RegulationPriority Review (US), Breakthrough Therapy (US), Accelerated Approval (US), Orphan Drug (US), Orphan Drug (EU), Conditional marketing approval (CN)

Structure

Molecular FormulaC26H23N7O2

InChIKeyWDENQIQQYWYTPO-IBGZPJMESA-N

CAS Registry1420477-60-6

165

Clinical Trials associated with Acalabrutinib

NCT06520098 / Not yet recruitingPhase 2IIT

Benefit of Venetoclax Addition ("Benefit VA") in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

People who have chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) are often treated with ibrutinib, acalabrutinib, or zanubrutinib. These are pills that are taken by mouth. This type of pill is called "Bruton Tyrosine Kinase Inhibitor" or BTKi. Another treatment for CLL/SLL is a different pill called venetoclax.
The purpose of this study is to compare continuing the current treatment with BTKi alone, as long as it is working, to another arm of treatment which adds venetoclax to the current treatment (BTKi), for one year. After one year, both pills in this arm of treatment would be stopped and the participants will be closely monitored.

Start Date01 Jan 2025

Sponsor / Collaborator

VA Office of Research and Development

NCT06651970 / Not yet recruitingPhase 4

A Multicentre, Open-label, Randomised Phase IV Study to Investigate Acalabrutinib Monotherapy Compared to Investigator's Choice of Treatment in Adults (> 18 Years) With Chronic Lymphocytic Leukaemia and Moderate to Severe Cardiac Impairment

This will be a global Phase IV, open-label, randomised study to evaluate the safety and tolerability of acalabrutinib (monotherapy, 100 mg orally [po], twice daily [bd]) compared to investigator's choice of treatment, in patients with CLL (TN or R/R) and moderate to severe cardiac impairment. All patients will have cardiac impairment as defined by LVEF of < 50%.
Randomisation will be stratified by LVEF > 40% vs ≤ 40% to stratify for moderate and severe cardiac impairment, which for this study are defined as follows:
Severe cardiac impairment: in those with LVEF ≤ 40% Moderate cardiac impairment: in those with LVEF > 40% to < 50%. The study is planned to take place in approximately 20 centres globally. The study will be conducted in centres that have established close collaboration between the Haematology and Cardiology divisions, preferably with a cardio-oncologist on the team.
An IDMC will be responsible for making recommendations for study continuation.

Start Date31 Dec 2024

Sponsor / Collaborator

AstraZeneca PLC

[+3]

NCT06441097 / Not yet recruitingPhase 2IIT

A Study to Evaluate the Efficacy and Safety of Genotype-guided Targeted Agents in Combination With POLA-RCHP VERSUS POLA-RCHP in Patients With Previously Untreated Diffuse Large B-cell Lymphoma

The purpose of this study is to compare the efficacy and safety of genotype-guided targeted agents in combination with polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola RCHP-X) versus Pola RCHP in Chinese patients with previously untreated diffuse large B-cell lymphoma (DLBCL).

Start Date31 Dec 2024

Sponsor / Collaborator

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

100 Clinical Results associated with Acalabrutinib

100 Translational Medicine associated with Acalabrutinib

100 Patents (Medical) associated with Acalabrutinib

480

Literatures (Medical) associated with Acalabrutinib

31 Dec 2024·JOURNAL OF MEDICAL ECONOMICS

Matching-adjusted indirect comparison of acalabrutinib versus ibrutinib in relapsed/refractory mantle cell lymphoma

Article

Author: Cai, Ling ; Roos, Jack ; Miranda, Paulo A. P. ; Liljas, Bengt ; Wang, Michael ; Rule, Simon

OBJECTIVE:

In the absence of head-to-head clinical trials, matching-adjusted indirect comparison (MAIC) was used to compare two Bruton tyrosine kinase inhibitors (BTKis) approved for the treatment of relapsed/refractory (R/R) mantle cell lymphoma (MCL). This analysis compares the efficacy and safety of acalabrutinib versus ibrutinib using a more mature dataset than a previously published MAIC.

