KEY TAKEAWAYS
- The CITADEL-204 phase II trial aimed to evaluate parsaclisib’s efficacy and safety in BTK inhibitor-experienced and -naive patients with R/R MZL patients.
- The primary endpoint was ORR.
- Parsaclisib monotherapy exhibited lasting responses and maintained a generally safe profile in R/R MZL patients.
Dr. Tycel Phillips and his team spearheaded the study that aimed to investigate parsaclisib’s efficacy and safety in patients with relapsed/refractory(R/R) marginal zone lymphoma (MZL), stratified by prior Bruton tyrosine kinase inhibitor exposure.
Patients aged 18 years and older with histologically confirmed R/R MZL, previously treated with at least one systemic therapy (including at least one anti-CD20 antibody), were administered either parsaclisib 20 mg once daily for 8 weeks followed by 20 mg once weekly (weekly dosing group [WG]) or parsaclisib 20 mg once daily for 8 weeks followed by 2.5 mg once daily (daily dosing group [DG]). The DG was chosen for further evaluation.
The results demonstrated that in cohort 2, comprising 100 enrolled and treated patients (WG, n = 28; DG, n = 72), the ORR in the DG was 58.3% (95% CI, 46.1-69.8), surpassing the protocol-defined threshold of 40%. Notably, the complete response rate was 4.2% (95% CI, 0.9-11.7). The median duration of response stood at 12.2 months (95% CI, 8.1-17.5), while progression-free survival (PFS) was 16.5 months (95% CI, 11.5-20.6), with median overall survival not yet reached.
Common treatment-emergent adverse events (TEAEs) across all patients included diarrhea (47.0%), cough (23.0%), and rash (18.0%). Grade ≥3 TEAEs, such as diarrhea (12.0%), neutropenia, and pneumonia (9.0% each), were also observed. TEAEs resulted in dose interruptions, reductions, and discontinuations in 56.0%, 16.0%, and 29.0% of all patients, respectively.
The study concluded that patients with R/R MZL treated with parsaclisib monotherapy exhibited durable responses and a manageable safety profile.
The study was sponsored by AstraZeneca and Pharmacyclics Bristol Myers Squibb, Incyte Corporation, Gilead Sciences, Novartis, Takeda, AbbVie, Amgen, Celgene, Daiichi Sankyo, F. Hoffman-La Roche Ltd, Janssen, Kyowa Kirin, Kite, Sanofi, Servier, TG Therapeutics, BeiGene, MorphoSys, Seattle Genetics, and Roche-Genentech, among others.
Source: https://pubmed.ncbi.nlm.nih.gov/38113459/
Clinical Trial: https://clinicaltrials.gov/study/NCT03144674
Phillips TJ, Avigdor A, Gurion R, et al. (2024) ‘’A phase 2 study of the PI3Kδ inhibitor parsaclisib in relapsed and refractory marginal zone lymphoma (CITADEL-204).’’ Blood Adv. 2024 Feb 27;8(4):867-877. doi: 10.1182/bloodadvances.2023010648.
