer: a) For the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer: In combination with an aromatase inhibitor as initial endocrine-based therapy in postmenopausal women. In combination with fulvestrant for patients who have experienced disease progression following prior endocrine therapy. b) In combination with imlunestrant: for the treatment of adult patients with estrogen receptor (ER)-positive, HER2-negative, ESR1-mutated locally advanced or metastatic breast cancer who have previously received endocrine therapy. The product was included in the National Reimbursement Drug List (NRDL) Class B in 2021, becoming the first CDK4 & 6 inhibitor covered by national reimbursement in China. In 2025, it successfully renewed its NRDL listing, achieving full coverage across both early and advanced breast cancer indications. Under the agreement, Innovent will hold sole commercialization rights for Verzenios® (abemaciclib) in mainland China, while Lilly, as the Marketing Authorization Holder (MAH), will continue to be responsible for manufacturing, supply, and ongoing product development. This collaboration combines Innovent's experienced oncology commercialization team and extensive market reach in China with Lilly's expertise in innovative medicine development and lifecycle management, further enhancing access to this important therapy and benefiting more breast cancer patients across the country. Dr. Michael Yu, Founder, Chairman of the Board and CEO of Innovent, stated: "We are delighted to further deepen our strategic partnership with Lilly through this eighth collaboration, bringing the number of our partnered, on-market products in China to seven. This also marks the 19th product in Innovent's portfolio. Enhancing patient access to high-quality, innovative medicines has always been at the core of Innovent's mission. Leveraging our established commercial infrastructure and strong market presence in China, we remain focused on addressing critical unmet needs in major oncology indications. Breast cancer, one of the most prevalent and life–threatening malignancies among women, is a strategic priority within Innovent's oncology portfolio. Through this commercial collaboration with Lilly on Verzenios® (abemaciclib) – backed by its robust clinical efficacy, comprehensive labeled indications and national reimbursement coverage – we are expanding our presence in this area, laying a solid foundation for our pipeline development and market expansion deliver lasting benefits to patients in breast cancer." Huzur Devletsah, Lilly Group Vice President and China General Manager, said: "For 150 years, Lilly has remained committed to putting health above all, advancing human health through scientific innovation and expanding access through collaboration. This agreement for Verzenios® (abemaciclib) is an important step in strengthening patient access in China, combining Lilly's global R&D expertise with Innovent's commercialization capabilities in China. Looking ahead, Lilly will continue to advance its oncology efforts in China. Since the beginning of this year, we have secured approvals for one new medicine (with two indications) and two new additional indications for on market products in China, including Inluriyo®, which has become the first and currently only approved precision therapy in China only targeting ESR1-mutated advanced breast cancer, accelerating the introduction of globally innovative therapies and addressing unmet medical needs." About Innovent Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 19 products in the market. It has 1 asset in NMPA NDA review, 5 assets in Phase 3 or pivotal clinical trials and 14 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Lilly, Takeda, Pfizer, Roche, Sanofi, Incyte, LG Chem and MD Anderson Cancer Center. Guided by the motto, "Start with Integrity, Succeed through Action" Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit , or follow Innovent on Facebook and LinkedIn. Statement: 1) Innovent does not recommend the use of any unapproved drug (s)/indication (s). 2) Ramucirumab (Cyramza) and Selpercatinib (Retsevmo), Pirtobrutinib (Jaypirca) and abemaciclib (Verzenios) were developed by Eli Lilly and Company. Disclaimer: Innovent does not recommend any off-label usage. About Lilly Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. Forward-Looking Statements of Innovent Biologics This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly. These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions. SOURCE Innovent Biologics 21% more press release views with Request a Demo

Drug ApprovalLicense out/inNDA

02 Jul 2026

·www.prnewswire.com

Lilly's Jaypirca (pirtobrutinib) recommended by CHMP for approval in the European Union for adults with chronic lymphocytic leukemia (CLL) across all lines of therapy

