On December 7, 2025 Incyte (Nasdaq:INCY) reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to INCA033989, a first-in-class mutant calreticulin (mutCALR)-targeted monoclonal antibody, for the treatment of patients with essential thrombocythemia (ET) harboring a Type 1 CALR mutation who are resistant or intolerant to at least one cytoreductive therapy.

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ET is a chronic myeloproliferative neoplasm (MPN) characterized by persistently elevated platelet counts due to abnormal blood cell production in the bone marrow. CALR mutations are the second most common oncogenic driver mutation and are observed in 25% of patients with ET. A 52-bp deletion, also known as a Type 1 mutation, occurs in 55% of patients with a CALR mutation, and is associated with the highest risk of transformation to myelofibrosis (MF) among all ET patients.

"Incyte has long been committed to improving outcomes for patients with MPNs, and this Breakthrough Therapy designation underscores the potential of INCA033989 to be a novel therapy that could significantly transform the treatment of ET patients, who today have limited treatment options," said Pablo J. Cagnoni, M.D., President and Head of Research and Development, Incyte. "The designation allows us to expedite the development pathway for INCA033989 in patients with Type 1 mutations. Looking ahead, we plan to initiate a Phase 3 program evaluating INCA033989 in ET patients with all types of CALR mutations in mid-2026, following alignment with regulators in the first half of next year."

The FDA Breakthrough Therapy Designation was supported by the early Phase 1 data evaluating INCA033989 in ET patients with a Type 1 CALR mutation available at the time of submission.

The preliminary Phase 1 data were presented earlier this year at the 2025 European Hematology Association (EHA) (Free EHA Whitepaper) Congress. In the study, INCA033989 was well-tolerated and demonstrated rapid and durable normalization of platelet counts across evaluated doses, with greater responses seen at higher doses across both mutation types. Updated results from the Phase 1 dose escalation and expansion trial are planned for presentation at the 2025 ASH (Free ASH Whitepaper) Annual Meeting in Orlando (Session 634; Publication #1024; December 8, 4:30-6:00 p.m. ET).

Incyte plans to develop INCA033989 for patients with Type 1 and non-Type 1 CALR mutations and, following discussions with regulatory agencies, plans to initiate a registrational program evaluating patients with ET with a Type 1 or non-Type 1 CALR mutation who are resistant or intolerant to at least one cytoreductive therapy in the first half of next year.

About Essential Thrombocythemia
Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN) characterized by persistently elevated platelet counts due to abnormal blood cell production in the bone marrow. People living with ET are at increased risk for blood clots and bleeding and a proportion of patients may progress over time to myelofibrosis or acute leukemia.

About Mutations in Calreticulin (mutCALR)
Calreticulin (CALR) is a protein involved in the regulation of cellular calcium levels and normal protein folding. Somatic, or non-inherited, DNA mutations in the CALR gene (mutCALR) can result in abnormal protein function and lead to the development of myeloproliferative neoplasms (MPNs),1 a closely related group of clonal blood cancers in which the bone marrow functions abnormally, overproducing blood cells.2,3 In Essential thrombocythemia (ET) and myelofibrosis (MF), CALR mutations occur in ~25-35% of patients.1,2

Incyte is at the forefront of developing novel therapies for patients with mutCALR ET or MF that target only malignant cells, sparing normal cells, including INCA033989, a first-in-class, mutCALR-specific therapy.

(Press release, Incyte, DEC 7, 2025, View Source [SID1234661225])

On December 7, 2025 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics ("Molecular Partners" or the "Company"), reported it will present updated data from a Phase 1/2a trial of the multispecific T-cell engager MP0533 in patients with acute myeloid leukemia (AML) in a poster at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, taking place December 6-9, 2025, in Orlando, Florida.

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The poster outlines the latest results of this multicenter, open-label study evaluating MP0533 for the treatment of patients with relapsed/refractory (R/R) AML and myelodysplastic syndrome (MDS)/AML (ClinicalTrials.gov: NCT05673057). Data from cohorts 8 and 9 show that densified MP0533 dosing appears tolerable and leads to markedly improved serum exposure in treatment cycle 1, with encouraging preliminary antitumor activity.

"The results in patients with higher frequency dosing regimens of MP0533 are very encouraging. I am happy to see the clinical benefit of MP0533 in a mutation-agnostic manner in R/R AML patients, in particular those with lower disease burden. The data indicate that MP0533 has the potential to significantly improve treatment options for patients with AML and I support investigating MP0533 in a Phase 2 setting to confirm its safety and activity in earlier lines as consolidation addition to existing backbones," said Prof. Courtney DiNardo, M.D., Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, and co-chair of the MP0533 dose escalation review committee (DERC).

As of the data cut-off of September 1, 2025, 54 patients had been treated with MP0533. Eight of 48 evaluable patients achieved a response, with five reaching composite complete responses (3 complete responses, CR, and 2 CR with partial hemotologic recovery) and three reaching morphologic leukemia-free state (MLFS). Six of the 8 responders, and 11 of 14 patients who achieved a reduction in bone marrow blasts of more than 50%, presented with less than 20% bone marrow blast at baseline, indicating that patients with low disease burden are most likely to benefit from MP0533. One patient in cohort 8 has been in complete remission for over a year, and one patient in cohort 9 is on the trial since 4 months. Cohort 10, which aims at reaching the same target dose as cohort 8 while exposing patients to more drug over time, is ongoing with data expected in 2026.

"The Phase 1/2a trial with MP0533 is making good progress, with the densified dosing regimen showing to be feasible, with an acceptable safety profile, and resulting in clinical benefit. The results warrant further exploration of MP0533’s potential, both in the R/R and front-line AML settings in combination with standard of care, and several consortia have approached us expressing interest in conducting such studies. We are actively engaging with potential partners and continue our dialogue with key opinion leaders and regulators to shape the next phase of development of our innovative T-cell engager for patients," said Philippe Legenne, M.D., CMO of Molecular Partners.

