The ASCO Annual Assembly showcases essentially the most cutting-edge analysis within the area of medical oncology and essentially the most superior superior most cancers remedies. It’s the most influential and well-known scientific occasion within the world medical oncology neighborhood. Ascentage is demonstrating medical growth progress on the ASCO Annual Assembly for the seventh consecutive yr and has chosen to current 4 medical research, together with oral shows, of the corporate’s three proprietary drug candidates on the ASCO 2024 Annual Assembly.
The most recent outcomes from this medical examine validate the favorable security and efficacy of lisaftoclax monotherapy and mixture remedy in WM. Information present that lisaftoclax mixed with ibrutinib confirmed an goal response fee (ORR) of 90.9% in treatment-naïve WM sufferers (response was not affected by the drug) CXCR4 mutations), manageable adversarial occasions (AEs) and low danger of tumor lysis syndrome (TLS). Moreover, no potential drug interactions (DDIs) with ibrutinib have been noticed within the examine.
“Lisaftoclax is a brand new Bcl-2 selective inhibitor designed to deal with malignant tumors by selectively blocking the anti-apoptotic protein Bcl-2, thereby restoring the traditional apoptosis means of most cancers cells,” stated PhD.
“Lisaftoclax is the primary pivotal section Bcl-2 inhibitor
Highlights of the fabric introduced at ASCO 2024 are as follows:
Up to date efficacy and security outcomes of the BCL-2 inhibitor lisaftoclax (APG-2575) alone or together with ibrutinib or rituximab in sufferers (pts) with Waldenstrom’s macroglobulinemia (WM)
Summary#: 7078
Assembly Hematological malignancies Lymphoma and continual lymphocytic leukemia
Date and time: Monday, June 3, 2024, 9:00 am”
First writer: Massa Rasika, MBBS, FRACP, FRCPA, St Vincent’s Hospital Melbourne,
emphasize:
background: Lisaftoclax is a brand new, oral, extremely selective and potent Bcl-2 inhibitor. In an ibrutinib-resistant patient-derived xenograft/preclinical mannequin of WM, lisaftoclax was strongly synergistic when mixed with ibrutinib.
introduce: That is an open-label, multi-center, world Section Ib/II examine designed to guage the efficacy, security, and tolerability of lisaftoclax as monotherapy or together with ibrutinib/rituximab and different medication in sufferers with WM. Receptivity and pharmacokinetics (PK).
Affected person registration and strategies:
- On this examine, WM sufferers have been included in 3 teams, together with Group A: sufferers with resistance or intolerance to earlier remedy with Bruton’s tyrosine kinase inhibitors (BTKis) acquired lisaftoclax monotherapy; Group B: lisaftoclax Mixed with ibrutinib to deal with sufferers with newly handled WM; Group C: lisaftoclax mixed with rituximab to deal with sufferers with relapsed/refractory WM who haven’t acquired BTKi remedy.
- Lisaftoclax is taken orally as soon as each day in a 28-day cycle. Lisaftoclax is titrated from a beginning dose of 400 mg to 1,200 mg. as
January 25, 2024 a complete of 46 sufferers participated within the examine (Group A [n=14] Doses as much as 1,000 mg; Arm B [n=24] Doses as much as 1,200 mg; C arm [n=8] Doses as much as 800 mg).
Efficacy outcomes:
- The median remedy period (vary) was 11 (1-28), 23.5 (1-34), and 11.5 (5-33) months in arms A, B, and C, respectively.
- ORR (PR, excellent partial response [VGPR]CR in teams A, B, and C) have been 41.7%, 90.9%, and 37.5%, respectively.
- In group A, wild-type sufferers CXCR4 (n =7) total response to lisaftoclax was higher than CXCR4 Mutant group (n = 3).
- In teams B and C, there have been no important variations between sufferers who acquired/didn’t obtain remedy. CXCR4 Mutations noticed.
security consequence:
- In Arm B, 1 dose-limiting toxicity (DLT, Grade 3 medical TLS) occurred on the 1,200 mg dose within the setting of anticipated renal impairment; 1 Grade 3 laboratory TLS occurred at 1,000 mg, primarily attributable to For the remedy of dehydration and accompanying signs. The electrolyte abnormality resolved someday after stopping the drug and didn’t recur.