METHODS:

Individual patient data from 122 patients treated with acalabrutinib in a phase 2 study were weighted to match aggregate baseline characteristics of patients pooled from three separate trials of ibrutinib. Patients were matched on Eastern Cooperative Oncology Group performance status, simplified Mantle Cell Lymphoma International Prognostic Index, lactate dehydrogenase, prior lines of therapy, tumor burden, and blastoid histology. Outcomes assessed included progression-free survival (PFS), overall survival (OS), and adverse events.

RESULTS:

After matching, differences in PFS between acalabrutinib (median = 17.8 months) and ibrutinib (median = 12.8 months) were not statistically significant (hazard ratio [HR] = 0.92; 95% confidence interval [CI] = 0.74-1.15; p = 0.48). Similarly, after matching, OS differences between acalabrutinib (median = 36.5 months) and ibrutinib (median = 27.9 months) did not reach statistical significance (HR = 0.87; 95% CI = 0.64-1.17; p = 0.35). Acalabrutinib was associated with an improved safety profile compared with ibrutinib, with statistically significantly lower rates of grade ≥3 atrial fibrillation and thrombocytopenia.

CONCLUSIONS:

This comparison of two BTKis used in the treatment of R/R MCL showed that PFS and OS risk was not statistically different between the treatments; however, acalabrutinib had an improved safety profile compared with ibrutinib.

06 Dec 2024·Hematology-American Society of Hematology Education Program

The evolving frontline management of CLL: are triplets better than doublets? How will we find out?

Review

Author: Rogers, Kerry A. ; Woyach, Jennifer A.

Abstract:

Frontline therapy for chronic lymphocytic leukemia (CLL) has substantially advanced in the previous decade. While monotherapy with a Bruton's tyrosine kinase (BTK) inhibitor is an excellent option for many patients, combination therapies are of high clinical interest as they can induce deep responses and durable remissions, and in many cases allow discontinuation of therapy. There are several doublet therapies that are currently in clinical use. These include combinations of BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib) or BCL2 inhibitors (venetoclax) with anti-CD20 monoclonal antibodies, and combinations of BTK and BCL2 inhibitors. While BTK inhibitors with anti-CD20 monoclonal antibodies still typically require indefinite therapy, combinations involving the BCL2 inhibitor venetoclax have allowed for successful therapy discontinuation. Triplets, which combine all 3 of these paradigms, are of interest especially for patients with higher-risk disease. While triplets have been mainly studied in single-arm trials with excellent outcomes, comparative data to doublets are limited. In this article, we outline the doublet and triplet regimens that have been evaluated in CLL as well as the data from trials comparing doublets and triplets.

02 Dec 2024·JOURNAL OF CLINICAL INVESTIGATION

FoxO1/Rictor axis induces a nongenetic adaptation to ibrutinib via Akt activation in chronic lymphocytic leukemia

Article

Author: Kostalova, Lenka ; Mraz, Marek ; Charalampopoulou, Stella ; Seda, Vaclav ; Vichova, Rachel ; Maiques-Diaz, Alba ; Soucek, Karel ; Panovska, Anna ; Davids, Matthew S ; Doubek, Michael ; Zeni, Pedro Faria ; Chiodin, Giorgia ; Pavelkova, Petra ; Filip, Daniel ; Ondrisova, Laura ; Forconi, Francesco ; Brown, Jennifer R ; Martin-Subero, Jose I ; Mayer, Jiri ; Mladonicka Pavlasova, Gabriela ; Vecera, Josef ; Oppelt, Jan ; Lysak, Daniel ; Davids, Matthew S. ; Martin-Subero, Jose I. ; Kahounova, Zuzana ; Simkovic, Martin ; Vrbacky, Filip ; Fernandes, Stacey M. ; Hlavac, Krystof ; Brown, Jennifer R. ; Hoferkova, Eva ; Fernandes, Stacey M ; Plevova, Karla ; Pospisilova, Sarka