MP0533 is a novel tetra-specific T cell-engaging DARPin designed for selective and broad killing of AML cells in a mutation-agnostic manner. MP0533 simultaneously targets three tumor-associated antigens CD33, CD123, and CD70 on AML cells as well as the immune activator CD3 on T cells. AML cells commonly co-express at least two of the three target antigens, whereas most healthy cells only express one or none. MP0533 binds with increasing avidity as the number of its target antigens present increases, thereby preferentially binding to AML cells over healthy cells. This unique mode of action is designed to enable T cell-mediated killing of AML cells while preserving a therapeutic window that minimizes damage to healthy cells.

Details of the poster presentation:

Title: Phase 1/2 study of MP0533, a tetra-specific T-cell engager (CD33 x CD123 x CD70 x CD3), in patients with relapsed/refractory AML or MDS/AML: Initial results from optimized treatment regimen including densified MP0533 dosing and adapted premedication
Session Name: 616. Acute Myeloid Leukemias: Investigational Drug and Cellular Therapies: Poster II
Session Date: December 7, 2025
Presentation Time & Location: 6:00– 8:00 PM ET; OCCC, West Halls B3–B4
Publication Number: 3419

(Press release, Molecular Partners, DEC 7, 2025, View Source [SID1234661213])

On December 7, 2025 Kite, a Gilead Company (Nasdaq: GILD), reported a new analysis demonstrating that second-line Yescarta (axicabtagene ciloleucel) therapy offers consistent benefits in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL), even among those ineligible for the previous standard of care, high-dose chemotherapy followed by an autologous stem cell transplant (ASCT).

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Results were shared from the combined analysis of four-year data from the landmark ZUMA-7 Phase 3 pivotal study of Yescarta for R/R LBCL and two-year data from the Phase 2 ALYCANTE study, designed by French collaborative group LYSA and sponsored by LYSARC, for transplant-ineligible patients. The findings were presented (Abstract #3714) during the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

"Patients with large B-cell lymphoma who are ineligible for stem cell transplants face limited treatment options and poor outcomes due to age, co-morbidities and other factors," said Professor Roch Houot, Head of Haematology Department, University Hospital of Rennes, France and coordinator of the ALYCANTE study. "This analysis reinforces that Yescarta should be considered earlier in a patient’s treatment paradigm given its curative potential as a one-time treatment and further establishes CAR T as the new standard of care for second-line treatment of large B-cell lymphoma."

The efficacy analyses included 178 and 69 patients from the ZUMA-7 and ALYCANTE trials, respectively.

After two years:

Overall survival (OS) rate, meaning the percentage of patients in the trials who were still alive, was 64.9% in the pooled analysis, 62.8% in ZUMA-7, and 70.8% in ALYCANTE. Historically, the prognosis for R/R LBCL was very poor; prior to the introduction of new therapies like CAR Ts, the two-year survival rate was only about 20%.
Event-free survival (EFS) rate, meaning the percentage of patients who were still alive and had not seen their disease worsen or experienced other major complications, was 45.2% in the pooled analysis, 45.4% in ZUMA-7, and 44.7% in ALYCANTE.
Progression-free survival (PFS) rate, meaning the percentage of patients who were still living without their disease getting worse, was 47.4% in the pooled analysis, 47.6% in ZUMA-7, and 46.8% in ALYCANTE.
Additionally:

After three months, 55.6% of the patients in the pooled analysis showed a complete metabolic response (CMR), meaning their disease was barely, if at all, detectable. CMR was 51.2% in ZUMA-7 and 67.7% in ALYCANTE.
After one year after treatment, overall response rate (ORR), meaning patients saw their cancer significantly shrink or completely disappear, was 46.6% in the pooled analysis, 46.5% in ZUMA-7, and 46.8% in ALYCANTE.
For those patients who responded well to treatment, 61% saw that positive response continue after a full year. Pooled 12-month duration of response (DOR) was 61.0%, 60.6% in ZUMA-7, and 62.1% in ALYCANTE.
In the safety analysis, which included 170 ZUMA-7 and 62 ALYCANTE Yescarta-infused patients, safety outcomes were comparable between the two studies. The incidence of grade ≥3 treatment-emergent adverse events (TEAEs) was similar between the ZUMA-7 and ALYCANTE patients, 91.2% and 88.7% respectively, with a pooled incidence of 90.5%. Pooled incidence of grade ≥3 neurologic events, neutropenias, and anemia were 19.8% (ZUMA-7 21.2%, ALYCANTE 16.1%), 64.7% (ZUMA-7 70.0%, ALYCANTE 50.0%), and 27.6% (ZUMA-7 30.0%, ALYCANTE 21.0%), respectively.

Across both studies, patients generally experienced similar long-term improvements in their quality of life after initial treatment challenges. At Day 50 after treatment, patients in both trials showed a transient decline (-7.2 in ZUMA-7 and -6.3 in ALYCANTE) for EORTC QLQ-C30 global health status, and -12.9 for physical function in both. However, patients in ALYCANTE reported a meaningful improvement in their overall well-being (EQ-5D-5L VAS) by Day 100 (+9.9), while ZUMA-7 patients reached a similar meaningful improvement (+9.9) at Day 150, which continued through Month 12. By month 24, both ALYCANTE and ZUMA-7 showed continued improvements of global health status.

"This analysis offers compelling evidence of Yescarta’s consistent, durable efficacy and safety profile across a broad range of patients, including those with difficult-to-treat relapsed or refractory disease who historically faced very limited options and a poor prognosis," said Gallia Levy, MD, PhD, Senior Vice President and Global Head of Development, Kite. "These robust data further reinforce Yescarta’s potential as a treatment with curative intent, reflecting Kite’s deep commitment to transforming patient outcomes."

About LBCL

Globally, LBCL is the most common type of non-Hodgkin lymphoma. In the United States, more than 18,000 people are diagnosed with LBCL each year. About 30-40% of patients with LBCL will need second-line treatment, as their cancer will either relapse (return) or become refractory (not respond) to initial treatment.

