FDA Approval Sought for Parsaclisib in 3 Types of Relapsed/Refractory Non-Hodgkin Lymphoma

The FDA has accepted a new drug application (NDA) for the PI3Kδ inhibitorparsaclisib for use in the treatment of patients with relapsed or refractory follicular lymphoma, marginal zone lymphoma, and mantle cell lymphoma.¹

The application is supported by findings from several phase 2 trials. Eligible participants received parsaclisib at a once-daily dose of 20 mg for the duration of 8 weeks followed by either 20 mg once weekly or a once-daily dose of 2.5 mg (daily-dosing group [DG]). Daily dosing was selected as the preferred regimen and participants were able to switch to DG.

The primary end point of the trial was ORR; key secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, and tolerability.

Results from the CITADEL-203 trial (NCT03126019), which is examining the agent in relapsed or refractory follicular lymphoma, parsaclisib elicited an objective response rate (ORR) of 73% (95% CI, 64%-81%) in all 118 patients.² Data from the CITADEL-204 trial (NCT03144674), which is examining parsaclisib in those with marginal zone lymphoma (MZL), demonstrated an ORR of 57% (95% CI, 46.7%-66.9%) in 100 patients.

Additionally, findings from the CITADEL-205 (NCT03235544) trial, which is evaluating the agent in patients with relapsed/refractory mantle cell lymphoma (MCL), showed that parsaclisib elicited an ORR of 70% (95% CI, 61%-79%) among 108 patients who were naïve to BTK inhibitors, and 25% (95% CI, 14%-38%) among 53 patients who previously received ibrutinib (Imbruvica).

Across the studies, parsaclisib has been found to be well tolerated with a manageable toxicity profile.

“Non-Hodgkin lymphomas are some of the most common cancers in the United States, and the FDA’s acceptance of this NDA represents an important milestone for Incyte and for [patients with this disease] who have not responded to, or who have progressed on initial therapies,” Peter Langmuir, MD, group vice president of Oncology Targeted Therapies at Incyte, stated in a press release. “We look forward to working with the FDA to bring this innovative therapy to patients who may benefit.”

CITADEL-203 enrolled patients with relapsed/refractory follicular lymphoma who had grade 1, 2, or 3a disease and who previously received at least 2 systemic therapies, had an ECOG performance status of 0 to 2, and were ineligible to under hematopoietic stem cell transplantation.

Additional data presented during the 2020 ASH Annual Meeting showed that the median duration of response (DOR) with parsaclisib was 15.9 months (95% CI, 12.0–not evaluable [NE]), and the median progression-free survival (PFS) was 15.8 months (95% CI, 13.2-19.3).

Among the 95 patients who comprised the DG group, the ORR with parsaclisib was 75% (95% CI, 65%-83%), the median DOR was 14.7 months (95% CI, 12.0-17.5), and the median PFS was 15.8 months (95% CI, 13.8-19.1).

CITADEL-204 enrolled those with MZL who previously received at least 1 systemic therapy. Patients needed to be naïve to BTK inhibitors. Although patients who previously received ibrutinib were permitted, the cohort was terminated because of slow enrollment. Other eligibility criteria included radiologically measurable lymphadenopathy or extranodal lymphoid malignancy and an ECOG performance status of 0 to 2.

Additional data showed that among the 72 patients who comprised the DG group, the ORR achieved with parsaclisib was 56.9% (95% CI, 44.7%-68.6%), the median DOR had not yet been reached (95% CI, 8.1–NE), and the median PFS had also not been reached (95% CI, 11.0–NE).

CITADEL-205 enrolled patients with relapsed or refractory MCL who previously received 1 to 3 systemic therapies and were either naïve to, or were previously treated with, a BTK inhibitor. Patients needed to have an ECOG performance status of 0 to 2 and radiologically measurable lymphadenopathy or extranodal lymphoid malignancy.

Among the 77 patients who were BTK inhibitor naïve and comprised the DG group, the ORR achieved with parsaclisib was 71% 95% CI, 60%-81%), the median DOR was 9.0 months (95% CI, 6.7-14.7), and the median PFS was 11.1 months (95% CI, 8.3­–NE), and the median OS had not yet been reached (NE–NE). Among the 41 patients who were previously treated with ibrutinib and comprised the DG group, the median ORR was 29% (95% CI, 16%-46%), the median DOR was 3.7 months (95% CI, 1.9–NE), the median PFS was 3.7 months (95% CI, 1.8-4.1), and the median OS was 11.2 months (95% CI, 7.9–NE).

Parsaclisib was granted priority review from the regulatory agency for the treatment of adult patients with relapsed or refractory MZL who previously received at least 1 anti–CD20-based regimen and for adult patients with MCL who have previously received at least 1 therapy. The FDA is expected to decide on these 2 applications by April 30, 2022, under the Prescription Drug User Fee Act.

The NDA for parsaclisib in adult patients with relapsed or refractory follicular lymphoma who have previously received at least 2 prior therapies has a target action date of August 30, 2022.

Moreover, the confirmatory phase 3 CITADEL-310 trial (NCT04849715) examining parsaclisib in combination with bendamustine and rituximab (Rituxan) in newly diagnosed patients with MCL, and the phase 3 CITADEL-302 trial examining parsaclisib plus either rituximab or obinutuzumab (Gazyva) in patients with relapsed/refractory follicular lymphoma and MZL, are underway.

References

1. Incyte announces acceptance of NDA for parsaclisib for three types of relapsed or refractory non-Hodgkin lymphomas. News release. Incyte Corporation. November 1, 2021. Accessed November 1, 2021. https://bit.ly/3nN3OFL
2. Incyte announces parsaclisib treatment results in high rate of rapid and durable responses in patients with relapsed or refractory B-cell non-Hodgkin lymphomas. News release. Incyte Corporation. December 7, 2020. Accessed November 1, 2021. https://bwnews.pr/3BB7OOC