The combination of zandelisib and zanubrutinib produces high overall response rates (ORRs) in patients with relapsed/refractory follicular lymphoma (FL) or mantle cell lymphoma (MCL), according to a study presented at the 2022 ASH Annual Meeting.1
Intermittent dosing of zandelisib in combination with twice-daily zanubrutinib produced an ORR of 86.7% in patients with FL and an ORR of 72.2% in patients with MCL.
This phase 1b trial (ClinicalTrials.gov Identifier: NCT02914938) enrolled 31 patients with FL. Their median age was 69 (range, 40-83) years, and 54.8% were men. They had received a median of 2 prior lines of therapy (range, 1-5), and 29.0% had tumor bulk of 50 mm or greater.
The trial enrolled 19 patients with MCL. Their median age was 65 (range, 52-78) years, and 73.7% were men. They had received a median of 1.5 prior lines of therapy (range 1-3), and 26.3% had tumor bulk of 50 mm or greater.
In both cohorts, patients received zandelisib at 60 mg daily on days 1-7 of each 28-day cycle. Zanubrutinib was given at 80 mg twice daily every day. Patients were treated until disease progression or intolerance.
In the FL cohort, the median follow-up was 13.5 months. The ORR was 86.7%, the complete response (CR) rate was 23.3%, and the partial response (PR) rate was 63.3%. The median duration of response was 20.6 months, and the median progression-free survival (PFS) was 22.4 months.
In the MCL cohort, the median follow-up was 7.4 months. The ORR was 72.2%, the CR rate was 8%, and the PR rate was 44.4%. The median duration of response was not reached, and the median PFS was 10.1 months.
The most common adverse events in all patients were diarrhea, neutrophil count decrease, platelet count decrease, blood creatinine increase, and anemia.
The most common severe adverse events were grade 4 neutrophil count decrease (12%), grade 3 neutrophil count decrease (8%), and grade 3 alanine transferase increase (8%).
Two patients discontinued treatment due to treatment-related adverse events. One was neutrophil count decrease, and 1 was drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome.
One patient with MCL died from COVID-19-related complications.
Though the study investigators concluded that these results support further evaluation of this combination, MEI Pharma and Kyowa Kirin recently announced that they will no longer be developing zandelisib outside of Japan.2
Disclosures: This research is supported by MEI Pharma, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
1. Soumerai JD, Diefenbach CS, Samaniego F, et al. Safety and efficacy of the PI3Kδ inhibitor zandelisib combination with the BTK inhibitor zanubrutinib in patients with relapsed/refractory (r/r) follicular lymphoma (FL) or mantle cell lymphoma (MCL). Presented at ASH 2022. December 10-13, 2022. Abstract 78.
2. MEI Pharma and Kyowa Kirin announce discontinuation of zandelisib development outside of japan following recent FDA meeting. Business Wire. News release. Published December 5, 2022. Accessed December 11, 2022.