About ALYCANTE Study

ALYCANTE (NCT04531046) is a Phase 2 study evaluating the efficacy and safety of Yescarta in patients with R/R LBCL after one prior line of therapy who were deemed ineligible for high-dose chemotherapy and ASCT, sponsored by the LYSA/LYSARC collaborative group. The primary endpoint was the complete metabolic response at three months from Yescarta infusion. The study was funded by Kite, a Gilead Company, and carried out with Yescarta manufactured by Kite.

About LYSA and LYSARC

The Lymphoma Study Association (LYSA) is an independent, multidisciplinary network and an international leader in clinical lymphoma and CLL/WM research. With over 500 experts and a network of 90 centers across France, Belgium, and Portugal, it conducts clinical trials ranging from early-stage treatment evaluation to the development of new therapeutic strategies.

The Lymphoma Academic Research Organization (LYSARC), based in France, is the largest European academic organization dedicated to clinical lymphoma and CLL/WM research. As the operational arm of LYSA, LYSARC sponsors and leads research initiatives and operates specialized platforms in pathology, biology, and imaging. It manages and coordinates numerous clinical trials (phases 1 to 4) each year, as well as non-interventional and data reuse studies. LYSARC is a key research expert, leading innovative projects on an international scale.

About ZUMA-7 Study

Based on the primary efficacy endpoint results of ZUMA-7, the U.S. Food & Drug Administration approved Yescarta as initial treatment of R/R LBCL in April 2022. The EU granted approval in October 2022, followed by approvals in several other countries including Australia, Canada, Great Britain, Israel, Japan and Switzerland.

ZUMA-7 is a randomized, open-label, global, multicenter, Phase 3 study evaluating the safety and efficacy of Yescarta versus standard of care (SOC) for second-line therapy in adult patients with relapsed or refractory LBCL within 12 months of first-line therapy. The SOC for initial treatment of R/R LBCL has been a multi-step process involving platinum-based salvage combination chemotherapy regimen, and for responders, HDT and ASCT. In the study, 359 patients in 77 centers around the world were randomized (1:1) to receive a single infusion of Yescarta or SOC second-line treatment. The primary endpoint was EFS as determined by blinded central review and defined as the time from randomization to the earliest date of disease progression per Lugano Classification, commencement of new lymphoma therapy, or death from any cause. Key secondary endpoints include objective response rate and OS. Additional secondary endpoints included patient-reported outcomes (PROs) and safety. Per hierarchical testing of primary and key secondary endpoints and group sequential testing of OS, an interim analysis of OS occurred at the time of the primary EFS.

About Yescarta

Please see full Prescribing Information, including BOXED WARNING below and Medication Guide.

YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:

Adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy.
Adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
Limitations of Use: YESCARTA is not indicated for the treatment of patients with primary central nervous system lymphoma.

U.S. IMPORTANT SAFETY INFORMATION

BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, and SECONDARY HEMATOLOGICAL MALIGNANCIES

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving YESCARTA. Do not administer YESCARTA to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving YESCARTA, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with YESCARTA. Provide supportive care and/or corticosteroids, as needed.
T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including YESCARTA.
CYTOKINE RELEASE SYNDROME (CRS)

CRS, including fatal or life-threatening reactions, occurred following treatment with YESCARTA. CRS occurred in 90% (379/422) of patients with non-Hodgkin lymphoma (NHL), including ≥ Grade 3 CRS in 9%. CRS occurred in 93% (256/276) of patients with large B-cell lymphoma (LBCL), including ≥ Grade 3 in 9%. Among patients with LBCL who died after receiving YESCARTA, 4 had ongoing CRS events at the time of death. For patients with LBCL in ZUMA-1, the median time to onset of CRS was 2 days following infusion (range: 1-12 days) and the median duration was 7 days (range: 2-58 days). For patients with LBCL in ZUMA-7, the median time to onset of CRS was 3 days following infusion (range: 1-10 days) and the median duration was 7 days (range: 2-43 days).

CRS occurred in 84% (123/146) of patients with indolent non-Hodgkin lymphoma (iNHL) in ZUMA-5, including ≥ Grade 3 CRS in 8%. Among patients with iNHL who died after receiving YESCARTA, 1 patient had an ongoing CRS event at the time of death. The median time to onset of CRS was 4 days (range: 1-20 days) and median duration was 6 days (range: 1-27 days) for patients with iNHL.

Key manifestations of CRS (≥ 10%) in all patients combined included fever (85%), hypotension (40%), tachycardia (32%), chills (22%), hypoxia (20%), headache (15%), and fatigue (12%). Serious events that may be associated with CRS include, cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), renal insufficiency, cardiac failure, respiratory failure, cardiac arrest, capillary leak syndrome, multi-organ failure, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).

The impact of tocilizumab and/or corticosteroids on the incidence and severity of CRS was assessed in 2 subsequent cohorts of LBCL patients in ZUMA-1. Among patients who received tocilizumab and/or corticosteroids for ongoing Grade 1 events, CRS occurred in 93% (38/41), including 2% (1/41) with Grade 3 CRS; no patients experienced a Grade 4 or 5 event. The median time to onset of CRS was 2 days (range: 1-8 days) and the median duration of CRS was 7 days (range: 2-16 days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3 days beginning on the day of infusion of YESCARTA. Thirty-one of the 39 patients (79%) developed CRS and were managed with tocilizumab and/or therapeutic doses of corticosteroids with no patients developing ≥ Grade 3 CRS. The median time to onset of CRS was 5 days (range: 1-15 days) and the median duration of CRS was 4 days (range: 1-10 days). Although there is no known mechanistic explanation, consider the risk and benefits of prophylactic corticosteroids in the context of pre-existing comorbidities for the individual patient and the potential for the risk of Grade 4 and prolonged neurologic toxicities.

Confirm that 2 doses of tocilizumab are available prior to infusion of YESCARTA. Monitor patients at least daily for 7 days following infusion for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for 2 weeks after infusion. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated.