Bruton tyrosine kinase (BTK) inhibitor therapy induces peripheral blood lymphocytosis in chronic lymphocytic leukemia (CLL), which lasts for several months. It remains unclear whether nongenetic adaptation mechanisms exist, allowing CLL cells' survival during BTK inhibitor-induced lymphocytosis and/or playing a role in therapy resistance. We show that in approximately 70% of CLL cases, ibrutinib treatment in vivo increases Akt activity above pretherapy levels within several weeks, leading to compensatory CLL cell survival and a more prominent lymphocytosis on therapy. Ibrutinib-induced Akt phosphorylation (pAktS473) is caused by the upregulation of Forkhead box protein O1 (FoxO1) transcription factor, which induces expression of Rictor, an assembly protein for the mTORC2 protein complex that directly phosphorylates Akt at serine 473 (S473). Knockout or inhibition of FoxO1 or Rictor led to a dramatic decrease in Akt phosphorylation and growth disadvantage for malignant B cells in the presence of ibrutinib (or PI3K inhibitor idelalisib) in vitro and in vivo. The FoxO1/Rictor/pAktS473 axis represents an early nongenetic adaptation to B cell receptor (BCR) inhibitor therapy not requiring PI3Kδ or BTK kinase activity. We further demonstrate that FoxO1 can be targeted therapeutically and its inhibition induces CLL cells' apoptosis alone or in combination with BTK inhibitors (ibrutinib, acalabrutinib, pirtobrutinib) and blocks their proliferation triggered by T cell factors (CD40L, IL-4, and IL-21).

132

News (Medical) associated with Acalabrutinib

15 Dec 2024

·www.prnewswire.com

Innovent and Lilly Expand Collaboration Through Agreement on Commercialization Rights for Jaypirca® (pirtobrutinib) in Mainland China