The positive opinion is based on results from the Phase 3 BRUIN CLL-313 and BRUIN CLL-314 trials, previously presented at the 2025 American Society of Hematology Annual Meeting and published in The Journal of Clinical Oncology BRUIN CLL-313 is the first Phase 3 study to evaluate a non-covalent BTK inhibitor exclusively in patients with treatment-naïve CLL and BRUIN CLL-314 is the first Phase 3 CLL trial to compare non-covalent and covalent BTK inhibitors, as well as the first to compare any BTK inhibitors in the treatment-naïve setting If granted marketing authorization, this would expand pirtobrutinib's indication as a treatment option for patients with CLL in the European Union across all lines of therapy June 26, 2026 -- Eli Lilly and Company (NYSE: LLY) today announced that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for Jaypirca (pirtobrutinib), a non-covalent Bruton tyrosine kinase (BTK) inhibitor, for the treatment of adults with chronic lymphocytic leukemia (CLL) across all lines of therapy and regardless of prior BTK inhibitor treatment. Following this positive opinion, the application is now referred to the European Commission for final action. The European Commission's decision is expected in the next one to two months. "Results from BRUIN CLL-313 and BRUIN CLL-314 provide compelling evidence that pirtobrutinib can make a meaningful difference for people living with CLL across multiple lines of therapy," said Paolo Ghia, M.D., professor, medical oncology, Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milano, Italy. "The strong efficacy and tolerability demonstrated in these trials underscores the clinical value pirtobrutinib may offer patients. This positive opinion from the CHMP is an exciting and significant milestone, bringing us closer to a future where pirtobrutinib is an option for more people with CLL across the European Union." Results from BRUIN CLL-313 and BRUIN CLL-314 were presented at the American Society of Hematology (ASH) Annual Meeting and Exposition in December 2025 and published in The Journal of Clinical Oncology. "Based on the strong results from the BRUIN CLL-313 and CLL-314 studies, we believe Jaypirca has the potential to serve as a meaningful new option for newly diagnosed patients and those who have not yet received a BTK inhibitor," said Jacob Van Naarden, executive vice president and president of Lilly Oncology. "Thanks to the impact of contemporary CLL treatments, many patients may receive fewer lines of therapy over their lifetime, making treatment choices in earlier lines profoundly important. This CHMP opinion represents a step toward an important global approval for Jaypirca in this indication and reflects our ambition to make Jaypirca available to every CLL patient who may benefit, at any line of therapy. Today, we are on the brink of making that a reality across the European Union as we await the European Commission's final decision." Lilly has also submitted these results to the U.S. Food and Drug Administration (FDA) for approval for adult patients with CLL, with a decision expected in the second half of 2026. BRUIN CLL-313 is a Phase 3, global, randomized, open-label study of pirtobrutinib versus chemoimmunotherapy (BR) in people with CLL/SLL without 17p deletions who have not been previously treated. The trial enrolled 282 patients who were