NEUROLOGIC TOXICITIES

Neurologic toxicities including immune effector cell-associated neurotoxicity syndrome (ICANS) that were fatal or life-threatening occurred following treatment with YESCARTA. Neurologic toxicities occurred in 78% (330/422) of patients with NHL receiving YESCARTA, including ≥ Grade 3 in 25%.

Neurologic toxicities occurred in 87% (94/108) of patients with LBCL in ZUMA-1, including ≥ Grade 3 in 31% and in 74% (124/168) of patients in ZUMA-7 including ≥ Grade 3 in 25%. The median time to onset was 4 days (range: 1-43 days) and the median duration was 17 days for patients with LBCL in ZUMA-1. The median time to onset for neurologic toxicity was 5 days (range: 1-133 days) and median duration was 15 days in patients with LBCL in ZUMA-7. Neurologic toxicities occurred in 77% (112/146) of patients with iNHL, including ≥ Grade 3 in 21%. The median time to onset was 6 days (range: 1-79 days) and the median duration was 16 days. Ninety-eight percent of all neurologic toxicities in patients with LBCL and 99% of all neurologic toxicities in patients with iNHL occurred within the first 8 weeks of YESCARTA infusion. Neurologic toxicities occurred within the first 7 days of infusion in 87% of affected patients with LBCL and 74% of affected patients with iNHL.

The most common neurologic toxicities (≥ 10%) in all patients combined included encephalopathy (50%), headache (43%), tremor (29%), dizziness (21%), aphasia (17%), delirium (15%), and insomnia (10%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events, including aphasia, leukoencephalopathy, dysarthria, lethargy, and seizures occurred. Fatal and serious cases of cerebral edema and encephalopathy, including late-onset encephalopathy, have occurred.

The impact of tocilizumab and/or corticosteroids on the incidence and severity of neurologic toxicities was assessed in 2 subsequent cohorts of LBCL patients in ZUMA-1. Among patients who received corticosteroids at the onset of Grade 1 toxicities, neurologic toxicities occurred in 78% (32/41) and 20% (8/41) had Grade 3 neurologic toxicities; no patients experienced a Grade 4 or 5 event. The median time to onset of neurologic toxicities was 6 days (range: 1-93 days) with a median duration of 8 days (range: 1-144 days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3 days beginning on the day of infusion of YESCARTA. Of those patients, 85% (33/39) developed neurologic toxicities; 8% (3/39) developed Grade 3 and 5% (2/39) developed Grade 4 neurologic toxicities. The median time to onset of neurologic toxicities was 6 days (range: 1-274 days) with a median duration of 12 days (range: 1-107 days). Prophylactic corticosteroids for management of CRS and neurologic toxicities may result in higher grade of neurologic toxicities or prolongation of neurologic toxicities, delay the onset, and decrease the duration of CRS.

Monitor patients for signs and symptoms of neurologic toxicities following infusion at least daily for 7 days; and for 2 weeks thereafter and treat promptly. Advise patients to avoid driving for at least 2 weeks following infusion.

HYPERSENSITIVITY REACTIONS

Allergic reactions may occur with the infusion of YESCARTA. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO) or residual gentamicin in YESCARTA.

SERIOUS INFECTIONS

Severe or life-threatening infections occurred after YESCARTA infusion. Infections (all grades) occurred in 45% of patients with NHL. Grade 3 or higher infections occurred in 17% of patients, including ≥ Grade 3 infections with an unspecified pathogen in 12%, bacterial infections in 5%, viral infections in 3%, and fungal infections in 1%. YESCARTA should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after infusion and treat appropriately. Administer prophylactic antimicrobials according to local guidelines.

Febrile neutropenia was observed in 36% of patients with NHL and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as medically indicated.

In immunosuppressed patients, including those who have received YESCARTA, life-threatening and fatal opportunistic infections including disseminated fungal infections (e.g., candida sepsis and aspergillus infections) and viral reactivation (e.g., human herpes virus-6 [HHV-6] encephalitis and JC virus progressive multifocal leukoencephalopathy [PML]) have been reported. The possibility of HHV-6 encephalitis and PML should be considered in immunosuppressed patients with neurologic events and appropriate diagnostic evaluations should be performed.

Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, has occurred in patients treated with drugs directed against B cells, including YESCARTA. Perform screening for HBV, HCV, and HIV and management in accordance with clinical guidelines before collection of cells for manufacturing.

PROLONGED CYTOPENIAS

Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and YESCARTA infusion. Grade 3 or higher cytopenias not resolved by Day 30 following YESCARTA infusion occurred in 39% of all patients with NHL and included neutropenia (33%), thrombocytopenia (13%), and anemia (8%). Monitor blood counts after infusion.

HYPOGAMMAGLOBULINEMIA

B-cell aplasia and hypogammaglobulinemia can occur in patients receiving YESCARTA. Hypogammaglobulinemia was reported as an adverse reaction in 14% of all patients with NHL. Monitor immunoglobulin levels after treatment and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement.

The safety of immunization with live viral vaccines during or following YESCARTA treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during YESCARTA treatment, and until immune recovery following treatment.

SECONDARY MALIGNANCIES

Patients treated with YESCARTA may develop secondary malignancies. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including YESCARTA. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes.

Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing.

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥ 20%) in:

patients with LBCL in ZUMA-7 included fever, CRS, fatigue, hypotension, encephalopathy, tachycardia, diarrhea, headache, musculoskeletal pain, nausea, febrile neutropenia, chills, cough, infection with unspecified pathogen, dizziness, tremor, decreased appetite, edema, hypoxia, abdominal pain, aphasia, constipation, and vomiting.
patients with LBCL in ZUMA-1 included CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections with pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias.
Please see full Prescribing Information, including BOXED WARNING and Medication Guide.