SAN FRANCISCO and SUZHOU, China, Dec. 15, 2024 /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 diseases, and Eli Lilly and Company (NYSE: LLY) today jointly announced a Distribution and Promotion Agreement in Mainland China regarding Lilly's non-covalent (reversible) Bruton's tyrosine kinase (BTK) inhibitor, Jaypirca® (pirtobrutinib, 100 mg & 50 mg tablets). The agreement highlights the following aspects: Innovent will be responsible for the importation, marketing, distribution and promotion of Jaypirca®; Lilly will be responsible for the R&D and post-market medical affairs of Jaypirca®. Jaypirca®, a highly selective kinase inhibitor, utilizes a novel non-covalent binding mechanism to re-establish BTK inhibition in mantle cell lymphoma (MCL) patients previously treated with a covalent BTK inhibitor (approved including ibrutinib, acalabrutinib, zanubrutinib, or orelabrutinib) and extend the benefit of targeting the BTK pathway, thus effectively addressing the unmet clinical needs for these patients. Approved by the U.S. FDA in January 2023, Jaypirca® (pirtobrutinib) became the first and only approved non-covalent (reversible) BTK inhibitor. In October 2024, Jaypirca® (pirtobrutinib) received approval from China's National Medical Products Administration (NMPA) as monotherapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two types of systemic therapy, including a Bruton's tyrosine kinase (BTK) inhibitor (Link). Lilly is conducting comprehensive global Phase 3 development programs (including in China), in first-line and relapse or refractory patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and BTK inhibitor-naïve relapse or refractory MCL, to explore monotherapy or combination therapy. Under the agreement, Innovent holds the sole commercialization rights for Jaypirca® in Mainland China, overseeing importation, marketing, distribution and promotion. Lilly will be responsible for R&D and post-market medical affairs. Leveraging Innovent's established hematology oncology commercial team and Lilly's deep expertise in drug development and scientific insights in the therapeutic area, the partnership is committed to broadening access to innovative treatments and improving outcomes for cancer patients in Mainland China. Dr. Michael Yu, Founder, Chairman and CEO of Innovent, stated: "Building on our long-term strategic collaboration with Lilly, we are proud to expand our collaboration through this agreement. Jaypirca®, the world's first and only approved non-covalent (reversible) BTK inhibitor, represents a breakthrough treatment option for patients who have previously received BTK inhibitors. Innovent has built a robust and leading portfolio in the hematological malignancy field, consisting of TYVYT® (sintilimab injection), HALPRYZA® (rituximab injection), olverembatinib, FUCASO® (Equecabtagene Autoleucel Injection), and Jaypirca®. By fully leveraging our commercialization capabilities and extensive coverage in this field, we aim to bring forward innovative medicines to benefit cancer patients and further enhance our leading position in oncology. We remain steadfast in our commitment to advancing the biopharmaceutical industry through collaborative efforts so that first-rate pharmaceutical drugs can become widely accessible." Huzur Devletsah, President and General Manager of Lilly China, states, "Lilly is thrilled to appoint Innovent for the distribution and promotion of Jaypirca® marking a pivotal moment in hematologic cancer treatment for Lilly. This agreement allows to rapidly increase patient access in Mainland China by drawing on Innovent's robust market presence and our extensive R&D expertise. Together, we are poised to deliver innovative therapies and support the 'Healthy China 2030' initiative, continuing our commitment: 'In China, For China." About Jaypirca® (pirtobrutinib) Jaypirca® (pirtobrutinib, formerly known as LOXO-305) 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.[i] BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including mantle cell lymphoma.[ii],[iii] About Innovent's strategic cooperation with Lilly Innovent and Lilly have established a comprehensive level of cooperation, setting an example of partnership between a Chinese innovative pharmaceutical company and a global leading medicine company in the field of R&D, CMC, clinical development and commercialization, aiming to accelerate the access of innovative medicines to benefit more patients worldwide. In March 2015, Innovent entered into a strategic partnership with Lilly focused on biological medicine. Under the initial agreement, Lilly and Innovent co-developed and co-commercialized oncology medicines, including Tyvyt® (sintilimab injection) in China. In October 2015, the two parties announced the extension of collaboration to include the co-development of three additional antibodies in oncology. In August 2019, the cooperation extended with a licensing agreement for the development and commercialization of a potentially global best-in-class investigational GCG/GLP-1 medicine in China. In August 2020, Innovent and Lilly announced a global expansion of their strategic alliance for sintilimab. In March 2022, Lilly and Innovent deepened their engagement in oncology, granting Innovent sole commercialization rights for Cyramza® (ramucirumab) and Retsevmo® (selpercatinib), and a right of first negotiation for potential future commercialization of Jaypirca® (pirtobrutinib) in Mainland China. In December 2024, the agreement of the commercialization of Jaypirca® (pirtobrutinib) in Mainland China officially achieved. About Innovent Biologics 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 12 products in the market. It has 5 new drug applications under regulatory review, 3 assets in Phase III or pivotal clinical trials and 17 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, Adimab, 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), Selpercatinib (Retsevmo) and Pirtobrutinib (Jaypirca) were developed by Eli Lilly and Company. About Eli Lilly and Company 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 nearly 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. To learn more, visit . 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 Biologics, Inc. ("Innovent" or "Company"), are intended to identify certain of such forward-looking statements. The Company 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 the Company 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 the Company'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, the Company's competitive environment and political, economic, legal and social conditions. The Company, the Directors and the employees of the Company assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect. References SOURCE Innovent Biologics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