- Grade ≥3 lisaftoclax-related AEs included neutropenia (15.2%), thrombocytopenia (4.3%), leukopenia (4.3%), TLS (4.3%), anemia (2.2%), weight reduction (2.2%), and Septic shock (neutropenia 2.2%).
- No ventricular arrhythmias have been noticed.
- One affected person required dose discount because of neutropenia.
- The utmost tolerated dose (MTD) was not reached.
- The PK publicity of lisaftoclax mixed with ibrutinib was corresponding to lisaftoclax or ibrutinib alone, displaying no potential DDI.
in conclusion: Lisaftoclax was properly tolerated and confirmed measurable results, both alone or together with ibrutinib or rituximab, in sufferers with WM who have been untreated or had failed BTKi remedy.
Lisaftoclax is an investigational drug and has not been authorised in any nation.
Appendix: 4 medical research Ascentage Pharma Three drug candidates, together with lisaftoclax, have been introduced at this yr’s ASCO annual assembly.
|
drug candidate |
summary title |
Summary# |
Format |
|
Ovelumbatinib |
Up to date efficacy outcomes of olverembatinib (HQP1351) in sufferers with tyrosine kinase inhibitor (TKI)-resistant succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GIST) and paraganglioma. |
Chapter 11502 |
oral Report |
|
Lishavk (APG-2575) |
Security and efficacy of lisaftoclax (a novel BCL-2 inhibitor) together with azacitidine in sufferers with treatment-naïve or relapsed or refractory acute myeloid leukemia. |
Chapter 6541 |
poster |
|
Up to date efficacy and security outcomes of the BCL-2 inhibitor lisaftoclax (APG-2575) alone or together with ibrutinib or rituximab in sufferers (pts) with Waldenstrom’s macroglobulinemia (WM). |
Chapter 7078 |
poster |
|
|
APG-2449 |
Newest examine outcomes of the novel FAK/ALK/ROS1 inhibitor APG-2449 in sufferers with non-small cell lung most cancers (NSCLC) who’re immune to second-generation ALK inhibitors. |
Chapter 3124 |
poster |
about Ascentage Pharma
Ascentage Pharma (6855.HK) is a globally targeted biopharmaceutical firm devoted to creating new remedies for most cancers, continual hepatitis B and age-related ailments. exist
Ascentage Pharma Focuses on creating therapies that inhibit protein-protein interactions to revive apoptosis, or programmed cell demise. The corporate has established a pipeline of 9 medical candidates, together with novel, extremely potent Bcl-2 and twin Bcl-2/Bcl-xL inhibitors, in addition to candidates concentrating on the IAP and MDM2-p53 pathways, in addition to next-generation tyrosine Acid kinase inhibitors (TKIs). Ascentage Pharma It’s also the one firm on the earth with energetic medical packages concentrating on all three courses of recognized key regulators of apoptosis. The corporate is conducting greater than 40 Section I/II medical trials in the USA, together with 5 world registration Section III research.
Olverembatinib is the corporate’s core drug candidate developed for the remedy of drug-resistant continual myelogenous leukemia (CML) and is the corporate’s first authorised product
With its sturdy R&D capabilities, Ascentage Pharma Established a world mental property portfolio and established world partnerships with quite a few well-known biotech and pharmaceutical firms and analysis establishments, akin to UNITY Biotechnology, MD Anderson Most cancers Heart, mayo clinic, Dana-Farber Most cancers Institute, Merck & Co. and AstraZeneca (Nasdaq: ). The corporate has constructed a gifted group with world expertise in revolutionary drug discovery and growth and is constructing world-class business manufacturing and gross sales and advertising and marketing groups. One of many key targets is Ascentage Pharma Constantly improve analysis and growth capabilities and speed up medical growth packages to meet our mission of fixing unmet medical wants
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