(Press release, Gilead Sciences, DEC 7, 2025, View Source [SID1234661214])

On December 7, 2025 Eli Lilly and Company (NYSE: LLY) reported results from the Phase 3 BRUIN CLL-314 clinical trial evaluating Jaypirca (pirtobrutinib), a non-covalent (reversible) Bruton tyrosine kinase (BTK) inhibitor, versus Imbruvica (ibrutinib), a covalent BTK inhibitor, in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who were treatment-naïve or were BTK inhibitor-naïve. Pirtobrutinib met its primary endpoint of non-inferiority on overall response rate (ORR) compared to ibrutinib (87.0% [95% CI, 82.90-90.44] versus 78.5% [95% CI, 73.73-82.85]; p<0.0001) in the intent-to-treat (ITT) population. Pirtobrutinib also had numerically higher ORR rates and, while immature, progression-free survival (PFS) was also trending in favor of pirtobrutinib compared to ibrutinib across all populations, including a 76% reduction in the risk of disease progression or death (HR=0.239 [95% CI, 0.098-0.586]) in treatment-naïve patients, the subgroup with the longest follow-up.

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These data will be highlighted at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition taking place in Orlando, Florida and simultaneously published in the Journal of Clinical Oncology.

"These data from BRUIN CLL-314 are both novel and clinically significant, demonstrating an improved overall response rate and a favorable trend in progression-free survival outcomes with pirtobrutinib compared to ibrutinib across all populations, including treatment-naïve patients where covalent BTK inhibitors are a cornerstone of treatment," said Jennifer A. Woyach, M.D., professor, hematologist-oncologist, and Director of the Division of Hematology at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. "BRUIN CLL-314 is the first randomized study to compare covalent and non-covalent BTK inhibitors and to directly compare any BTK inhibitors in the treatment-naïve setting, offering findings that are important for advancing the field and patient care. These efficacy results, along with pirtobrutinib’s safety profile, offer strong evidence on the role of pirtobrutinib earlier in the treatment course for patients with CLL or SLL."

The BRUIN CLL-314 study enrolled 662 patients who were randomized to receive pirtobrutinib (n=331) or ibrutinib (n=331), with the ITT population consisting of 225 treatment-naïve and 437 relapsed/refractory patients. The efficacy results utilize a June 10, 2025, data cutoff date.

The study achieved its primary endpoint demonstrating that pirtobrutinib was statistically non-inferior to ibrutinib in independent review committee (IRC)-assessed ORR for the ITT population, and results numerically favored pirtobrutinib (87.0% [95% CI, 82.90-90.44] versus 78.5% [95% CI, 73.73-82.85]; nominal p = 0.0035). Additionally, ORR consistently favored pirtobrutinib versus ibrutinib across all populations evaluated, including relapsed/refractory and treatment-naïve, as well as across pre-specified subgroups such as patients with and without 17p deletions, IGHV status and complex karyotype.

PFS, a key secondary endpoint, was not yet mature at this analysis but was trending in favor of pirtobrutinib compared to ibrutinib in the ITT (HR=0.569 [95% CI, 0.388-0.834]), relapsed/refractory (HR=0.729 [95% CI, 0.471-1.128]), and treatment-naïve (HR=0.239 [95% CI, 0.098-0.586]) populations, with a median follow-up of 22.0 months, 18.4 months, and 22.5 months, respectively. Among all subgroups, the largest PFS effect size was observed in the treatment-naïve subgroup, which had the longest follow-up at this data cut, with a 76% reduction in the risk of disease progression or death. A formal PFS analysis testing for superiority is planned at a future analysis. There was no detriment in overall survival (OS) (HR=0.961 [95% CI, 0.55-1.69]) for the ITT population.

The overall safety profile for patients treated with pirtobrutinib in BRUIN CLL-314 was similar to previously reported trials, and the most common treatment-emergent adverse events were similar between arms. Most adverse events (AE) of interest were lower with pirtobrutinib compared to ibrutinib, including atrial fibrillation/flutter (2.4% versus 13.5%) and hypertension (10.6% versus 15.1%). Fewer AE-related dose reductions (7.9% versus 18.2%) and discontinuations (9.4% versus 10.8%) were seen with pirtobrutinib versus ibrutinib.

"We are excited to share these compelling new findings for pirtobrutinib with the scientific community at ASH (Free ASH Whitepaper) and in the Journal of Clinical Oncology," said Jacob Van Naarden, executive vice president and president, Lilly Oncology. "These data build on additional results from the BRUIN development program and the recent FDA approval for pirtobrutinib in the post-covalent BTK inhibitor setting to reinforce the medicine’s potential to deliver meaningful benefit for people living with CLL or SLL across various disease settings."

As part of the Late-Breaking Abstract Session on Dec. 9, Lilly will also share results from the Phase 3 BRUIN CLL-313 study of pirtobrutinib versus chemoimmunotherapy in patients with treatment-naïve CLL/SLL without del(17p). These data were also selected to be highlighted as part of the ASH (Free ASH Whitepaper) Annual Meeting press program session on Dec. 8.

Lilly is studying Jaypirca in CLL/SLL in multiple Phase 3 studies. Details on the trials can be found by visiting clinicaltrials.gov.

About BRUIN CLL-314
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 planned to enroll 650 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).

About Jaypirca (pirtobrutinib)
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 (reversible) 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.

About Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are forms of slow-growing non-Hodgkin lymphoma that develop from white blood cells known as lymphocytes.4 CLL is one of the most common types of leukemia in adults.4 In the U.S., CLL accounts for about one-quarter of the new cases of leukemia and there will be approximately 23,690 new cases of CLL diagnosed this year.4,5 SLL is identical to CLL from a pathologic and immunophenotypic standpoint, with the main difference between them being the location of the cancer cells.4 In CLL, the cancer cells are present in the blood, and in SLL, the cancer cells are found in the lymph nodes.4

INDICATIONS FOR JAYPIRCA (pirtobrutinib)
Jaypirca is indicated for the treatment of

Adult patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have previously been treated with a covalent BTK inhibitor.
Adult patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical trial benefit in a confirmatory trial.
IMPORTANT SAFETY INFORMATION FOR JAYPIRCA (pirtobrutinib)