License out/inDrug ApprovalPhase 3Biosimilar

10 Dec 2024

·www.biopharmadive.com

ASH24: Leukemia drug sequencing, sickle cell questions and a new kind of CAR-T

The American Society of Hematologys annual meeting continued Monday with important presentations and discussions on the latest blood disease research, several of which weve summarized here.Sequencing BTK inhibitors in leukemiaIn the years since the approval of Imbruvica for chronic lymphocytic leukemia a decade ago, it and other so-called BTK inhibitors have become mainstay treatments for the slow-growing blood cancer. Their adoption has given physicians new options to control the diseases progression, but also new questions around how they might combine and sequence the therapies.This years ASH meeting could give doctors some needed answers, featuring two important studies involving Calquence, a BTK blocker from AstraZeneca, and Jaypirca, a similarly targeted drug from Eli Lilly that works in a slightly different way.Lillys study of Jaypirca is the first randomized Phase 3 trial in CLL thats exclusively enrolled patients who previously were treated with another BTK inhibitor. This was a clinical trial that really represents the patient population that ... has received these modern standards of care over the past few years and now needs something else, said David Hyman, Lillys chief medical officer, in an interview.Results showed Jaypirca nearly doubled the time to disease progression or death compared to investigators choice of two older drug regimens. Jaypirca also substantially lengthened the median time to next treatment or death by 13 months over the control group. Treatment with Lillys drug led to fewer severe side effects, too.According to Jacob Van Naarden, head of Lilly Oncology, the data raise the question of whether physicians might want to try Jaypirca instead of another drug called Venclexta after a patients disease progresses on their first BTK inhibitor. (Venclexta targets a different protein than BTK.)Jaypirca was approved in the U.S. one year ago for adults with CLL who have received at least two lines of prior therapy. Lilly plans to submit this new data to regulators as confirmatory evidence for that accelerated approval.Also at ASH, AstraZeneca presented results from a study combining its drug Calquence with Venclexta in previously untreated CLL patients. The combination reduced the risk of disease progression or death by 35% versus standard chemoimmunotherapy, according to the data. Adding a third, different drug, Gazyva, lowered the risk even further, but at the cost of a higher rate of side effects.With these more recent therapies, people with CLL can live a pretty long time, said Van Naarden. And so the question is:How do you get the most total amount of disease control over the course of the person's life? Do you get more out of using [these drugs] upfront together versus in sequence?Questions, but few answers, on sickle cell drug recallAt many of ASHs recent meetings, attendees have heard of progress in the development of new drugs for sickle cell disease, work that led to four new approved medicines over the past five years.Conference-goers this year had a different sort of news to process. Just over two months ago, Pfizer abruptly withdrew one of those new medicines from markets worldwide, citing new safety concerns that, in its view, meant the drugs benefits no longer outweighed its risks.In particular, emerging data from several studies showed an imbalance in deaths, mostly from malaria infections, among participants on Pfizers drug. Observational testing, meanwhile, found higher rates of sickle cell pain crises after treatment.“I think [Pfizers decision] took many of us many of the people I know by surprise, said John Strouse, a hematologist and sickle cell specialist at Duke University, during a special ASH session on Pfizers withdrawal of its drug, called Oxbryta.Strouse ran a poll of the audience during the session, asking for the reactions doctors and researchers had had. Two-thirds chose surprise, 11% picked angry and 7% anxiety.While there had been signs of growing questions around Oxbrytas safety, Strouse and other speakers at the ASH session noted they had heard little from Pfizer prior to the withdrawal.We need to encourage timely public disclosure of scientific findings to allow for vigorous conversation, said Alexis Thompson, chief of the Childrens Hospital of Pennsylvanias hematology division. I think it's safe to say that didn't happen here.“Strouse recounted some of the difficulties sickle cell physicians encountered in responding to the withdrawal, including figuring out how to stop treatment in patients who were taking Oxbryta. Pfizer hadnt provided any guidance, so doctors were forced to experiment with their own tapering regimens.The reason you had this variation in recommendations, variation in care, is because we really didn't know what the right answer [was], said Strouse.Physicians are still hunting for answers. Maureen Achebe, clinical director of hematology services at Brigham and Women's Hospital and Dana-Farber Cancer Institute, explained during the session how the withdrawal has raised several questions about future sickle cell research. Among them: Are surrogate measures, like increases in hemoglobin, appropriate for regulatory clearance? Should approvals be limited to match the specific patient population involved in testing?CAR-Ts next target in multiple myelomaThe past decade has brought a panoply of new drugs for multiple myeloma, a cancer of the blood and bone marrow. Among the most recent additions are treatments that target a protein found on malignant plasma cells and called GPRC5D for short. One, Johnson & Johnsons bispecific antibody Talvey, has already been approved in the U.S.Other companies are designing cell therapies that target the same protein. At ASH on Monday, Bristol Myers Squibb presented the first survival and cancer progression data for its candidate, a CAR-T treatment its now dubbed arlo-cel.The results are from a Phase 1 study that enrolled people who had received at least three prior drugs for their multiple myeloma. Nearly 90% of the 79 study participants who were evaluable for drug efficacy responded to treatment, and just over a quarter experienced a complete response, or remission. The median time to cancer progression or death was 18 months, while median overall survival was not yet reached.As with all CAR-T therapies, many treated patients experienced an immune reaction known as cytokine release syndrome, which was typically mild in severity. One patient with this side effect died, according to a study abstract. Three patients experienced hemophagocytic lymphohistiocytosis, another dangerous immune reaction, while eight had neurological toxicity.Bristol Myers is testing arlo-cel further in a Phase 2 study called Quintessential. Were excited to disclose the progress of our robust pipeline, with promising early survival results for our GPRC5D-targeted cell therapy underscoring the first-in-class potential of [arlo-cel]for patients with relapsed or refractory multiple myeloma, Bryan Campbell, a Bristol Myers Squibb cell therapy executive, said in a statement,The company, which sells two cell therapies for myeloma and lymphoma, also presented data at ASH for a CD19-targeting CAR-T treatment in people with severe autoimmune diseases. '

