CELESTIAL-TNCLL: AN ONGOING, OPEN-LABEL, MULTIREGIONAL, PHASE 3 STUDY of SONROTOCLAX (BGB-11417) + ZANUBRUTINIB VS VENETOCLAX + OBINUTUZUMAB for TREATMENT-NAIVE (TN) CLL.
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All Authors
Patten, P.
Kater, A.P.
Woyach, J.
Li, J.
Munir, T.
Salmi, T.
Phuong, P.
Tian, T.
Shadman, M.
LTHT Author
Munir, Talha
LTHT Department
Oncology
Haematology
Haematology
Non Medic
Publication Date
2024
Item Type
Conference Abstract
Language
Subject
ADULT , APOPTOSIS , WOMEN , FOLLOW-UP-STUDIES , NEOPLASM, RESIDUAL , MAGNETIC RESONANCE IMAGING , MULTICENTRE STUDIES AS TOPIC , NEUTROPHILS , SURVIVAL RATE , OUTCOME ASSESSMENT , CLINICAL TRIALS AS TOPIC , DISEASE-FREE SURVIVAL , RANDOMISED CONTROLLED TRIAL , DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS , ANTINEOPLASTIC AGENTS , ANTIBODIES, MONOCLONAL
Subject Headings
Abstract
Background: The combination of venetoclax (ven), the first-generation BCL2 apoptosis regulator (BCL2) inhibitor, and ibrutinib, a BTK inhibitor, has demonstrated efficacy in patients with CLL (Wierda et al. J Clin Oncol. 2021). However, the toxicity profile of this regimen suggests a need for a more tolerable combination of BTK and BCL2 inhibitors. Sonrotoclax, a next-generation BCL2 inhibitor, is a more selective and more pharmacologically potent inhibitor of BCL2 than ven. Zanubrutinib, a nextgeneration BTK inhibitor, significantly improved PFS and had a more tolerable safety profile, including fewer cardiac adverse events, vs ibrutinib in a randomized, head-to-head study of patients with CLL/SLL (Brown et al. N Engl J Med. 2023). In a phase 1 study in patients with TN CLL treated with sonrotoclax + zanubrutinib, efficacy data was promising, with ORR and 1-year progression-free survival (PFS) rate of 100% and deep responses on the basis of undetectable measurable residual disease at <10-4 sensitivity (uMRD4). The most common grade >=3 TEAE was neutropenia, and no tumor lysis syndrome or cardiac toxicity was observed (Tam et al. Blood. 2023). Presented here is the design of a phase 3 trial aimed at comparing the efficacy of sonrotoclax + zanubrutinib vs ven + obinutuzumab (obi) in patients with TN CLL. Aim(s): N/A Methods: CELESTIAL-TNCLL (BGB-11417-301; NCT06073821) is a randomized, open-label, phase 3 study. Eligible patients must have previously untreated CLL that requires treatment per 2018 iwCLL criteria, measurable disease by CT/MRI, an ECOG performance score of 0 to 2, and adequate hematologic and organ function. Approximately 640 patients will be randomized 1:1 to receive either three cycles of oral zanubrutinib monotherapy (320 mg daily) followed by zanubrutinib + sonrotoclax for 12 cycles, or standard ven + obi treatment for 12 cycles. Randomization will be stratified by age (<65 vs >=65 years) and IGHV and del(17p)/TP53 mutation status. The primary endpoint is PFS as assessed by independent review committee (IRC) according to 2018 iwCLL guidelines, with modifications for treatment-related lymphocytosis in patients with CLL (Cheson et al. J Clin Oncol. 2012). Key secondary endpoints include complete response rate (CRR), defined as CR or CR with incomplete hematopoietic recovery, assessed by IRC; rates of uMRD4 in bone marrow and peripheral blood at the first posttreatment follow-up visit based on next-generation sequencing by clonoSEQ (Adaptive Biotechnologies, Seattle, W); and overall survival. Other secondary endpoints include PFS as assessed by investigator (INV); CRR by INV; rate of uMRD4 based on flow cytometry; overall esponse rate by IRC and INV; duration of response by IRC and INV; patient-reported outcomes; and safety and tolerability. Recruitment is ongoing. Result(s): N/A Smmary/Conclusion: N/A.
Journal
HemaSphere