Infections: Fatal and serious infections (including bacterial, viral, fungal) and opportunistic infections occurred in Jaypirca-treated patients. Across clinical trials, Grade ≥3 infections occurred (25%), most commonly pneumonia (20%); fatal infections (5%), sepsis (6%), and febrile neutropenia (3.8%) occurred. In patients with CLL/SLL, Grade ≥3 infections occurred (32%), with fatal infections occurring in 8%. Opportunistic infections included Pneumocystis jirovecii pneumonia and fungal infection. Consider prophylaxis, including vaccinations and antimicrobial prophylaxis, in patients at increased risk for infection, including opportunistic infections. Monitor for signs and symptoms, evaluate, and treat. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Hemorrhage: Fatal and serious hemorrhage has occurred with Jaypirca. Across clinical trials, major hemorrhage (Grade ≥3 bleeding or any central nervous system bleeding) occurred (2.6%), including gastrointestinal hemorrhage; fatal hemorrhage occurred (0.3%). Bleeding of any grade, excluding bruising and petechiae, occurred (16%). Major hemorrhage occurred when taking Jaypirca with (2.0%) and without (0.6%) antithrombotic agents. Consider risks/benefits of co-administering antithrombotic agents with Jaypirca. Monitor for signs of bleeding. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca. Consider withholding Jaypirca 3-7 days pre- and post-surgery based on surgery type and bleeding risk.

Cytopenias: Jaypirca can cause cytopenias, including neutropenia, thrombocytopenia, and anemia. Across clinical trials, Grade 3 or 4 cytopenias, including decreased neutrophils (27%), decreased platelets (13%), and decreased hemoglobin (11%), developed. Grade 4 decreased neutrophils (15%) and Grade 4 decreased platelets (6%) developed. Monitor complete blood counts regularly. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Cardiac Arrhythmias: Cardiac arrhythmias occurred in patients taking Jaypirca. Across clinical trials, atrial fibrillation or flutter were reported in 3.4% of Jaypirca treated patients, with Grade 3 or 4 atrial fibrillation or flutter in 1.6%. Other serious cardiac arrhythmias such as supraventricular tachycardia and cardiac arrest occurred (0.4%). Cardiac risk factors such as hypertension or previous arrhythmias may increase risk. Monitor and manage signs and symptoms of arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea). Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Second Primary Malignancies: Across clinical trials, second primary malignancies, including non-skin carcinomas, developed in 9% of Jaypirca-treated patients, most frequently non-melanoma skin cancer (4.4%). Other second primary malignancies included solid tumors (including genitourinary and breast cancers) and melanoma. Advise patients to use sun protection and monitor for development of second primary malignancies.

Hepatotoxicity, Including Drug-Induced Liver Injury (DILI): Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of DILI, has occurred in patients treated with BTK inhibitors, including Jaypirca. Evaluate bilirubin and transaminases at baseline and throughout Jaypirca treatment. For patients who develop abnormal liver tests after Jaypirca, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold Jaypirca. If DILI is confirmed, discontinue Jaypirca.

Embryo-Fetal Toxicity: Jaypirca can cause fetal harm. Administration of pirtobrutinib to pregnant rats caused embryo-fetal toxicity, including embryo-fetal mortality and malformations at maternal exposures (AUC) approximately 3-times the recommended 200 mg/day dose. Advise pregnant women of fetal risk and females of reproductive potential to use effective contraception during treatment and for one week after last dose.

Adverse Reactions (ARs) in Patients Who Received Jaypirca

The most common (≥30%) ARs in the pooled safety population of patients with hematologic malignancies (n=704) were decreased neutrophil count (54%), decreased hemoglobin (43%), decreased leukocytes (32%), fatigue (31%), decreased platelets (31%), decreased lymphocyte count (31%), calcium decreased (30%).

Mantle Cell Lymphoma

Serious ARs occurred in 38% of patients, with pneumonia (14%), COVID-19 (4.7%), musculoskeletal pain (3.9%), hemorrhage (2.3%), pleural effusion (2.3%), and sepsis (2.3%) occurring in ≥2% of patients. Fatal ARs within 28 days of last dose occurred in 7% of patients, most commonly due to infections (4.7%), including COVID-19 (3.1% of all patients).

Dose Modifications and Discontinuations Due to ARs: Dose reductions in 4.7%, treatment interruption in 32%, and permanent discontinuation of Jaypirca in 9% of patients. Permanent discontinuation in >1% of patients included pneumonia.

Most common ARs (≥15%) and Select Laboratory Abnormalities (≥10%) (all Grades %; Grade 3-4 %): hemoglobin decreased (42; 9), platelet count decreased (39; 14), neutrophil count decreased (36; 16), lymphocyte count decreased (32; 15), creatinine increased (30; 1.6), fatigue (29; 1.6), musculoskeletal pain (27; 3.9), calcium decreased (19; 1.6), diarrhea (19; -), edema (18; 0.8), dyspnea (17; 2.3), AST increased (17; 1.6), pneumonia (16; 14), bruising (16; -), potassium decreased (13; 1.6), sodium decreased (13; -), lipase increased (12; 4.4), ALT increased (11; 1.6), potassium increased (11; 0.8), alkaline phosphatase increased (11; -). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (10), platelets decreased (7), lymphocytes decreased (6).

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma from Single-Arm and Randomized Controlled Clinical Trials

Serious ARs occurred in 47-56% of patients across clinical trials. Serious ARs in ≥5% of patients in the single-arm trial were pneumonia (18%), COVID-19 (9%), sepsis (7%), febrile neutropenia (7%). Serious ARs in ≥3% of patients in the randomized controlled trial were pneumonia (21%), COVID-19 (5%), sepsis (3.4%). Fatal ARs within 28-30 days of last Jaypirca dose occurred in 8-11% of patients, most commonly due to infections (7-10%), including sepsis (5%), COVID-19 (2.7-5%), and pneumonia (3.4%).

Dose Modifications and Discontinuations Due to ARs: Dose reductions in 3.6-10%, treatment interruption in 42-51%, and permanent discontinuation of Jaypirca in 9-17% of patients. Permanent discontinuation in >1% of patients included second primary malignancy, pneumonia, COVID-19, neutropenia, sepsis, anemia, and cardiac arrythmias.