Clinical ResultCell TherapyImmunotherapyPhase 3ASH

09 Dec 2024

·endpts.com

BTK inhibitors from AstraZeneca, Eli Lilly and BeiGene take center stage in CLL

SAN DIEGO — Some of the biggest names in BTK inhibitors presented updated datasets at the American Society of Hematology annual meeting this weekend, most notably AstraZeneca and Eli Lilly. AstraZeneca and Eli Lilly outlined how their drugs Calquence and Jaypirca can help patients with chronic lymphocytic leukemia (CLL). Individuals live with CLL chronically, unlike more aggressive cancers like acute lymphoblastic leukemia or multiple myeloma, and if they relapse often have other effective drugs to turn to. In addition, BeiGene reported five-year follow-up data for its drug Brukinsa in first-line CLL. Mehrdad Mobasher, BeiGene’s chief medical officer in hematology, said the follow-up is “one of the most important” updates for Brukinsa at the medical meeting, as it shows sustained efficacy following the drug’s approval in CLL last January. AstraZeneca this weekend expanded on its Phase 3 win from July for fixed-dose Calquence regimens in first-line CLL, combining the drug with AbbVie and Roche’s Venclexta, with or without Roche’s Gazyva. Researchers tested the regimens in 867 patients, randomizing them 1-to-1-to-1 against Rituxan plus chemo. Both regimens met the primary endpoint of progression-free survival, with the triple regimen of Calquence, Venclexta and Gazyva lowering patients’ risk of disease progression or death by 58% and achieving a progression-free survival (PFS) rate of 83.1% after 36 months of treatment. The Calquence and Venclexta combo reported a PFS of 76.5%, reducing disease progression or death by 35%, and the control group achieved a 65.5% PFS rate. Both results were statistically significant. AstraZeneca also conducted analyses that excluded deaths in the trial that were a result of Covid-19, since the company was enrolling patients during the height of the pandemic. When those deaths were excluded, the triple regimen reduced patients’ risk of disease progression or death by 74%, and the double regimen by 29%. Susan Galbraith, AstraZeneca’s EVP of oncology R&D, declined to comment on the company’s regulatory plans. But she told Endpoints News that she doesn’t believe it will be difficult to market the drug since patients and physicians are already familiar with all three therapies. “We have it established with both community oncologists, as well as physicians who are in academic centers,” Galbraith said. “I don’t think it will be difficult to drive uptake of this.” Galbraith added she thinks it will be mostly new CLL patients who end up taking the regimens, rather than those who have been taking Calquence already without Venclexta. Calquence is currently approved in CLL as a monotherapy and in combination with Gazyva. Eli Lilly’s third-generation BTK inhibitor Jaypirca bested investigators’ choice treatments in previously treated CLL and small lymphocytic leukemia (SLL), meeting the primary endpoint in a confirmatory trial. In the Phase 3 BRUIN CLL-321 study, Jaypirca reduced patients’ risk of relapse, disease or death by 46% compared to two regimens consisting of either idelalisib plus rituximab or bendamustine plus rituximab. The drug won accelerated approval last December in patients who’ve been treated with at least two prior therapies, including one other BTK inhibitor and a BCL-2 inhibitor. Lilly Oncology president Jacob Van Naarden said the company will file with the FDA for full approval “soon.” “We almost doubled the progression-free survival in the clinical trial,” chief medical officer David Hyman told Endpoints . At a median follow-up of 19 months, median progression-free survival in the Jaypirca arm was 14 months compared with 8.7 months in the control arm, as assessed by an independent review committee. Van Naarden said this was the first randomized Phase 3 CLL trial in patients who previously received a BTK inhibitor. The results, he said, could potentially make the case for Jaypirca’s use in earlier settings. “In real clinical practice, most patients start with a covalent BTK inhibitor, they eventually relapse. They get a venetoclax-based regimen, they eventually relapse, and then they’re getting pirtobrutinib,” Van Naarden said ahead of Lilly’s data release. “The data we’re presenting tomorrow raise the question of whether or not pirto should be used before venetoclax in certain patients or not.” While there wasn’t a statistically significant difference between the Jaypirca and control arms in overall survival, Van Naarden and Hyman said the data were confounded by high degrees of crossover. Patients in the control arm were allowed to switch to Jaypirca after seeing disease progression, and a majority of them (76%) did. Lilly reported that multiple analyses adjusting for the crossover effect showed trends in favor of Jaypirca. “We never, ever powered or contemplated this study to be designed to demonstrate a survival benefit,” Hyman said. “In CLL, basically all of the things that we do are based on progression-free survival.” BeiGene touted a “deepening of responses” in five-year follow-up data for its BTK inhibitor Brukinsa in CLL or SLL. At a median follow-up of 61.2 months, Brukinsa reduced first-line patients’ risk of disease progression or death by 71% compared to a combination of the cancer drugs bendamustine and Rituxan, BeiGene said at ASH. The results are from the Phase 3 SEQUOIA study, which helped support Brukinsa’s approval in CLL last year. “Efficacy is sustained. Responses are getting deeper,” BeiGene’s Mobasher told Endpoints. “Brukinsa has now proven to be the best-in-class BTK inhibitor.” BeiGene is also studying Brukinsa in combination with its experimental BCL2 inhibitor sonrotoclax. The company reported updated Phase 1/1b results at this year’s ASH suggesting the combination was well-tolerated and achieved a 99% overall response rate in patients with mature B-cell malignancies at a median follow-up of 19.4 months. The Brukinsa sonrotoclax combination is currently in an ongoing fixed-duration Phase 3 study, which started last year and is “enrolling extremely well,” Mobasher said.

