Parsaclisib Demonstrated Durable Responses, Manageable Safety for Patients With R/R Marginal Zone Lymphoma

Phase 2 Results from the CITADEL-204 Study

Durable responses and an overall manageable safety profile were demonstrated among patients with relapsed/refractory (R/R) marginal zone lymphoma (MZL) treated with parsaclisib, a highly selective, potent PI3Kδ inhibitor, monotherapy, according to phase 2 results from the CITADEL-204 study.

Eligible patients included those aged ≥18 years with histologically confirmed R/R MZL, treated with ≥1 prior systemic therapy (including ≥1 anti-CD20 antibody). Patients received parsaclisib, 20 mg once daily for 8 weeks then 20 mg once weekly (weekly dosing group [WG]) or parsaclisib 20 mg once daily for 8 weeks then 2.5 mg once daily (daily dosing group [DG]). The noted primary end point of this trial was the independent review committee (IRC)–determined overall response rate (ORR), which was assessed by CT or MRI according to Lugano classification response criteria for lymphomas.

 Investigators evaluated the efficacy and safety of parsaclisib in Bruton tyrosine kinase (BTK) inhibitor–experienced, labeled as cohort 1, or BTK inhibitor–naive, labeled as cohort 2, patients with R/R MZL. Due to slow recruitment, cohort 1 closed with 10 patients (WG, n = 4; DG, n = 6) who enrolled. At the data cutoff of January 15, 2021, 100 patients were enrolled and treated in cohort 2 (WG, n = 28; DG, n = 72).

Trial results demonstrated that in the DG, the ORR was 58.3% (95% confidence interval [CI], 46.1 to 69.8), with a complete response rate (CRR) of 4.2% (95% CI, 0.9 to 11.7). It was noted that the lower bound of the ORR 95% CI exceeded the protocol-defined threshold of 40%. Additionally, the median duration of response was 12.2 months (95% CI, 8.1 to 17.5) and progression-free survival (PFS) was 16.5 months (95% CI, 11.5 to 20.6). The median overall survival was not reached.

The most notable and common treatment-emergent adverse events (TEAEs) among all patients were diarrhea (47%), cough (23%), and rash (18%). The most common grade ≥3 TEAEs included diarrhea (12%), neutropenia, and pneumonia (9% each). Furthermore, TEAEs led to dose interruptions, reductions, and discontinuations in 56%, 16%, and 29% of all patients, respectively.

Tycel J. Phillips, MD, Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan, and colleagues concluded, “Parsaclisib demonstrated a durable response with a safety profile consistent with PI3K inhibitor treatment in patients with R/R MZL.”

“Although parsaclisib demonstrated meaningful clinical benefit and an overall manageable safety profile in patients with R/R MZL in this study, a new study will be required to further test the hypothesis that reduction of certain side effects, such as diarrhea and colitis, could be achieved with a [once weekly] maintenance dosing schedule, with minimal impact on efficacy,” the study authors noted, adding that no such further studies are planned at this time. 

Source:

Phillips T, Avigdor A, Gurion R, et al. A phase 2 study of the PI3Kδ inhibitor parsaclisib in relapsed and refractory marginal zone lymphoma (CITADEL-204). Blood Adv (2024) 8 (4): 867–877. doi: 10.1182/bloodadvances.2023010648