Most common ARs and Select Laboratory Abnormalities (≥20%) (all Grades %, Grade 3-4 %)–in a randomized controlled trial: neutrophil count decreased (54; 26), hemoglobin decreased (45; 10), platelet count decreased (37; 17), pneumonia (28; 16), ALT increased (25; 1.8), creatinine increased (25; -), calcium decreased (23; 0.9), sodium decreased (22; 0.9), bilirubin increased (21; 0.9), upper respiratory tract infections (21; 0.9); in a single-arm trial: neutrophil count decreased (63; 45), hemoglobin decreased (48; 19), calcium decreased (40; 2.8), fatigue (36; 2.7), bruising (36; -), cough (33; -), musculoskeletal pain (32; 0.9), platelet count decreased (30; 15), sodium decreased (30; -), COVID-19 (28; 7), pneumonia (27; 16), diarrhea (26; -), abdominal pain (25; 2.7), lymphocyte count decreased (23; 8), ALT increased (23; 2.8), AST increased (23; 1.9), creatinine increased (23; -), dyspnea (22; 2.7), hemorrhage (22; 2.7), lipase increased (21; 7), alkaline phosphatase increased (21; -), edema (21; -), nausea (21; -), pyrexia (20; 2.7), headache (20; 0.9). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (23).

Drug Interactions

Strong CYP3A Inhibitors: Concomitant use increased pirtobrutinib systemic exposure, which may increase risk of Jaypirca ARs. Avoid using strong CYP3A inhibitors with Jaypirca. If concomitant use is unavoidable, reduce Jaypirca dose according to approved labeling.

Strong or Moderate CYP3A Inducers: Concomitant use decreased pirtobrutinib systemic exposure, which may reduce Jaypirca efficacy. Avoid using Jaypirca with strong or moderate CYP3A inducers. If concomitant use with moderate CYP3A inducers is unavoidable, increase Jaypirca dose according to approved labeling.

Sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP Substrates: Use with Jaypirca increased their plasma concentrations, which may increase risk of ARs related to these substrates for drugs sensitive to minimal concentration changes. Follow recommendations for these sensitive substrates in their approved labeling.

Use in Specific Populations

Pregnancy and Lactation: Due to potential for Jaypirca to cause fetal harm, verify pregnancy status in females of reproductive potential prior to starting Jaypirca. Presence of pirtobrutinib in human milk is unknown. Advise women to use effective contraception and to not breastfeed while taking Jaypirca and for one week after last dose.

Geriatric Use: In the pooled safety population of patients with hematologic malignancies, patients aged ≥65 years experienced higher rates of Grade ≥3 ARs and serious ARs compared to patients <65 years of age.

Renal Impairment: Because severe renal impairment increases pirtobrutinib exposure, reduce Jaypirca dose in these patients according to approved labeling.

PT HCP ISI MCL_CLL Q42025

Please see Prescribing Information and Patient Information for Jaypirca.

On December 7, 2025 BeOne Medicines Ltd. (Nasdaq: ONC; HKEX: 06160; SSE: 688235), a global oncology company, reported new data on sonrotoclax, a next-generation investigational BCL2 inhibitor, demonstrating meaningful clinical benefit as monotherapy and in combination across B-cell malignancies. These data were featured at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in Orlando, Florida. The five presentations highlight durable responses in heavily pretreated patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) and additional studies showing deep, rapid, and sustained undetectable minimal residual disease (uMRD) rates with sonrotoclax-based combinations in patients with treatment-naive chronic lymphocytic leukemia (CLL), highlighting the foundational potential of this medicine.

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"The data we’re presenting at ASH (Free ASH Whitepaper) 2025 are redefining what physicians can expect from sonrotoclax as a next-generation BCL2 inhibitor," said Amit Agarwal, M.D., Ph.D., Chief Medical Officer, Hematology, BeOne. "Our data demonstrates that sonrotoclax has succeeded where others have failed, achieving deep and durable responses as a monotherapy in both R/R CLL and MCL and notably fast kinetics as a combination therapy in treatment-naïve CLL. With these results, we believe sonrotoclax will become a foundational medicine in B-cell malignancies, potentially transforming outcomes for patients worldwide."

Sonrotoclax could become the first BCL2 inhibitor indicated for R/R MCL in the U.S., based on data showing an overall response rate (ORR) of 52.4%. (Oral Presentation: 663; December 7 from 5:00-5:15 PM EST)

In this Phase 1/2, global, multicenter, single-arm, open-label study (NCT05471843), ORR by IRC was 52.4% (95% CI, 42.4-62.4) with a complete response (CR) rate of 15.5% (95% CI, 9.1-24.0) in patients with R/R MCL post-treatment with anti-CD20 therapy and a BTK inhibitor treated with 320 mg of sonrotoclax (n=103). Notably, ORR by IRC benefit was consistent across patients with high-risk disease subtypes, including patients with TP53 mutation, a key prognostic marker for MCL. In this patient group, ORR by IRC was 59.1% (95% CI, 36.3-79.3).

At a median study follow-up of 14.2 months (range, 0.3-24.9 months), the median duration of response (DOR) by IRC was 15.8 months (95% CI, 7.4 months-NE) and has yet to reach full maturity. The median time to response (TTR) was 1.9 months (range 1.6-6.5 months), and the median progression-free survival (PFS) was 6.5 months (95% CI: 4.0-10.4).

Treatment with sonrotoclax monotherapy was generally well tolerated, and adverse events were manageable. The most common grade ≥3 treatment-emergent adverse events (TEAEs) in greater than 10% of patients were neutropenia (19.1%), infections (16.5%), and pneumonia (10.4%).

These data are under Priority Review by the U.S Food and Drug Administration for potential accelerated approval.

"Achieving deep and durable responses in relapsed or refractory mantle cell lymphoma after BTK inhibitor therapy has been a long-standing challenge," said Michael Wang, M.D., Professor, Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, and presenting author of the study. "In this analysis, sonrotoclax monotherapy demonstrated meaningful and lasting responses in heavily pretreated patients, including those with high-risk disease. These findings are highly encouraging and suggest this next-generation BCL2 inhibitor could play a foundational role in improving outcomes for patients with limited treatment options."