Clinical ResultPhase 3ASHDrug Approval

100 Deals associated with Acalabrutinib

External Link

KEGG	Wiki	ATC	Drug Bank
D10893	Acalabrutinib	L01XE51	DB11703

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Small Lymphocytic Lymphoma	US	AstraZeneca UK Ltd.	21 Nov 2019
Chronic Lymphocytic Leukemia	CA	AstraZeneca Canada, Inc.	02 Oct 2019
Mantle-Cell Lymphoma	US	AstraZeneca UK Ltd.	31 Oct 2017

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Large B-cell lymphoma	Phase 3	DE	AstraZeneca PLC	07 Jun 2023
Recurrent Chronic Lymphoid Leukemia	Phase 3	DE	AstraZeneca PLC	19 Apr 2022
Diffuse Large B-Cell Lymphoma	Phase 3	US	AstraZeneca PLC	08 Oct 2020
Diffuse Large B-Cell Lymphoma	Phase 3	CN	AstraZeneca PLC	08 Oct 2020
Diffuse Large B-Cell Lymphoma	Phase 3	JP	AstraZeneca PLC	08 Oct 2020
Diffuse Large B-Cell Lymphoma	Phase 3	AU	AstraZeneca PLC	08 Oct 2020
Diffuse Large B-Cell Lymphoma	Phase 3	AT	AstraZeneca PLC	08 Oct 2020
Diffuse Large B-Cell Lymphoma	Phase 3	BE	AstraZeneca PLC	08 Oct 2020
Diffuse Large B-Cell Lymphoma	Phase 3	BR	AstraZeneca PLC	08 Oct 2020
Diffuse Large B-Cell Lymphoma	Phase 3	CA	AstraZeneca PLC	08 Oct 2020

