PI3K δ plays an essential role in B-cell development and function. And SHC014748M is a small-molecule inhibitor of PI3K with high selectivity to δ isoform. Thus, we evaluated the safety, tolerability, efficacy and pharmacokinetics of SHC014748M capsules in patients with relapsed or refractory inert B-cell malignancies in this study.
This trial included two phases: dose-escalation phase and dose-expansion phase. 3 subjects with iNHL(indolent non-Hodgkin Lymphoma) were respectively assigned into five dose levels (50-250mg). 12 patients were enrolled in the 150mg QD and 12 in the 200mg QD. The primary outcomes were safety, tolerability, and pharmacokinetics of SHC014748M Capsules in Patients. The secondary outcome was ORR (Overall Response Rate).
39 patients were enrolled in the study, including 23(59.0%) with follicular lymphoma, 11 (28.2%) with chronic lympho cytic leukemia/small lymphocytic lymphoma, 2 (5.1%) with Marginal Zone Lymphoma, and 3 (7.7%) with Waldenstrom Macroglobulinemia. The median age was 55 and 30 were males. The mean lines of prior systemic therapy was 2.23. Dose Limited Toxicity did not occur in all dose groups. Common adverse events included neutropenia (45.5%), blood lactate dehydrogenase increased (38.2%), platelet count decreased (25.5%), anemia (21.8%) and fatigue (23.6%). Severe (Grade≥3) adverse reaction included neutropenia (16.4%), diarrhea (7.3%) , pneumonitis (5.5%), rash (5.5%) and anemia (5.5.%). Tmax was 1.3 ∼ 2.2 h and T1/2 was 14.1 ∼ 22.1 h after taking orally SHC014748M capsule for 28 days. The overall ORR across all groups (50-250 mg QD) was 59.0%, with 66.7% (CR 6.7%, PR 60.0%) in 200 mg QD. For patients with follicular lymphoma, the ORR reached at 72.7% (CR 9.0%, PR 63.7%) in 200mg QD.
Oral administration of SHC014748M capsules in Patients with iNHL were highly effective and safe in Chinese patients. And the results of phase I study suggested patients with FL administered at 200mg should be explored in additional studies.
Clinical trial identification
Legal entity responsible for the study
Nanjing Sanhome Pharmaceutical CO., LTD.
All authors have declared no conflicts of interest.