Imbruvica plus Venclexta Fixed-Duration Regimen Demonstrates Superior Progression-Free Survival Over Chlorambucil Plus Obinutuzumab in First-Line CLL Treatment
Jun 18, 2021 02:46
CST Updated
02:46
AbbVie
Innovative Drug Developer
`Chronic lymphocytes`Leukemia(CLL, Image source: dxline.info)
June 17, 2021 News /BioValleyBIOON/ -- AbbVie recently announced new data from the Phase 3 GLOW study (NCT03462719). The study enrolled patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had active disease requiring treatment according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria. The study is evaluating the efficacy and safety of a first-line regimen combining Imbruvica® (ibrutinib) and Venclexta® (venetoclax) (I+V), and comparing it with the standard-of-care chemoimmunotherapy regimen of chlorambucil plus obinutuzumab (C+O).I+V is an all-oral, once-daily, chemotherapy-free, fixed-duration (FD) combination therapy.
The results show,The study met the primary endpoint of progression-free survival (PFS) assessed by the Independent Review Committee (IRC) (HR=0.216; 95% CI: 0.131-0.357)., indicatingThe I+V regimen reduced the risk of disease progression or death by approximately 78% compared with the C+O regimen.The benefit of I+V on PFS was consistent across prespecified subgroups, including patients aged ≥65 years and those with comorbidities (CIRS >6). The median PFS was 21 months in the C+O group, whereas the median PFS in the I+V group had not been reached at the time of analysis.
Secondary endpoints include undetectable minimal residual disease (uMRD, i.e., MRD-negative [MRD-]), complete response rate (CR), and overall response rate (ORR). Assessed by next-generation sequencing,The bone marrow uMRD rate in the I+V group was significantly higher than that in the C+O group (p<0.0001). Three months after treatment completion, the uMRD rates were 51.9% and 17.1%, respectively.49% of patients in the I+V group and 12% of patients in the C+O group sustained peripheral blood (PB) uMRD for 12 months after treatment completion.The CR rate in the I+V group was significantly higher than that in the C+O group (38.7% vs 11.4%; p<0.0001).. There was no significant difference in ORR between the I+V group and the C+O group.Delayed time to subsequent therapy in the I+V group compared with the C+O group (HR=0.143, 95% CI: 0.05-0.41). The safety profile of I+V is generally consistent with that of each drug in the regimen, and its tolerability is consistent with CLL treatment in the enrolled patient population.
Dr. Arnon Kater, Deputy Head of the Department of Hematology at Amsterdam University Medical Center, stated: “CLL is one of the most common types of blood cancer, and expanding research into additional treatment options is a critical clinical priority. The progression-free survival results for the I+V regimen in the GLOW study are highly promising, demonstrating the potential of this regimen as an additional treatment option for the CLL patient population.”
AbbVie Vice President and GlobalTumorDr. Mohamed Zaki, Head of Development, stated: “We are encouraged by these results, which further support the efficacy of these two established therapies. We remain firmly committed to continuing the research and development of this combination therapy as a potential treatment for CLL, with the ultimate goal of enabling patients to achieve remission with a fixed-duration oral regimen.”
ibrutinib is the world's first marketed BTK inhibitor, receiving its initial approval in November 2013. The drug was co-developed and commercialized by Pharmacyclics, an AbbVie company, and Janssen Pharmaceuticals, a Johnson & Johnson company. AbbVie holds the rights to the U.S. market, while Johnson & Johnson holds the rights for markets outside the U.S. BTK is a kinase essential for B-cell survival. By inhibiting BTK, ibrutinib helps force malignant B cells out of their growth and proliferation microenvironments, such as lymph nodes, and prevents their return. The action of ibrutinib, in conjunction with other effects of BTK inhibition, reduces the survival capacity of malignant B cells.
ibrutinib has been approved in over 100 countries and has treated more than 230,000 patients worldwide to date. ibrutinib is the only one in 3 CLLClinical TrialAmong BTK inhibitors demonstrating overall survival (OS) benefits, remission lasts up to 8 years, with 70% of patients remaining alive and progression-free at 5 years. Furthermore, ibrutinib is the only BTK inhibitor proven to modulate both short- and long-term immune recovery.
In China, ibrutinib (IMBRUVICA®) was first approved in August 2017., as a monotherapy, for the treatment of: (1) patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have received at least one prior therapy; (2) patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. In November 2018, Imbruvica was approved for new indications: (1) as a monotherapy, for the treatment of patients with Waldenström's macroglobulinemia (WM) who have received at least one prior therapy, or as first-line therapy for patients who are not suitable for chemoimmunotherapy; (2) in combination with rituximab, for the treatment of patients with WM.
Venetoclax is a first-in-class, oral, selective B-cell lymphoma-2 (BCL-2) inhibitor co-developed by AbbVie and Roche, with both companies jointly responsible for commercialization in the US market (trade name: Venclexta), while AbbVie is responsible for commercialization outside the US (trade name: Venclyxto). The BCL-2 protein inApoptosisplays an important role in (programmed cell death), prevents apoptosis in certain cells (including lymphocytes), and is overexpressed in certain types of cancer, which is associated with the development of drug resistance. Venetoclax is designed to selectively inhibit the function of BCL-2, restore cellular communication systems, and induce cancer cells to self-destruct, thereby achieving therapeuticTumorpurpose.
Venetoclax has been approved in more than 80 countries worldwide for the treatment of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and acute myeloid leukemia (AML). In the United States, venetoclax has beenFDAGranted 5 Breakthrough Therapy Designations (BTD), one for first-line treatment of CLL, two for relapsed or refractory CLL, and two for first-line treatment of acute myeloid leukemia (AML).
In China, venetoclax (Venclexta®, venetoclax) was approved in December 2020., in combination with azacitidine, for the treatment of patients who are ineligible for intensive induction chemotherapy due to comorbidities, or who are aged 75 years and older, with newlyDiagnosisadult patients with acute myeloid leukemia (AML). Venetoclax (Venclexta®, venetoclax) is the first approved B-cell lymphoma-2 (BCL-2) inhibitor in China, marking the entry of China's AML field into the era of targeted therapy. (Bioon.com)