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03836261 (AMPLIFY, ASH2024) Manual	Phase 3	Chronic Lymphocytic Leukemia First line	867	Acalabrutinib + Venetoclax	hyqpkvuamt(qxhnwthcsa) = curquoyule ambeyrqvws (ropqibfuki ) View more	Positive	09 Dec 2024
				Acalabrutinib + Venetoclax + Obinutuzumab	hyqpkvuamt(qxhnwthcsa) = ffqftbbgtb ambeyrqvws (ropqibfuki ) View more
NCT04462328 (ASH2024) Manual	Phase 1	Primary Central Nervous System Lymphoma	13	Acalabrutinib 100 mg BID + DurvalumabDurvalumab 1500 mg IV	wjgvxbwhov(ybrmghcvjl) = axqedyuphm rqzpswdozr (lknofofgkx ) View more	Positive	09 Dec 2024
ASH2024	Not Applicable	Mantle-Cell Lymphoma	-	Acalabrutinib 100 mg BID + Rituximab 375 mg/m2 IV	pxlzwiimok(rtmmrnvspq) = grade 3-4 AE were cardiovascular toxicity in 7 pts orwauyqnku (axnzouwhzv ) View more	-	09 Dec 2024
ASH2024	Not Applicable	Mantle-Cell Lymphoma	-	Acalabrutinib	vyckarmckz(bofdmynphn) = 16% gokrqwsrcp (bjaozztrbp ) View more	-	09 Dec 2024
				Venetoclax
ASH2024	Not Applicable	Chronic Lymphocytic Leukemia	-	Acalabrutinib 100 mg	pkwgwgblcq(eqbrqvwwto) = AEs leading to death occurred in 1 pt in the acalabrutinib arm (unrelated to study drug) bmnycwssah (ndftwgbdeq ) View more	-	08 Dec 2024
				Chlorambucil+Rituximab
ASH2024	Not Applicable	Diffuse Large B-Cell Lymphoma	-	RICE-A + Acalabrutinib 100mg BID	ozwnrqgzmr(gexrtfdtxu) = Gastrointestinal AEs were observed in 5 patients (4 Grade1/2 and 1 Grade3/4) ushqkwyfzi (dzywmgvtzp ) View more	-	08 Dec 2024
ASH2024	Not Applicable	Chronic Lymphocytic Leukemia	-	Ibrutinib 420 mg/day	zfssescbme(kwwnzbapvn) = 21% for acala vnffsovhqx (xxbygqubzp ) View more	-	08 Dec 2024
				Acalabrutinib 100 mg twice daily
ASH2024	Not Applicable	Mantle-Cell Lymphoma	-	Acalabrutinib (BR/CR)	dvtgctslak(lrwdkszwez) = wkrgimgnmb emsnsumoxb (xoqzpjrvfi ) View more	-	07 Dec 2024
				Acalabrutinib (BR/CR-A)	dvtgctslak(lrwdkszwez) = thtyrwwefs emsnsumoxb (xoqzpjrvfi ) View more
NCT03580928 (AMPLIFY, Pubmed \| J Clin Oncol)	Phase 2	Chronic Lymphocytic Leukemia TP53 aberration	-	Acalabrutinib, Obinutuzumab, Venetoclax	rytoitijaq(jboayuptvt) = kdvomjcbmd jwywgawcpd (efbwmrwvov ) View more	Positive	07 Dec 2024
				Chemoimmunotherapy	rytoitijaq(jboayuptvt) = elcgezicjn jwywgawcpd (efbwmrwvov ) View more
ASH2024	Not Applicable	Chronic Lymphocytic Leukemia	-	Acalabrutinib	jsegabhanv(qptktlmckd) = mijvqdwlhs qzaqzskvst (wcmcpmzvbe ) View more	-	07 Dec 2024
				Obinutuzumab	kewdvofdga(kpnourkqoq) = noqwowbpfo dxcslhzuiz (ifztanewbn ) View more

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis