A phase Ib study of a PI3Kδ inhibitor Linperlisib in patients with relapsed or refractory peripheral T-cell lymphoma.

Abstract

7531 Background: PI3Kδ inhibitors have been shown to have important roles in blocking mitogenic and survival signaling within the tumor cell and the tumor microenvironment and activate antilymphoma immune responses. Linperlisib is an oral highly selective small molecule inhibitor of PI3Kδ and has been demonstrated to be well-tolerated with a favorable PK profile in patients with lymphomas at the RP2D. This phase Ib study is evaluating the efficacy and safety of Linperlisib in relapsed or refractory peripheral T-cell lymphoma (PTCL), a highly aggressive malignancy with few treatment options for patients. Methods: Eligible PTCL patients who must have received at least 1 prior systemic conventional therapy were administrated Linperlisib 80mg orally once daily (RP2D) in 28 days cycle until disease progression, unacceptable toxicity, or withdrawal from the study. Tumor response was assessed by IWG 2007 criteria with CT performed every 2 cycles. The primary endpoint was the overall response rate (ORR), and the secondary endpoint was toxicity assessed by NCI-CTCAE5.0. Results: As of February 2, 2021, 36 PTCL patients were enrolled in this exploratory trial. Most patients were stage III (38.2%) or IV (50%). Of the 27 evaluable patients to date, the PTCL histologies were PTCL-NOS (n=12), AITL (n=10), ALCL (n=3), NKTCL (n=1) and MEITL (n=1). 19 of the 27 evaluable patients had Investigator confirmed responses for a 70.4% ORR including 25.9% CR (7pt) and 44.4% PR (12pt). In the major subtypes, ORR was 50% (6/12) PTCL-NOS and 80% (8/10) AITL, respectively. A disease control rate of 100% was observed, and most responses occurred by first assessment at C2D28. One subject who had a CR at C2D28 is currently in cycle 9 and continuing on Linperlisib. 36 patients experienced at least 1 AE in the trial, with 95% of AEs ≤ grade 2. Consistent with previously treated lymphoma patients, no unexpected toxicities were observed. The most common TRAEs (≥10%) were neutrophil count decreased (55.6%), leukocyte count decreased (33.3%), hypertriglyceridemia (22.2%), aspartate aminotransferase increased (16.7%), hypercholesterolemia (16.7%), alanine aminotransferase increased (11.1%), creatinine increased (11.1%), rash (11.1%), thrombocyte count decreased (11.1%) and electrocardiogram T wave abnormal (11.1%). No AE grade 4 was observed. 6 patients (16.7%) experienced at least one SAE, in which 4 (11.1%) SAEs were considered to be drug-related, including neutrophil count and leukocyte count decreased (2.8%), gastritis (2.8%), and pneumonia (5.6%). Conclusions: The oral PI3Kd inhibitor Linperlisib had significant activity in patients with relapsed or refractory PTCL. Toxicities with Linperlisib therapy were generally tolerable and manageable. Further efficacy and safety is being evaluated. Clinical trial information: NCT04108325.