NDA for Parsaclisib Receives FDA Priority Review in MCL and MZL

The FDA has accepted and granted priority review to a new drug application for parsaclisib (INCB050465) for patients with relapsed/refractory mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL), according to a press release by developer Incyte. Additionally, an indication for follicular lymphoma is also under standard review.

The accepted application for the next-generation oral inhibitor of PI3Kδ comes from the results of several phase 2 studies including CITADEL-203 (NCT03126019), which examined the drug in follicular lymphoma; CITADEL-204 (NCT03144674) in MZL; and CITADEL-205 (NCT03235544) in MCL. As the priority review designation shortens the review period by 4 months vs the standard review process, the prescription drug user fee act of April 30, 2022 in MCL and MZL.

"Non-Hodgkin lymphomas are some of the most common cancers in the United States, and the FDA’s acceptance of this NDA [new drug application] represents an important milestone for Incyte and for non-Hodgkin lymphoma patients who have not responded to or who have progressed on initial therapies," Peter Langmuir, MD, group vice president of oncology targeted therapies at Incyte, said in a press release.

The primary end points for all 3 trials were objective response rate (ORR), with secondary end points including duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, and tolerability.

Results from the trials were presented at the 2020 American Society of Hematology. Patients received parsaclisib at 20 mg once daily for 8 weeks followed by either 20 mg once weekly or 2.5 mg once daily. Investigators identified that the daily dosing was the preferred method, and those who were on the weekly regimen were allowed to switch over.

Patients who enrolled on the CITADEL-203 trial had follicular lymphoma of grade 1, 2, or 3a, who received at least 2 prior lines of systemic therapy, and had an ECOG performance status of less than 2, as well as being eligible for a hematopoietic stem cell transplant. Patients in the CITADEL-204 study had MZL and received at least 1 prior systemic therapy, including Bruton tyrosine kinase (BTK) inhibitors, had a radiological measurable lymphadenopathy or extra nodal lymphoid malignancy, and an ECOG performance status of less than 2. Those in the CITADEL-205 study had relapsed/refractory MCL and received 1 to 3 prior lines of systemic therapy and were either naïve to or previously treated with a BTK inhibitor. Patients enrolled on the trial also had an ECOG score of less than 2 and radiologically measurable lymphadenopathy or an extranodal lymphoid malignancy

Those who enrolled on the CITADEL-203 trial (n = 95) and were in the daily dosing group had an ORR of 75% (95% CI, 65%-83%), a median DOR of 14.7 months (95% CI, 12.0-17.5), and a median PFS of 15.8 months (95% CI, 13.8-19.1). Comparatively, the overall patient population of 118 patients had an ORR of 73% (95% CI, 64%-81%), a median DOR of 15.9 months (95% CI, 12.0–not evaluable [NE]), and a median PFS of 15.8 months (95% CI, 13.2-19.3).

In the CITADEL-204 study, 72 patients in the daily dosing group achieved an ORR of 56.9% (95% CI, 44.7%-68.6%). The median DOR (95% CI, 8.1-NE) and median PFS (11.0-NE) were not reached. In comparison, the overall population (n = 100) had an ORR of 57.0 months (95% CI, 46.7-66.9), a median DOR of 12.0 months (5% CI, 9.3-NE), and a median PFS of 19.4 (95% CI, 13.7-NE).

In the CITADEL-205 study, 77 patients who were BTK inhibitor naïve in the daily dosing group had an ORR of 71% (95% CI, 60%-81%), a median DOR of 9.0 months (95% CI, 6.1-14.7), and a median PFS of 11.1 months (95% CI, 8.3-NE). The median OS that was not reached. Those in the overall population (n = 108) had an ORR of 70% (95% CI, 61%-79%), a median DOR of 14.7 months (95% CI, 7.7-NE), and a median PFS of 11.1 months (95% CI, 8.3-19.2). The median OS that was not reached.

Additionally, those in the CITADEl-205 trial who were previously treated with ibrutinib (Imbruvica) in the daily dosing group (n = 41) had an ORR of 29% (95% CI, 16%-46%), a median DOR of 3.7 months (95% CI, 1.9-NE), a median PFS of 3.7 months (95% CI, 1.8-4.1), and a median OS of 11.2 months (7.9-NE). Additionally, those in the overall population (n = 53) had an ORR of 25% (95% CI, 14%-38%), a median DOR of 3.7 months (95% CI, 1.9-NE), a median PFS of 3.7 months (95% CI, 1.8-3.9), and a median OS of 11.2 months (95% CI, 7.9-17.1).

Parsaclisib has previously been granted priority review by the FDA for the treatment of relapsed or refractory MZL for those who have received at least 1 prior line of an anti–CD20-based regimen. It was also granted priority review for patients with MCL who have had at least 1 prior line of therapy.

Currently, confirmatory phase 3 studies being prepared to further assess the use of parsaclisib in patients with MCL (CITADEL-301), and relapsed or refractory follicular lymphoma and MZL (CITADEL-302).

References

1. Incyte announces acceptance of NDA for parsaclisib for three types of relapsed or refractory non-Hodgkin lymphomas. News Release. Incyte. November 1, 2021. Accessed November 1, 2021. https://yhoo.it/3w3rz05

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. December 7, 2020. Accessed November 1, 2021. https://bwnews.pr/3ECPgPI