randomized 1:1 to receive pirtobrutinib (200 mg orally, once daily) or BR per labeled doses. BR is a chemoimmunotherapy regimen used in the treatment of CLL. The primary endpoint is PFS as assessed by blinded IRC. Secondary endpoints include investigator and IRC assessed ORR, duration of response (DoR), and PFS, OS, time to next treatment (TTNT), safety and tolerability and patient-reported outcomes (PRO). BRUIN CLL-314 is a Phase 3, randomized, open-label study of Jaypirca (pirtobrutinib) versus Imbruvica (ibrutinib) in patients with CLL/SLL who were either treatment-naïve, or who were previously treated and were BTK inhibitor-naïve. The trial enrolled 662 patients who were randomized 1:1 to receive pirtobrutinib (200 mg orally, once daily) or ibrutinib (420 mg orally, once daily). The primary endpoint is ORR as assessed by blinded IRC. Secondary endpoints include investigator and IRC-assessed PFS, duration of response (DoR) and event-free survival (EFS), and time to next treatment (TTNT), OS, safety and tolerability, and patient-reported outcomes (PRO). Jaypirca (pirtobrutinib, formerly known as LOXO-305) (pronounced jay-pihr-kaa) is a highly selective (300 times more selective for BTK versus 98% of other kinases tested in preclinical studies), non-covalent inhibitor of the enzyme BTK.1 BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).2,3 Jaypirca is a U.S. FDA-approved oral prescription medicine, 100 mg or 50 mg tablets taken as a once-daily 200 mg dose with or without food until disease progression or unacceptable toxicity. CLL is a form of slow-growing non-Hodgkin lymphoma that develops from white blood cells known as lymphocytes.4,5 CLL is one of the most common types of leukemia in adults.6 There are roughly 100,000 new cases of CLL globally each year, and the overall incidence of CLL in Europe is approximately 4.92 cases per 100,000 persons per year.6,7 In CLL, the cancer cells are present in the blood.6 Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. Endnotes & References Mato AR, Shah NN, Jurczak W, et al. Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study. Lancet. 2021;397(10277):892-901. doi:10.1016/S0140-6736(21)00224-5 Hanel W, Epperla N. Emerging therapies in mantle cell lymphoma. J Hematol Oncol. 2020;13(1):79. Published 2020 Jun 17. doi:10.1186/s13045-020-00914-1 Gu D, Tang H, Wu J, Li J, Miao Y. Targeting Bruton tyrosine kinase using non-covalent inhibitors in B cell malignancies. J Hematol Oncol. 2021;14(1):40. Published 2021 Mar 6. doi:10.1186/s13045-021-01049-7 Mukkamalla SKR, Taneja A, Malipeddi D, et al. Chronic Lymphocytic Leukemia. [Updated 2023 Feb 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470433/ The Leukemia and Lymphoma Society. NHL Subtypes. Access here: https://www.lls.org/lymphoma/non-hodgkin-lymphoma/nhl-subtypes. Accessed on October 25, 2023. Ou Y, Long Y, Ji L, et al. Trends in Disease Burden of Chronic Lymphocytic Leukemia at the Global, Regional, and National Levels From 1990 to 2019, and Projections Until 2030: A Population-Based Epidemiologic Study. Front Oncol. 2022;12:840616. Published 2022 Mar 10. doi:10.3389/fonc.2022.840616 Sant M, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood. 2010. 116:3724–34. https://pubmed.ncbi.nlm.nih.gov/20664057/ The content above comes from the network. if any infringement, please contact us to modify.

Clinical ResultASHDrug ApprovalASCO

16 Jun 2026

·www.prnewswire.com

Lilly's Jaypirca (pirtobrutinib) significantly reduced the risk of disease progression or death by 45% when added to a venetoclax time-limited regimen in people with previously treated CLL/SLL

BRUIN CLL-322 is the first Phase 3 study to demonstrate superiority over a venetoclax-containing control arm in CLL, and, with the majority of patients previously treated with a covalent BTK inhibitor, reflects current practice patterns These data will be highlighted in a late-breaking oral presentation at the 2026 European Hematology Association (EHA) Annual Meeting June 14, 2026 -- Eli Lilly and Company (NYSE: LLY) today announced results from the Phase 3 BRUIN CLL-322 clinical trial of Jaypirca (pirtobrutinib), a non-covalent Bruton tyrosine kinase (BTK) inhibitor, plus venetoclax and rituximab versus venetoclax and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). The study met its primary endpoint of independent review committee (IRC)-assessed progression-free survival (PFS), demonstrating that the addition of pirtobrutinib to a two-year venetoclax plus rituximab regimen reduced the risk of disease progression or death by 45% (HR=0.55 [95% CI, 0.40-0.75]; p=0.0001). These data will be highlighted in a late-breaking oral presentation at the 2026 European Hematology Association (EHA) Annual Meeting taking place in Stockholm, Sweden, as well as featured in the meeting's press program. "These results from BRUIN CLL-322 show that the addition of pirtobrutinib as part of a time-limited regimen further enhanced an already effective treatment and extended the duration of remission for patients with previously treated CLL. Importantly, the study provides the first robust evidence for such an approach in patients who received a prior BTK inhibitor," said Matthew S. Davids, M.D., M.M.Sc., Chief of the Division of Lymphoma at Dana-Farber Cancer Institute, who is the lead author on the study. "Time-limited regimens are an important option in CLL care and provide patients with meaningful treatment-free intervals. In the context of the modern CLL treatment landscape, where many patients may only receive two lines of therapy, these results speak to the potential benefits that improving second-line therapy can have. Our study has the potential to establish a new standard of care in this population." BRUIN CLL-322 enrolled 639 relapsed or refractory patients, with 79.8% having prior covalent BTK inhibitor exposure, who were randomized 1:1 to receive pirtobrutinib plus venetoclax and rituximab (PVR, n=321) or venetoclax and rituximab alone (VR, n=318). Patients in the PVR arm received three cycles of pirtobrutinib and the first three cycles of rituximab before venetoclax was introduced. The efficacy results are based on a Feb. 2, 2026 data cutoff. At a median follow-up of 27.3 months, the primary endpoint of IRC-assessed PFS was significantly improved with the addition of pirtobrutinib to VR compared to VR alone (HR=0.55 [95% CI, 0.40-0.75]; p=0.0001). Median PFS in the PVR arm was not reached (95% CI, 43.3-NE), versus 39.7 months (95% CI, 35.9-NE) in the VR arm. The PFS results were consistent across prespecified subgroups, including patients with prior covalent BTK inhibitor exposure (PVR: not reached [95% CI, 41.5-NE] versus VR: 36.2 months [95% CI, 33.2-NE]), those who discontinued prior covalent BTK inhibitor due to progressive disease (PVR: 43.3 months [95% CI, 39.2-NE] versus VR: 33.2 months [95% CI, 28.3-37.5]), as well as those with high-risk features such as unmutated IGHV, TP53 mutation and/or 17p deletion, and/or complex karyotype. In an exploratory analysis of second-line patients whose disease progressed after a first-line covalent BTK inhibitor, the median PFS was not reached (95% CI, 30.1-NE) in the PVR arm and was 28.3 months (95% CI, 20.5-NE) in the VR arm (HR=0.32 [95% CI, 0.14-0.73]), with 24-month PFS rates of 88% (95% CI, 75.7-94.6) and 52% (95% CI, 34.7-66.2), respectively, and consistent benefit was observed regardless of the specific prior covalent BTK inhibitor received. Overall survival (OS), a key secondary endpoint, was not yet mature at this analysis (HR=0.89 [95% CI, 0.57-1.40]), and final testing of OS superiority is planned at a future date. An additional secondary endpoint, time to next treatment (TTNT), consistently favored the pirtobrutinib combination regimen (HR=0.50 [95% CI, 0.35-0.70]; nominal p<0.0001). BRUIN CLL-322 is a global, randomized, open-label, Phase 3 study comparing time-limited pirtobrutinib plus venetoclax and rituximab versus venetoclax and rituximab in previously treated CLL/SLL patients. The trial enrolled 639 patients, who were randomized 1:1 to receive pirtobrutinib (200 mg, once daily) plus venetoclax and rituximab per their labeled doses or venetoclax and rituximab alone. The primary endpoint is PFS as assessed by blinded IRC. Secondary endpoints include PFS as assessed by investigator, OS, TTNT, event-free survival, overall response rate, time to worsening of CLL/SLL-related symptoms, time to worsening of physical functioning, safety and tolerability. Jaypirca (pirtobrutinib) (pronounced jay-pihr-kaa) is a highly selective (300 times more selective for BTK versus 98% of other kinases tested in preclinical studies), non-covalent inhibitor of the enzyme BTK.1 BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).2,3 Jaypirca is a U.S. FDA-approved oral prescription medicine, 100 mg or 50 mg tablets taken as a once-daily 200 mg dose with or without food until disease progression or unacceptable toxicity. Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. Endnotes & References Mato AR, Shah NN, Jurczak W, et al. Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study. Lancet. 2021;397(10277):892-901. doi:10.1016/S0140-6736(21)00224-5 Hanel W, Epperla N. Emerging therapies in mantle cell lymphoma. J Hematol Oncol. 2020;13(1):79. Published 2020 Jun 17. doi:10.1186/s13045-020-00914-1 Gu D, Tang H, Wu J, Li J, Miao Y. Targeting Bruton tyrosine kinase using non-covalent inhibitors in B cell malignancies. J Hematol Oncol. 2021;14(1):40. Published 2021 Mar 6. doi:10.1186/s13045-021-01049-7 The content above comes from the network. if any infringement, please contact us to modify.