Sonrotoclax combinations demonstrate fast responses with unmatched uMRD rates and notably better kinetics than current options

BGB-11417-101 (NCT04277637) is an ongoing, phase 1/1b, dose-escalation/expansion study in patients with B-cell malignancies. Results presented at ASH (Free ASH Whitepaper) showcase data from sonrotoclax combinations in patients with treatment-naive (TN) CLL/SLL. Notable highlights include:

Sonrotoclax plus zanubrutinib (Poster Presentation: 3891)
In 135 efficacy-evaluable patients, ORR was 100%, with CR/CR with incomplete count recovery (CRi) in 55% of the 320-mg cohort. Median TTR was 2.6 months (range, 1.5-10.8 months).
At 48 weeks of combination treatment, the uMRD4 rate in the 320-mg cohort was 91% and uMRD rates continue to increase over time, with 98% of patients achieving uMRD4 by 96 weeks.
Median time from the initiation of the combination to uMRD4 was 4.5 months.
With a median study follow-up of 30.9 months, no progression events have been observed in the 320-mg cohort, including in the 40% of patients (34 patients) who had electively discontinued treatment.
The combination was generally well tolerated, with no TEAEs leading to death, or clinical or laboratory tumor lysis syndrome (TLS).
Sonrotoclax plus obinutuzumab (Oral Presentation: 793)
In the 320 mg efficacy-evaluable cohort (n=30), the ORR was 93%, with CR/CRi in 43% of patients.
The median time from reaching sonrotoclax target dose to uMRD was 2.3 months (range, 1.4-5.6 months) in the 320-mg cohort.
The combination was generally well tolerated, with no sonrotoclax discontinuations or deaths due to TEAEs.
Updated efficacy and safety data will be presented on Monday, December 8, 10:30 AM–10:45 AM EST.
Sonrotoclax plus zanubrutinib and obinutuzumab (Poster Presentation: 3890)
In 15 efficacy-evaluable patients, the ORR was 100%, with a CR/CRi rate of 40%.
Of the MRD-evaluable patients (n=10), 100% achieved uMRD4, discontinued treatment as mandated by the protocol, and remain in remission; 80% of patients achieved uMRD6.
With a median study follow-up of approximately 18.0 months, no PFS events have occurred.
The combination was generally well tolerated, and no deaths or discontinuations of any study drug due to TEAEs were observed.
Sonrotoclax monotherapy achieves an ORR by IRC of 76%, with a CR/CRi of 19%, in patients with R/R CLL/SLL, demonstrating rapid and deep responses (Poster Presentation: 5666)

BGB-11417-202 (NCT05479994) is an open-label, phase 2, and a potential registrational study evaluating the efficacy and safety of sonrotoclax in 100 heavily pretreated patients with R/R CLL/SLL. At a median follow-up of 14.4 months (range, 0.2-27.5 months), primary analysis results show:

Similar ORR and CR responses were seen in patients with unmutated IGHV, del(17p) and/or TP53 mutation, and BTK mutation. Median TTR was 3.7 months (range, 1.3-11.1 months).
The best blood uMRD rate was 49.0% (n=49/100). Median time to blood uMRD4 was 5.8 months (range, 3-12 months).
Sonrotoclax monotherapy was well tolerated, and toxicities were manageable and no clinical TLS occurred.
Updated data from the abstract will be presented on Monday, December 8, 6:00-8:00 PM EST. Additionally, these data are under review by China’s National Medical Products Administration (NMPA) for potential accelerated approval.
For more information about our presence at the 2025 ASH (Free ASH Whitepaper) Annual Meeting and Exposition, please visit our meeting hub: congress.beonemedicines.com.

About Mantle Cell Lymphoma

Mantle cell lymphoma (MCL) is a rare subtype of aggressive B-cell non-Hodgkin lymphoma (NHL)1 that develops in B-cells located in the mantle zone of the lymph nodes. MCL accounts for approximately 5% of all NHL cases globally2, affecting an estimated 28,000 people3. MCL is often diagnosed at advanced stages4 and nearly all MCL patients will eventually develop refractory or relapsed (R/R) disease.5 The five-year survival rate for MCL is approximately 50%, reflecting the urgent need for new therapeutic options.6

About Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is a life-threatening cancer of adults. It is a type of mature B-cell malignancy in which abnormal leukemic B lymphocytes (a type of white blood cells) arise from the bone marrow and flood peripheral blood, bone marrow, and lymphoid tissues.7,8 CLL is the most common type of leukemia in adults, accounting for about one-third of new cases.2,9

About Sonrotoclax (BGB-11417)

Sonrotoclax is a next-generation and potentially best-in-class investigational B-cell lymphoma 2 (BCL2) inhibitor with a unique pharmacokinetic and pharmacodynamic profile. Laboratory studies during early drug development have shown that sonrotoclax is a highly potent and specific BCL2 inhibitor with a short half-life and no drug accumulation. Sonrotoclax has shown promising clinical activity across a range of B-cell malignancies and is in development as a monotherapy and in combination with other therapeutics, including BRUKINSA. Notably, in early clinical trials, sonrotoclax plus BRUKINSA has demonstrated rapid and unprecedented rates of undetectable minimal residual disease (uMRD) in treatment-naïve patients with CLL. To date, more than 2,200 patients have been enrolled across the broad sonrotoclax global development program.

The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation (BTD) for sonrotoclax for the treatment of adult patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL). In addition, the FDA has granted sonrotoclax Fast Track Designation for MCL and Waldenström macroglobulinemia, as well as Orphan Drug Designation for the treatment of adult patients with MCL, WM, multiple myeloma, acute myeloid leukemia, and myelodysplastic syndrome.

The information provided in this press release is intended for a global audience.

(Press release, BeOne Medicines, DEC 7, 2025, View Source [SID1234661215])