Clinical ResultDrug ApprovalAccelerated Approval

100 Deals associated with Pirtobrutinib

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Refractory Small Lymphocytic Lymphoma	Australia	Eli Lilly Australia Pty Ltd.	05 Mar 2026
Chronic lymphocytic leukaemia refractory	United States	Loxo Oncology, Inc.	02 Dec 2025
Recurrent Chronic Lymphoid Leukemia	United States	Loxo Oncology, Inc.	02 Dec 2025
Lymphoma	Canada	Eli Lilly Canada, Inc.	01 Oct 2025
Chronic Lymphocytic Leukemia	United States	Loxo Oncology, Inc.	01 Dec 2023
Small Lymphocytic Lymphoma	United States	Loxo Oncology, Inc.	01 Dec 2023
Mantle-Cell Lymphoma	European Union	Eli Lilly Nederland BV	30 Oct 2023
Mantle-Cell Lymphoma	Iceland	Eli Lilly Nederland BV	30 Oct 2023
Mantle-Cell Lymphoma	Liechtenstein	Eli Lilly Nederland BV	30 Oct 2023
Mantle-Cell Lymphoma	Norway	Eli Lilly Nederland BV	30 Oct 2023
Mantle cell lymphoma recurrent	United States	Loxo Oncology, Inc.	27 Jan 2023
Mantle cell lymphoma refractory	United States	Loxo Oncology, Inc.	27 Jan 2023

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Recurrent Follicular Lymphoma	Phase 2	United States	Eli Lilly & Co.	17 Nov 2025
Refractory Follicular Lymphoma	Phase 2	United States	Eli Lilly & Co.	17 Nov 2025
Purpura, Thrombocytopenic, Idiopathic	Phase 2	United States	Eli Lilly & Co.	11 Sep 2025
Purpura, Thrombocytopenic, Idiopathic	Phase 2	China	Eli Lilly & Co.	11 Sep 2025
Purpura, Thrombocytopenic, Idiopathic	Phase 2	Denmark	Eli Lilly & Co.	11 Sep 2025
Purpura, Thrombocytopenic, Idiopathic	Phase 2	France	Eli Lilly & Co.	11 Sep 2025
Purpura, Thrombocytopenic, Idiopathic	Phase 2	Italy	Eli Lilly & Co.	11 Sep 2025
Purpura, Thrombocytopenic, Idiopathic	Phase 2	Poland	Eli Lilly & Co.	11 Sep 2025
Purpura, Thrombocytopenic, Idiopathic	Phase 2	South Korea	Eli Lilly & Co.	11 Sep 2025
Purpura, Thrombocytopenic, Idiopathic	Phase 2	Spain	Eli Lilly & Co.	11 Sep 2025

Clinical Result

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Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05023980 (BRUIN CLL-313, ASCO2026)	Phase 3	Chronic Lymphocytic Leukemia \| Small Lymphocytic Lymphoma First line	253	Pirtobrutinib	anlvbtcfok(typzxxgldp) = Any-grade infection occurred in 59.9% of pts; neutropenia in 18.3% and grade ≥3 bleeding in 2.4%. Any-grade hypertension occurred in 10.7% of pts and atrial fibrillation/flutter was reported in 2.8%. czyqzocvzj (wzzjcaiutg )	Positive	29 May 2026
NCT05023980 (BRUIN CLL-313, EHA2026)	Phase 3	Chronic Lymphocytic Leukemia \| Small Lymphocytic Lymphoma First line	253	Pirtobrutinib (CLL-313)	basnhjenpi(vweggnptcq) = lxkscjofav jwkvtxtczt (abojormfev, 93.3 - 99.3) View more	Positive	21 May 2026
				Pirtobrutinib (CLL-314)	basnhjenpi(vweggnptcq) = rwiscpuhcl jwkvtxtczt (abojormfev, 91.5 - 99.1) View more
NCT07342478 (ROCKET-CLL, EHA2026)	Phase 3	Chronic Lymphocytic Leukemia \| Small Lymphocytic Lymphoma	306	Rocbrutinib	cyhdsvrlto(asgcmydjwe) = gxqkwcabrr rmlhsotrmy (rcumitvbls ) View more	Positive	12 May 2026
				Pirtobrutinib	cyhdsvrlto(asgcmydjwe) = wjdstcribl rmlhsotrmy (rcumitvbls ) View more
NCT05023980 (BRUIN-CLL-313, EHA2026)	Phase 3	Chronic Lymphocytic Leukemia \| Small Lymphocytic Lymphoma First line	282	Pirtobrutinib	ghlzlyvkzi(tkkqtrlflm) = hmcrkrahvo gjrdlcfdck (onneqvmnlc ) View more	Positive	12 May 2026
				Bendamustine plus Rituximab	ghlzlyvkzi(tkkqtrlflm) = yqyvkhvlgq gjrdlcfdck (onneqvmnlc ) View more
EHA2026	Not Applicable	Chronic Lymphocytic Leukemia	50	Pirtobrutinib (Observation)	hcwpilxatz(wfadxrijnt) = reported in 11 patients: 3 had an infection, 3 had neutropenia; febrile neutropenia, diarrhea, chest pain, pulmonary toxicity, and increased transaminase levels were recorded in 1 patient each. One patient had fungal pneumonia, and 1 patient had an episode of atrial fibrillation (grade not reported). pzxghvelud (uupvihkymv )	Positive	12 May 2026
EHA2026	Not Applicable	Mantle cell lymphoma refractory	208	Pirtobrutinib	ptczjptyjt(eaakvrpwuz) = Infections accounted for 41% and hematologic toxicities for 28% of all grade ≥3 AEs. Four AEs of grade 5 occurred, however deaths were dominantly attributable to disease progression. emybjaqbpr (yqzjzburmz ) View more	Positive	12 May 2026
				Current standard of care (SoC)
NCT06333262 (EHA2026)	Phase 2	Chronic Lymphocytic Leukemia	60	ObinutuzumabPirtobrutinib + ObinutuzumabPirtobrutinib (Chronic Lymphocytic Leukemia)	qsumbkzblt(xmibpaudjy) = gcfhbnlhzz ajrfdtzskd (ncsxktzldy ) View more	Positive	12 May 2026
NCT03740529 (BRUIN, Pubmed \| Lancet Haematol)	Phase 1/2	Waldenstrom's macroglobulinaemia refractory	80	Pirtobrutinib	czxlxuhsqz(tdnaqvgsmr) = unrelated to treatment kxohbppzic (vhdgtwilwp ) View more	Positive	01 May 2026
				Pirtobrutinib (previous covalent BTK inhibitors)
NCT05254743 (Pubmed \| J Clin Oncol)	Phase 3	Chronic Lymphocytic Leukemia \| Small Lymphocytic Lymphoma	662	Pirtobrutinib	anymjcaxxi(tpotjwcgmn) = jbmktmokqk grcbgsnkas (lvrjzpckdl, 82.9 - 90.4)	Non-inferior	20 Feb 2026
				Ibrutinib	anymjcaxxi(tpotjwcgmn) = mlxqnsgdom grcbgsnkas (lvrjzpckdl, 73.7 - 82.9)
NCT05023980 (BRUIN CLL-313, Pubmed \| J Clin Oncol)	Phase 3	Chronic Lymphocytic Leukemia \| Small Lymphocytic Lymphoma First line	282	Pirtobrutinib	oilsioofui(qjlenliqtl) = xfqbuzziib lcrswhblrm (mwtotfxtvs, 87.6 - 96.5) View more	Positive	20 Feb 2026
				Bendamustine plus rituximab (BendaR)	oilsioofui(qjlenliqtl) = quwegnwvlh lcrswhblrm (mwtotfxtvs, 61.5 - 78.1) View more

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